\r\n\r\n \r\n\r\nThis work has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634476 for project with acronym TREASURE. The content of this book reflects only the authors\' view and the European Union Agency is not responsible for any use that may be made of the information it contains.\r\n',isbn:"978-1-78985-408-4",printIsbn:"978-1-78985-407-7",pdfIsbn:"978-1-83962-011-9",doi:"10.5772/intechopen.83749",price:139,priceEur:155,priceUsd:179,slug:"european-local-pig-breeds-diversity-and-performance-a-study-of-project-treasure",numberOfPages:318,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"182fe65256f9a0bbc25b0b7576412b0e",bookSignature:"Marjeta Candek-Potokar and Rosa M. Nieto Linan",publishedDate:"February 6th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/9356.jpg",numberOfDownloads:22487,numberOfWosCitations:37,numberOfCrossrefCitations:33,numberOfCrossrefCitationsByBook:13,numberOfDimensionsCitations:59,numberOfDimensionsCitationsByBook:18,hasAltmetrics:1,numberOfTotalCitations:129,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 21st 2018",dateEndSecondStepPublish:"January 11th 2019",dateEndThirdStepPublish:"March 12th 2019",dateEndFourthStepPublish:"May 31st 2019",dateEndFifthStepPublish:"July 30th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:'
This work has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634476 for project with acronym TREASURE. The content of this book reflects only the authors\' view and the European Union Agency is not responsible for any use that may be made of the information it contains.
',editors:[{id:"23161",title:"Dr.",name:"Marjeta",middleName:null,surname:"Čandek-Potokar",slug:"marjeta-candek-potokar",fullName:"Marjeta Čandek-Potokar",profilePictureURL:"https://mts.intechopen.com/storage/users/23161/images/8255_n.jpg",biography:"Marjeta Čandek Potokar is a researcher at the Agricultural Institute of Slovenia. She graduated in Animal Science and has a PhD in Food Science. Her main research area is meat science. Current research topics comprise: (1) the local Krškopolje pig breed, (2) castration issues (boar taint, immunocastration, nutrition, product quality), (3) dry cured products, (4) carcass classification methods, and (5) use of NIRS for meat quality assessment. She has led seven national projects and participated in many EU projects (EUPIGCLASS, YOUNG-TRAIN, PIGCAS, TRUEFOOD, COST FAIM, COST IPEMA, ERA-NET SUSI); presently she coordinates H2020 project TREASURE. She is habilitted at the Faculty of Agriculture and Life Sciences of the University of Maribor as a lecturer of technology of animal products. She has authored over 60 SCI papers, numerous professional articles, conference contributions, and book chapters.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Agricultural institute of Slovenia",institutionURL:null,country:{name:"Slovenia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"290236",title:"Dr.",name:"Rosa",middleName:"Maria",surname:"Nieto",slug:"rosa-nieto",fullName:"Rosa Nieto",profilePictureURL:"https://mts.intechopen.com/storage/users/290236/images/8256_n.jpg",biography:"Rosa M. Nieto is a researcher at the Spanish National Research Council. She graduated in Biological Sciences and has a PhD in Animal Nutrition. Her research activity is nutrient metabolism of livestock (mainly swine), focusing on protein deposition in muscle. Over the last few years she has concentrated on Iberian pig metabolic characterization, investigating nutritional requirements (particularly amino acids and energy) during different growth phases. Her research interests include the effects of immunocastration on productivity and meat quality, links between amino acid and lipid metabolism, and consequences on meat quality. She has participated in nearly 30 research projects and contracts with international (including H2020 project TREASURE), national, and regional funding, in many of them as a research leader. She has authored over 70 SCI papers and many professional articles and congress contributions.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"297",title:"Animal Science",slug:"animal-science"}],chapters:[{id:"65254",title:"Introductory Chapter: Concept and Ambition of Project TREASURE",doi:"10.5772/intechopen.84246",slug:"introductory-chapter-concept-and-ambition-of-project-treasure",totalDownloads:1050,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:null,signatures:"Marjeta Čandek-Potokar, Luca Fontanesi, Bénédicte Lebret, José M. Gil,\nCristina Ovilo, Rosa Nieto, Ana Fernandez, Carolina Pugliese,\nMaria-Angels Oliver and Riccardo Bozzi",downloadPdfUrl:"/chapter/pdf-download/65254",previewPdfUrl:"/chapter/pdf-preview/65254",authors:[{id:"23161",title:"Dr.",name:"Marjeta",surname:"Čandek-Potokar",slug:"marjeta-candek-potokar",fullName:"Marjeta Čandek-Potokar"}],corrections:null},{id:"65363",title:"Alentejano Pig",doi:"10.5772/intechopen.83757",slug:"alentejano-pig",totalDownloads:1091,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"The present chapter presents the history and current status of Alentejano pig breed, a Portuguese autochthonous swine breed. A review of literature regarding reproductive and productive traits was carried out. Reproductive performance includes sow age at first parturition and at culling, litters per sow and per year, piglets born alive per litter, percentage of stillborn per litter, piglets birth weight, mortality rate until weaning, piglet weaned per litter, duration of lactation and farrowing interval. Growth performance includes average daily gain and average daily feed intake during lactation, early, middle and late growing stages and fattening stage. Carcass traits were evaluated using age and weight at slaughter, hot carcass weight, carcass yield, lean meat content, back fat thickness at withers and at the level of the last rib, muscle thickness at the cranial edge of gluteus medius muscle and loin eye area. Meat and fat quality traits of longissimus muscle were evaluated by means of pH at 45 min and 24 hours after slaughter, objective colour (CIE L*, a* and b*), intramuscular fat content and fatty acid composition of intramuscular fat. However, a considerable number of studies on Alentejano pig, data on reproductive performance and some parameters of meat quality are still scarce.",signatures:"Rui Charneca, José Martins, Amadeu Freitas, José Neves, José Nunes, Hugo Paixim, Pedro Bento and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65363",previewPdfUrl:"/chapter/pdf-preview/65363",authors:[{id:"290234",title:"Dr.",name:"Rui",surname:"Charneca",slug:"rui-charneca",fullName:"Rui Charneca"}],corrections:null},{id:"65352",title:"Basque Pig",doi:"10.5772/intechopen.83758",slug:"basque-pig",totalDownloads:1120,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Local pig breeds are adapted to the specific local environment and fed with various locally available feedstuffs. Besides their genetic merit for agro-biodiversity, they represent the basis for sustainable local pork chains. The present chapter aims to present history and current status of the Basque pig breed, its exterior phenotypic characteristics, geographical location, production system and main products. This French autochthonous breed of pigs, which almost disappeared few decades ago, seems now consolidated, thanks to a chain organization and recognised high-quality products (Protected Designation of Origin). Reproductive performance data reviewed from the literature and estimated from the LIGERAL database (herdbook) are presented. Available data on production traits including growth (early, middle, late and overall growth), feed intake, body composition and carcass traits are also summarized. Meat quality traits (pH, colour, intramuscular fat content and fatty acid composition) and back fat tissue characteristics (fatty acid profile) are also described. Studies on the Basque pig breed are scarce. Different production systems, feeding regimes and feed composition used among studies can explain differences observed between studies, especially for productive traits. However, the current review gives insight into the reproduction, production and carcass and meat quality traits of this local pig breed.",signatures:"Marie-José Mercat, Bénédicte Lebret, Herveline Lenoir\nand Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65352",previewPdfUrl:"/chapter/pdf-preview/65352",authors:[{id:"290240",title:"Dr.",name:"Marie-Jose",surname:"Mercat",slug:"marie-jose-mercat",fullName:"Marie-Jose Mercat"}],corrections:null},{id:"65338",title:"Bísaro Pig",doi:"10.5772/intechopen.83759",slug:"b-saro-pig",totalDownloads:1106,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Local pig breeds are adapted to the specific local environment and fed with various locally available feedstuffs. So besides their genetic merit for agro-biodiversity, they represent the foundations of sustainable local pork chains. Thus, the aim of the current chapter is to present the history and current status of the Bísara breed (Bísaro pig), its exterior phenotypic characteristics, geographical location, production system and main products from this Portuguese autochthonous breed of pigs. Moreover, a collection and review of available literature data, set until August 2017, on reproductive and productive traits (growth, carcass, meat and fat quality) of Bísaro pig breed were carried out. Reproductive performance has been estimated by means of sow’s age at the first parturition, annual litters per sow, piglets alive per litter, piglet live birth and weaning weight, percentage of stillborn per litter, mortality to weaning, lactation length and farrowing interval. Growth performance has been estimated through the average daily gain and feed intake in both the growing stage and the early, middle, late and overall fattening stage. Carcass traits have been evaluated by means of age and weight at slaughter, hot carcass weight, carcass yield, lean meat content, backfat thickness at withers, last rib, above the muscle gluteus medius and the loin eye area. Meat and fat quality traits of longissimus muscle have been evaluated by means of pH at 45 minutes and 24 h after slaughter, objective colour (CIE L*), intramuscular fat content and fatty acid composition of intramuscular fat. Although a considerable number of studies on Bísaro pig were included in the current review, data on meat and fat quality are scarce.",signatures:"João Santos Silva, José Pedro Araújo, Joaquim Orlando Cerqueira,\nPreciosa Pires, Carla Alves and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65338",previewPdfUrl:"/chapter/pdf-preview/65338",authors:[{id:"283731",title:"Ph.D.",name:"José Pedro",surname:"Araújo",slug:"jose-pedro-araujo",fullName:"José Pedro Araújo"},{id:"290241",title:"Dr.",name:"Joao",surname:"Santos Silva",slug:"joao-santos-silva",fullName:"Joao Santos Silva"}],corrections:null},{id:"65269",title:"Apulo-Calabrese Pig",doi:"10.5772/intechopen.83760",slug:"apulo-calabrese-pig",totalDownloads:963,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The aim of the present chapter is to present history and current status of Apulo-Calabrese pig breed, one of the local pig breeds investigated in the project TREASURE. Apulo-Calabrese breed is one of the Italian autochthonous pig breeds. Its origin dates back to the Roman times, but it suffered a drastic decline during the past century and the recovery started in the 1990s. A herd book for this breed was established in 2001, but its performances and products are practically untapped. There are 45 registered farms with around 500 breeding sows and 100 boars. Apulo-Calabrese pig is characterised by black coat colour. On average sows of Apulo-Calabrese pig breed have 1.7 litters per year with 6.9 piglets. Regarding growth performances, the potential of Apulo-Calabrese pigs in ad libitum conditions of feeding is high (≈762 g/day in middle fattening stage) although information on feed intake and feed nutritional value was scarce, which limits the evaluation of growth potential. Data on body composition, carcass traits and meat and fat quality are scarce. The present review gives a first insight into this local pig breed.",signatures:"Riccardo Bozzi, Maurizio Gallo, Claudia Geraci, Luca Fontanesi\nand Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65269",previewPdfUrl:"/chapter/pdf-preview/65269",authors:[{id:"290243",title:"Dr.",name:"Riccardo",surname:"Bozzi",slug:"riccardo-bozzi",fullName:"Riccardo Bozzi"}],corrections:null},{id:"65310",title:"Cinta Senese Pig",doi:"10.5772/intechopen.83762",slug:"cinta-senese-pig",totalDownloads:936,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cinta Senese is an Italian autochthonous pig breed, one of the local pig breeds investigated in the project TREASURE. The present chapter aims to present history and status of Cinta Senese pig breed, its phenotypic characteristics, geographical location, production system and the quality of its main products. Reproductive performance was estimated by several data: sow age at first parturition, litters/sow/year, piglets alive/litter, weaning weight, stillborn/litter, death rate percentage at weaning, duration of lactation, length of farrowing and sow age at culling. Growth performance was estimated by means of average daily gain in lactation and from birth to slaughter, growing at early, middle, late and overall fattening stage and average daily feed intake in late and overall fattening stage. Carcass traits were evaluated by means of age and weight at slaughtering, hot carcass weight, carcass yield, loin eye area and back fat thickness at the first thoracic vertebra, last rib and above gluteus medius muscle. Meat quality traits of the longissimus muscle were evaluated by means of the following: pH at 45 minutes and 24 hours after slaughtering, instrumental measurements of colour (CIE L*, a*, b*) and intramuscular fat content. Fatty acid composition was evaluated in back fat tissue.",signatures:"Carolina Pugliese, Riccardo Bozzi, Maurizio Gallo,\nClaudia Geraci, Luca Fontanesi and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65310",previewPdfUrl:"/chapter/pdf-preview/65310",authors:[{id:"290244",title:"Dr.",name:"Carolina",surname:"Pugliese",slug:"carolina-pugliese",fullName:"Carolina Pugliese"}],corrections:null},{id:"65370",title:"Black Slavonian (Crna slavonska) Pig",doi:"10.5772/intechopen.83763",slug:"black-slavonian-crna-slavonska-pig",totalDownloads:973,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Black Slavonian (Crna slavonska) pig was created during the second part of the nineteenth century using planned crossing between four pig breeds. It is an autochthonous pig breed in the Republic of Croatia and one of the local pig breeds investigated in the project TREASURE. The present chapter aims to present history and current status of Black Slavonian pig breed, its exterior phenotypic characteristics, reproductive traits, geographical location, production system and main products from this breed of pigs. Also, a collection and review of available literature data, available until August 2017, on productive traits of Black Slavonian pig breed were carried out. Growth performance was estimated utilising average daily gain and average daily feed intake in the overall fattening stage as this was the information mostly provided in considered studies. Carcass traits were evaluated by means of age and weight at slaughter, hot carcass weight, carcass yield, muscularity and back fat thickness. Meat quality traits of the longissimus muscle evaluated were objective colour and intramuscular fat content. Although a considerable number of studies on Black Slavonian pig were included in the current review, data on growth performance and some parameters of carcass, meat and fat quality are scarce.",signatures:"Vladimir Margeta, Kristina Gvozdanović, Goran Kušec, Ivona Djurkin Kušec and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65370",previewPdfUrl:"/chapter/pdf-preview/65370",authors:[{id:"290245",title:"Dr.",name:"Vladimir",surname:"Margeta",slug:"vladimir-margeta",fullName:"Vladimir Margeta"},{id:"292865",title:"Dr.",name:"Goran",surname:"Kušec",slug:"goran-kusec",fullName:"Goran Kušec"}],corrections:null},{id:"65335",title:"Gascon Pig",doi:"10.5772/intechopen.83764",slug:"gascon-pig",totalDownloads:1053,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The present chapter aims to present history and current status of Gascon pig breed, one of the local pig breeds investigated in the project TREASURE. This French autochthonous breed of pigs, which almost disappeared, now enjoys a new boom. The quality of its product is recognized by the consumers and by official quality labels (Protected Designation of Origin). Exterior phenotypic characteristics of the breed, geographical location, production system and main products are described. Reproductive performance data available in the literature and estimated from the LIGERAL database (herdbook) are presented. Literature data on production traits are also summarized for growth (early, middle, late and overall growth), feed intake, body composition and carcass traits. Meat quality traits (pH, colour, intramuscular fat content and composition) and fat tissue characteristics (fatty acid profile) are also described. Studies on Gascon pig breed are scarce and variability between studies, especially regarding productive traits, can be explained by differences in production systems, feeding regimes and feed composition according to studies. Nevertheless, the current review gives updated insights into the reproduction, production and quality traits of this local pig breed.",signatures:"Marie-José Mercat, Bénédicte Lebret, Herveline Lenoir\nand Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65335",previewPdfUrl:"/chapter/pdf-preview/65335",authors:[{id:"290240",title:"Dr.",name:"Marie-Jose",surname:"Mercat",slug:"marie-jose-mercat",fullName:"Marie-Jose Mercat"},{id:"293176",title:"Dr.",name:"Benedicte",surname:"Lebret",slug:"benedicte-lebret",fullName:"Benedicte Lebret"}],corrections:null},{id:"65300",title:"Ibérico (Iberian) Pig",doi:"10.5772/intechopen.83765",slug:"ib-rico-iberian-pig",totalDownloads:1315,totalCrossrefCites:8,totalDimensionsCites:14,hasAltmetrics:1,abstract:"The main characteristics of the Iberian breed, an autochthonous pig breed of the Iberian Peninsula, are presented in this chapter along with the results of a literature review on productive traits. Reproductive performance was estimated by sow age at first parturition, litters per sow and year, piglets alive per litter, piglet weight at birth and at weaning, percentage of stillborn per litter, mortality at weaning, lactation length and farrowing interval. For growth performance, average daily gain and daily feed intake during lactation and in different growing phases are provided. Carcass traits were evaluated by age and weight at slaughter, hot carcass weight, carcass yield, backfat thickness measurements, muscle thickness and loin eye area. Meat quality traits of longissimus muscle (pH, objective colour measurements and intramuscular fat) were also assessed. The main part of the studies considered simulated practical production conditions in Iberian pig rearing although others evaluated a defined growing period, sometimes quite far from the usual commercial slaughter weight of this breed. Therefore, some figures should be interpreted with caution. Although a considerable number of studies on Iberian pig were included in the current review, scientific papers on reproductive performance and some meat quality parameters are still rather scarce.",signatures:"Rosa Nieto, Juan García-Casco, Luis Lara, Patricia Palma-Granados,\nMercedes Izquierdo, Francisco Hernandez, Elena Dieguez,\nJuan Luis Duarte and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65300",previewPdfUrl:"/chapter/pdf-preview/65300",authors:[{id:"290236",title:"Dr.",name:"Rosa",surname:"Nieto",slug:"rosa-nieto",fullName:"Rosa Nieto"},{id:"292183",title:"Dr.",name:"Mercedes",surname:"Izquierdo",slug:"mercedes-izquierdo",fullName:"Mercedes Izquierdo"},{id:"292271",title:"Dr.",name:"Juan",surname:"García-Casco",slug:"juan-garcia-casco",fullName:"Juan García-Casco"},{id:"292278",title:"Dr.",name:"Elena",surname:"Dieguez",slug:"elena-dieguez",fullName:"Elena Dieguez"}],corrections:null},{id:"65260",title:"Krškopoljski prašič (Krškopolje Pig)",doi:"10.5772/intechopen.83767",slug:"kr-kopoljski-pra-i-kr-kopolje-pig-",totalDownloads:1086,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"This chapter presents the history and the current state-of-the-art in the only Slovenian autochthonous pig breed - Krškopolje pig. A review of literature regarding productive traits was carried out. The reproductive performance includes sow age at first parturition and at culling, litters per sow per year, number of live born and percentage of stillborn piglets per litter, piglet birth and weaning weight, mortality at weaning, duration of lactation and length of farrowing interval. Growth performance was evaluated as average daily gain in lactation, post-weaning, and early, mid, or late fattening. Daily feed intake in different stages was also assessed. Review also addresses age and weight at slaughter, and carcass traits: hot carcass weight, carcass yield, lean meat content, backfat and muscle thickness, and loin eye area. Meat quality traits considered were Longissimus muscle pH, objective colour parameters and intra muscular fat content. Additionally, fatty acid composition of intramuscular fat and backfat tissue was considered. Although studies on Krškopolje pig are scarce and the results on productive traits should be interpreted with precaution, due to different production systems and feeding strategies used in considered studies, the current review gives the first overview on this local pig breed in its current phenotype.",signatures:"Nina Batorek Lukač, Urška Tomažin, Martin Škrlep, Andrej Kastelic, Klavdija Poklukar and Marjeta Čandek-Potokar",downloadPdfUrl:"/chapter/pdf-download/65260",previewPdfUrl:"/chapter/pdf-preview/65260",authors:[{id:"23161",title:"Dr.",name:"Marjeta",surname:"Čandek-Potokar",slug:"marjeta-candek-potokar",fullName:"Marjeta Čandek-Potokar"}],corrections:null},{id:"65316",title:"Lietuvos Vietinė (Lithuanian Indigenous Wattle) Pig",doi:"10.5772/intechopen.83768",slug:"lietuvos-vietin-lithuanian-indigenous-wattle-pig",totalDownloads:913,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Lietuvos vietinė pigs were developed in Lithuanian ethnic lands following natural selection and introduction of some imported pigs. Earlier, no purposeful selection was carried out for this old Lithuanian pig breed. Lietuvos vietinė pigs as other local pig breeds are adapted to the specific local environment and could be fed with various locally available feedstuffs. So besides their genetic merit for agro-biodiversity, they represent the basis for sustainable local pork chains. The present chapter aims to present history and current status of Lietuvos vietinė pig breed, its exterior phenotypic characteristics, geographical location, production system and main products from this Lithuanian autochthonous breed of pigs, one of the local pig breeds investigated in the project TREASURE. Moreover, a collection and review of available literature data, available until August 2017, on reproductive and productive traits of Lietuvos vietinė pig breed were carried out. Reproductive and growth performance was estimated in different stages. Lean meat content was measured by ultrasonic equipment Piglog on the side of live pigs at the position of 12 ribs. Measurements of backfat thickness were taken with a ruler on the left side of carcasses at the dorsal line of the mid-back at the last rib and loin area at the 1/2 lumbar vertebra by digital camera EX-Z110 and afterwards were planimetrically measured by means of the “SCAN-STAR K” planimetrical system. Meat quality traits of the longissimus muscle were evaluated by means of pH at 45 min and 24 hours after slaughter.",signatures:"Violeta Razmaitė, Rūta Šveistienė, Virginija Jatkauskienė,\nRemigijus Juška, Raimondas Leikus and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65316",previewPdfUrl:"/chapter/pdf-preview/65316",authors:[{id:"290248",title:"Dr.",name:"Violeta",surname:"Razmaite",slug:"violeta-razmaite",fullName:"Violeta Razmaite"}],corrections:null},{id:"65280",title:"Lietuvos Baltosios Senojo Tipo (Lithuanian White) Pig",doi:"10.5772/intechopen.83771",slug:"lietuvos-baltosios-senojo-tipo-lithuanian-white-pig",totalDownloads:922,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Lietuvos Baltosios senojo tipo pigs are remaining purebred pigs of local Lithuanian pig breed (Lietuvos Baltosios) adapted to the specific local environment and locally available feedstuffs. Although previously Lietuvos Baltosios was the main dam pig breed in Lithuania, regarding scientific substantiation, their performances and products are, as in the case of Lietuvos Baltosios remains (senojo tipo-old type) pigs, practically untapped. Thus, the present chapter aims to present history and current status of Lietuvos Baltosios senojo tipo pig breed, its exterior phenotypic characteristics, geographical location, production system and main products from this Lithuanian breed of pigs, one of the local pig breeds investigated in the project TREASURE. Moreover, a collection and review of available literature data, available until August 2017, on reproductive and productive traits of Lietuvos Baltosios senojo tipo pig breed were carried out. Reproductive and growth performance, and feed intake in different stages was estimated. Lean meat content was measured by ultrasonic equipment Piglog on the side of live pigs at the position of 12 ribs. Measurements of backfat thickness were taken with a ruler on the left side of carcasses at dorsal line of the mid-back at the last rib and loin area at the 1/2 lumbar vertebra by digital camera EX-Z110 and, afterwards, were planimetrically measured by means of the “SCAN-STAR K” planimetrical system. Meat quality traits of the longissimus muscle were evaluated using pH at 45 min and 24 h after slaughter, objective colour (CIE L*, a*, b*) and intramuscular fat content.",signatures:"Violeta Razmaitė, Rūta Šveistienė, Virginija Jatkauskienė,\nRaimondas Leikus, Remigijus Juška and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65280",previewPdfUrl:"/chapter/pdf-preview/65280",authors:[{id:"290248",title:"Dr.",name:"Violeta",surname:"Razmaite",slug:"violeta-razmaite",fullName:"Violeta Razmaite"}],corrections:null},{id:"65311",title:"Mangalitsa (Swallow-Belly Mangalitsa) Pig",doi:"10.5772/intechopen.83773",slug:"mangalitsa-swallow-belly-mangalitsa-pig",totalDownloads:1134,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Autochthonous pig breed is adapted to the specific local environment, fed with various locally available feedstuffs and well adapted to extensive conditions of housing. Their genes represent safety in the production of food in future times, in which the greater importance will be attributed to the resistance and adaptability of the breed. In terms of scientific substantiation, their performances and products are, as in the case of Mangalitsa pig, practically untapped. Thus, the aim of the present chapter is to present history and current status of Mangalitsa pig breed, its exterior phenotypic characteristics, geographical distribution, production management and main products from this Serbian autochthonous breed of pigs, one of the local pig breeds investigated in the project TREASURE. Moreover, a collection and review of available literature data, available until August 2017, on reproductive and productive traits of Mangalitsa pig breed were carried out. Mangalitsa is a late and extremely fatty pig breed with low fertility, long suckling period and a very weak-slow growth. Although studies on Mangalitsa pig are scarce, the current review gives the first insight into this local pig breed.",signatures:"Čedomir Radović, Radomir Savić, Milica Petrović, Marija Gogić,\nMiloš Lukić, Dragan Radojković and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65311",previewPdfUrl:"/chapter/pdf-preview/65311",authors:[{id:"290251",title:"Dr.",name:"Cedomir",surname:"Radovic",slug:"cedomir-radovic",fullName:"Cedomir Radovic"}],corrections:null},{id:"65313",title:"Mora Romagnola Pig",doi:"10.5772/intechopen.83775",slug:"mora-romagnola-pig",totalDownloads:995,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Mora Romagnola breed, one of the Italian local pig breeds, owes its name to its colour, dark brown tending to black. Currently 31 farms are registered in the herdbook started in 2001 with about 270 breeding females and 67 boars. During the 1990s, only 18 animals were left, all concentrated in one single farm. The breed was investigated within the H2020 project TREASURE, and a collection and review of available literature data on reproductive and productive traits of Mora Romagnola pig breed were carried out. The average age of sows at first parturition was 22 months, whereas age at culling was 58 months. On average, Mora Romagnola pig breed has 8.0 piglets per parity with 1.4 parities per year. Slaughter weight was on average 163 kg with a dressing yield of 80%. Few information is available for meat quality traits. Although studies on Mora Romagnola pig are scarce, the current review gives the first insight into this local pig breed.",signatures:"Riccardo Bozzi, Maurizio Gallo, Claudia Geraci, Luca Fontanesi and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65313",previewPdfUrl:"/chapter/pdf-preview/65313",authors:[{id:"290243",title:"Dr.",name:"Riccardo",surname:"Bozzi",slug:"riccardo-bozzi",fullName:"Riccardo Bozzi"}],corrections:null},{id:"65299",title:"Moravka Pig",doi:"10.5772/intechopen.83777",slug:"moravka-pig",totalDownloads:946,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Indigenous breeds of pigs are adapted to the specific areas in which they were created. In terms of scientific substantiation, their production potential and the products obtained from them are, as in the case of Moravka pig, practically untapped. The main objective of the present chapter is to present history and current status of this breed, breeding area, its performance, production systems and main products from this local breed of pigs. Reproductive traits were estimated by means of sow age at first farrowing, litter size, weaning weight, duration of lactation and length of the farrowing interval. Growth performance was estimated by means of average daily gain and average daily feed intake in the early, middle, late and overall fattening stage. Carcass performance was evaluated by means of slaughter weight, hot carcass weight, carcass yield, lean meat content, loin eye area, the back fat thickness at the level of the last rib and withers and the back fat and muscle thickness above the gluteus medius muscle. Meat quality traits of the longissimus muscle were evaluated by means of pH at 45 min and 24 h after slaughter, objective colour (CIE L*, a* b*), intramuscular fat content and fatty acid content of intramuscular fat.",signatures:"Radomir Savić, Čedomir Radović, Milica Petrović, Marija Gogić,\nDragan Radojković and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65299",previewPdfUrl:"/chapter/pdf-preview/65299",authors:[{id:"290252",title:"Dr.",name:"Radomir",surname:"Savic",slug:"radomir-savic",fullName:"Radomir Savic"}],corrections:null},{id:"65387",title:"Negre Mallorquí (Majorcan Black) Pig",doi:"10.5772/intechopen.84434",slug:"negre-mallorqu-majorcan-black-pig",totalDownloads:968,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Negre Mallorquí pig is a native breed from Mallorca, characterized by its high rusticity and adaptation to the Mediterranean climatic conditions. The present chapter presents the history and current status of this breed, its phenotypic characteristics, the particularities of its production system and main products from this Mediterranean native pig breed. Data come from the scarce literature about Porc Negre Mallorquí breed, adding non-published data obtained during the TREASURE project. Reproductive performance was estimated by means of sow age at first parturition, litters per sow per year, piglets alive per litter, piglets birth and weaning weights, percentage of stillborn per litter, death rate percentage from birth to weaning, duration of lactation and farrowing interval. Growth performance was estimated by means of average daily gain and daily feed intake in several production periods. Carcass traits were evaluated by means of age and weight at slaughter, hot carcass weight, carcass yield and back fat thickness in several points. Meat quality traits were evaluated by means of pH at 45 min and 24 h after slaughter, objective colour, intramuscular fat content and fatty acid composition of intramuscular fat and back fat. The current chapter defines a first review about this local pig breed.",signatures:"Joan Tibau, Neus Torrentó, Raquel Quintanilla Aguado, Joel González,\nMaria Angels Oliver, Marta Gil, Jaume Jaume and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65387",previewPdfUrl:"/chapter/pdf-preview/65387",authors:[{id:"291770",title:"Dr.",name:"Joan",surname:"Tibau",slug:"joan-tibau",fullName:"Joan Tibau"},{id:"292184",title:"Dr.",name:"Joel",surname:"Gonzalez",slug:"joel-gonzalez",fullName:"Joel Gonzalez"}],corrections:null},{id:"65267",title:"Nero Casertano Pig",doi:"10.5772/intechopen.83778",slug:"nero-casertano-pig",totalDownloads:938,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The present chapter aims to present the history, current status and information of Nero Casertano pig breed investigated in the project TREASURE. As for most of the other Italian local pig breed conservation program started in 2001 and in 2015, 20 farms of Nero Casertano pigs with about 545 breeding sows and 20 boars were registered. The average age of sows at the first parturition is 16 months, whereas age at culling is 59 months. On average Nero Casertano pigs have 1.2 litters per year with 7.6 piglets. The farrowing interval (305 days on average) is prolonged compared to modern pig breeds. The fattening phase of Nero Casertano pigs is generally characterised by slower growth, and the animals were slaughtered at around 375 days of age, with an average live weight of 154 kg and a dressing yield of 81%. The breed is characterised by a high level of backfat thickness. The breed is traditionally raised with the semi-extensive system, and the most recognised trait of the Nero Casertano pig is the ‘marbling’ of the meat. This current review provides a comprehensive insight into the information for this local pig breed.",signatures:"Riccardo Bozzi, Maurizio Gallo, Claudia Geraci,\nLuca Fontanesi and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65267",previewPdfUrl:"/chapter/pdf-preview/65267",authors:[{id:"290243",title:"Dr.",name:"Riccardo",surname:"Bozzi",slug:"riccardo-bozzi",fullName:"Riccardo Bozzi"},{id:"292268",title:"Dr.",name:"Maurizio",surname:"Gallo",slug:"maurizio-gallo",fullName:"Maurizio Gallo"},{id:"292269",title:"Dr.",name:"Luca",surname:"Fontanesi",slug:"luca-fontanesi",fullName:"Luca Fontanesi"}],corrections:[{id:"66683",title:"Corrigendum to: Nero Casertano Pig",doi:null,slug:"corrigendum-to-nero-casertano-pig",totalDownloads:null,totalCrossrefCites:null,correctionPdfUrl:null}]},{id:"65298",title:"Nero Siciliano Pig",doi:"10.5772/intechopen.84438",slug:"nero-siciliano-pig",totalDownloads:997,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Origins of Nero Siciliano pig date to Carthaginian domination and its rearing, after a setback during the Arab period, was rather diffused throughout Sicily. Breed rearing is nowadays limited from the farmed area to the wooded hills of north-eastern Sicily. The latest available status (2015) reported 87 registered farms with about 1100 breeding sows and 124 boars enrolled in the herdbook started in 2001, as well as the conservation programme. Coat colour is mainly black but white face and wattles are accepted. Nero Siciliano pigs have on average 7.6 piglets of 1.4 kg live body weight and the average daily gain during fattening period was on average 346 g/day for the overall fattening stage. Slaughter age of Nero Siciliano breed was on average 390 days, at an average live weight of 95 kg. Average intramuscular fat content was 4.6% and as regards fatty acid composition, average values obtained for SFA, MUFA and PUFA were 37.5, 54.2 and 8.3% in longissimus muscle and 39.0, 49.4 and 11.7% in back fat tissue, respectively. This review gives an exhaustive review of the information available for this local Italian breed.",signatures:"Riccardo Bozzi, Maurizio Gallo, Claudia Geraci, Luca Fontanesi\nand Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65298",previewPdfUrl:"/chapter/pdf-preview/65298",authors:[{id:"290243",title:"Dr.",name:"Riccardo",surname:"Bozzi",slug:"riccardo-bozzi",fullName:"Riccardo Bozzi"}],corrections:null},{id:"65297",title:"Sarda Pig",doi:"10.5772/intechopen.84437",slug:"sarda-pig",totalDownloads:940,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Sarda pig breed (a.k.a. Suino Sardo) is a local breed from Sardinia Island (Italy) with its ancestors dating back to the Nuragic period. It is the most recent breed interested by a conservation programme among the six Italian autochthonous pig breeds investigated by the H2020 project TREASURE and could be considered untapped in terms of information on its performances and products. Thirteen farms were registered at the last census (2015) including sixty-one breeding sows and twenty boars. It is a small size breed with black, grey, tawny or spotted coat colour. On average, age at parturition is 15.7 months, with 1.6 litters per year and 7.8 piglets per parity. Average piglet mortality is rather high in the considered studies (16.1%). The average daily gain for Sarda pig within the considered studies was 423 g/day. On average, daily feed intake in the overall fattening stage was 2.3 kg/day. Sarda pigs were slaughtered at approximately 686 days of age, at an average live weight of 193 kg. Sporadic information is available for meat quality traits. Although studies on Sarda pig are scarce, the current review gives the first insight into this local pig breed.",signatures:"Riccardo Bozzi, Maurizio Gallo, Claudia Geraci, Luca Fontanesi and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65297",previewPdfUrl:"/chapter/pdf-preview/65297",authors:[{id:"290243",title:"Dr.",name:"Riccardo",surname:"Bozzi",slug:"riccardo-bozzi",fullName:"Riccardo Bozzi"}],corrections:null},{id:"65315",title:"Schwäbisch-Hällisches Pig",doi:"10.5772/intechopen.83780",slug:"schw-bisch-h-llisches-pig",totalDownloads:953,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The traditional, local breed Schwäbisch-Hällisches Schwein is originally located in the region of Hohenlohe in Baden-Württemberg, which still is the main breeding area. The breed was developed since nearly 200 years ago by the local farmers and is well adapted to the regional conditions. Next to the genetic value of the old breed in terms of biodiversity, it is the basement for a sustainable local pork chain. In terms of scientific substantiation, their performances and products are mainly untapped. Thus the aim of the present chapter is to present history and current status of Schwäbisch-Hällisches pig breed, its exterior phenotypic characteristics, geographical location, production system and main products from this German autochthonous breed of pigs, one of the local pig breeds investigated in the project TREASURE. Moreover, a collection and review of available literature data, available until August 2017, on reproductive and productive traits of Schwäbisch-Hällisches pig breed were carried out. Meat quality of longissimus muscle completed the conventional productive traits as it is of great interest in autochthonous breeds. Although studies on Schwäbisch-Hällisches pig are scarce, current review gives the first insight into this local pig breed.",signatures:"Matthias Petig, Christoph Zimmer, Rudolf Bühler and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65315",previewPdfUrl:"/chapter/pdf-preview/65315",authors:[{id:"290257",title:"Dr.",name:"Matthias",surname:"Petig",slug:"matthias-petig",fullName:"Matthias Petig"},{id:"292143",title:"Mr.",name:"Christoph",surname:"Zimmer",slug:"christoph-zimmer",fullName:"Christoph Zimmer"}],corrections:null},{id:"65288",title:"Turopolje Pig (Turopoljska svinja)",doi:"10.5772/intechopen.83782",slug:"turopolje-pig-turopoljska-svinja-",totalDownloads:925,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Turopolje pig is a fatty-type pig breed created during the Middle Ages in Turopolje region in Central Croatia. Due to its modest demands, resilience and good adaptation to outdoor rearing, the Turopolje pig has been an important food source for the local population for centuries. However, with the transition from extensive to intensive pig production in the middle of the twentieth century, this autochthonous pig breed almost disappeared. Currently, despite the state support, Turopolje pig is still endangered, with a population of only 116 sows and 14 boars. Hence, to preserve Turopolje pig breed in a more sustainable way, the breed needs to be more economically exploited and scientifically explored. Thus, the aim of this chapter is to present history and current status of Turopolje pig breed, its exterior phenotypic characteristics, geographical location, production system and main products. Moreover, a collection and review of available literature data (available until August 2017) on reproductive and productive traits, including growth performance, carcass traits and meat and fat qualities of Turopolje pig breed, were carried out. Although studies on Turopolje pig are scarce, the present review gives the first comprehensive insight into this still untapped local breed of pigs investigated in the project TREASURE.",signatures:"Danijel Karolyi, Zoran Luković, Krešimir Salajpal, Dubravko Škorput, Ivan Vnučec, Željko Mahnet, Vedran Klišanić and Nina Batorek-Lukač",downloadPdfUrl:"/chapter/pdf-download/65288",previewPdfUrl:"/chapter/pdf-preview/65288",authors:[{id:"290258",title:"Dr.",name:"Danijel",surname:"Karolyi",slug:"danijel-karolyi",fullName:"Danijel Karolyi"}],corrections:null},{id:"65224",title:"Analytical Review of Productive Performance of Local Pig Breeds",doi:"10.5772/intechopen.84214",slug:"analytical-review-of-productive-performance-of-local-pig-breeds",totalDownloads:1163,totalCrossrefCites:7,totalDimensionsCites:14,hasAltmetrics:0,abstract:"Traits of interest concerning reproductive performance, growth performance, carcass and meat quality of local pig breeds involved in H2020 project TREASURE were collected from the available literature, unpublished data available to partners or results recorded in the experiments within the project. The survey revealed great variability in the availability and quality of information. Reproductive performance of local pig breeds is lower than in conventional modern pig breeds, not only due to their genetic background but also due to the management. Data on growth rates reflect the heterogeneity of different production systems and feeding regimes used. The growth potential of the majority of local pig breeds is not well exploited, and their nutritional requirements are not known. Generally, local pig breeds show low muscular development and high potential for fat tissue deposition and are slaughtered at older age and weight, which results in higher intramuscular fat and more intense colour of meat. However, considerable differences exist between them and their potentials, not only in their production systems. For many local pig breeds studied in the project, the collected information provides the first in-depth overview of their productive performance in their preserved, present-day phenotype.",signatures:"Marjeta Čandek-Potokar, Nina Batorek Lukač, Urška Tomažin, Martin Škrlep and Rosa Nieto",downloadPdfUrl:"/chapter/pdf-download/65224",previewPdfUrl:"/chapter/pdf-preview/65224",authors:[{id:"23161",title:"Dr.",name:"Marjeta",surname:"Čandek-Potokar",slug:"marjeta-candek-potokar",fullName:"Marjeta Čandek-Potokar"}],corrections:null}],productType:{id:"3",title:"Monograph",chapterContentType:"chapter",authoredCaption:"Authored by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6384",title:"Animal Husbandry and Nutrition",subtitle:null,isOpenForSubmission:!1,hash:"45e3ab6f834a3efc7836eb8b3c8e3427",slug:"animal-husbandry-and-nutrition",bookSignature:"Banu Yücel and Turgay Taşkin",coverURL:"https://cdn.intechopen.com/books/images_new/6384.jpg",editedByType:"Edited by",editors:[{id:"191429",title:"Prof.",name:"Banu",surname:"Yucel",slug:"banu-yucel",fullName:"Banu Yucel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5987",title:"Goat Science",subtitle:null,isOpenForSubmission:!1,hash:"35f3a7d6f517410f6581d265f17ee7c9",slug:"goat-science",bookSignature:"Sándor Kukovics",coverURL:"https://cdn.intechopen.com/books/images_new/5987.jpg",editedByType:"Edited by",editors:[{id:"25894",title:"Prof.",name:"Sándor",surname:"Kukovics",slug:"sandor-kukovics",fullName:"Sándor Kukovics"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6206",title:"Ruminants",subtitle:"The Husbandry, Economic and Health Aspects",isOpenForSubmission:!1,hash:"2f4344b633afc742eb0cfc50413c928b",slug:"ruminants-the-husbandry-economic-and-health-aspects",bookSignature:"Muhammad Abubakar",coverURL:"https://cdn.intechopen.com/books/images_new/6206.jpg",editedByType:"Edited by",editors:[{id:"112070",title:"Dr.",name:"Muhammad",surname:"Abubakar",slug:"muhammad-abubakar",fullName:"Muhammad Abubakar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9081",title:"Equine Science",subtitle:null,isOpenForSubmission:!1,hash:"ac415ef2f5450fa80fdb9cf6cf32cd2d",slug:"equine-science",bookSignature:"Catrin Rutland and Albert Rizvanov",coverURL:"https://cdn.intechopen.com/books/images_new/9081.jpg",editedByType:"Edited by",editors:[{id:"202192",title:"Dr.",name:"Catrin",surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8524",title:"Lactation in Farm Animals",subtitle:"Biology, Physiological Basis, Nutritional Requirements, and Modelization",isOpenForSubmission:!1,hash:"2aa2a9a0ec13040bbf0455e34625504e",slug:"lactation-in-farm-animals-biology-physiological-basis-nutritional-requirements-and-modelization",bookSignature:"Naceur M'Hamdi",coverURL:"https://cdn.intechopen.com/books/images_new/8524.jpg",editedByType:"Edited by",editors:[{id:"73376",title:"Dr.",name:"Naceur",surname:"M'Hamdi",slug:"naceur-m'hamdi",fullName:"Naceur M'Hamdi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6993",title:"Bovine Science",subtitle:"A Key to Sustainable Development",isOpenForSubmission:!1,hash:"fe7bdc1a2e1aa960e1f51dae7c705002",slug:"bovine-science-a-key-to-sustainable-development",bookSignature:"Sadashiv S. O. and Sharangouda J. Patil",coverURL:"https://cdn.intechopen.com/books/images_new/6993.jpg",editedByType:"Edited by",editors:[{id:"176334",title:"Dr.",name:"Sadashiv",surname:"S. O.",slug:"sadashiv-s.-o.",fullName:"Sadashiv S. 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Treatment of Resistant Hypertension: An Update in Device Therapy",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/64554.pdf",downloadPdfUrl:"/chapter/pdf-download/64554",previewPdfUrl:"/chapter/pdf-preview/64554",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/64554",risUrl:"/chapter/ris/64554",chapter:{id:"59188",slug:"treatment-of-resistant-hypertension-an-update-in-device-therapy",signatures:"Ghazal Quinn, Phillip John Gary, Christopher Damiano and Geoffrey\nTeehan",dateSubmitted:"May 10th 2017",dateReviewed:"January 10th 2018",datePrePublished:"February 7th 2018",datePublished:"November 14th 2018",book:{id:"6311",title:"Blood Pressure",subtitle:"From Bench to Bed",fullTitle:"Blood Pressure - From Bench to Bed",slug:"blood-pressure-from-bench-to-bed",publishedDate:"November 14th 2018",bookSignature:"Aise Seda Artis",coverURL:"https://cdn.intechopen.com/books/images_new/6311.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"99453",title:"Dr.",name:"Aise Seda",middleName:null,surname:"Artis",slug:"aise-seda-artis",fullName:"Aise Seda Artis"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"210880",title:"Dr.",name:"Geoffrey",middleName:null,surname:"Teehan",fullName:"Geoffrey Teehan",slug:"geoffrey-teehan",email:"gteehan@comcast.net",position:null,institution:{name:"Lankenau Medical Center",institutionURL:null,country:{name:"United States of America"}}},{id:"221168",title:"Dr.",name:"Ghazal",middleName:null,surname:"Quinn",fullName:"Ghazal Quinn",slug:"ghazal-quinn",email:"quinng@mlhs.org",position:null,institution:null},{id:"221169",title:"Dr.",name:"Phillip John",middleName:null,surname:"Gary",fullName:"Phillip John Gary",slug:"phillip-john-gary",email:"garyp@mlhs.org",position:null,institution:null},{id:"221170",title:"Dr.",name:"Christopher",middleName:null,surname:"Damiano",fullName:"Christopher Damiano",slug:"christopher-damiano",email:"damianoc@mlhs.org",position:null,institution:null}]}},chapter:{id:"59188",slug:"treatment-of-resistant-hypertension-an-update-in-device-therapy",signatures:"Ghazal Quinn, Phillip John Gary, Christopher Damiano and Geoffrey\nTeehan",dateSubmitted:"May 10th 2017",dateReviewed:"January 10th 2018",datePrePublished:"February 7th 2018",datePublished:"November 14th 2018",book:{id:"6311",title:"Blood Pressure",subtitle:"From Bench to Bed",fullTitle:"Blood Pressure - From Bench to Bed",slug:"blood-pressure-from-bench-to-bed",publishedDate:"November 14th 2018",bookSignature:"Aise Seda Artis",coverURL:"https://cdn.intechopen.com/books/images_new/6311.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"99453",title:"Dr.",name:"Aise Seda",middleName:null,surname:"Artis",slug:"aise-seda-artis",fullName:"Aise Seda Artis"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"210880",title:"Dr.",name:"Geoffrey",middleName:null,surname:"Teehan",fullName:"Geoffrey Teehan",slug:"geoffrey-teehan",email:"gteehan@comcast.net",position:null,institution:{name:"Lankenau Medical Center",institutionURL:null,country:{name:"United States of America"}}},{id:"221168",title:"Dr.",name:"Ghazal",middleName:null,surname:"Quinn",fullName:"Ghazal Quinn",slug:"ghazal-quinn",email:"quinng@mlhs.org",position:null,institution:null},{id:"221169",title:"Dr.",name:"Phillip John",middleName:null,surname:"Gary",fullName:"Phillip John Gary",slug:"phillip-john-gary",email:"garyp@mlhs.org",position:null,institution:null},{id:"221170",title:"Dr.",name:"Christopher",middleName:null,surname:"Damiano",fullName:"Christopher Damiano",slug:"christopher-damiano",email:"damianoc@mlhs.org",position:null,institution:null}]},book:{id:"6311",title:"Blood Pressure",subtitle:"From Bench to Bed",fullTitle:"Blood Pressure - 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\r\n\tMycobacterium is a genus of Actinomycetota, a family of Mycobacteriaciae, with more than 190 species identified up to date. It is known to cause serious diseases in mammals and humans, most notably tuberculosis. It can be found in water, soil, and dust, and some can contaminate medications and products, including medical devices. Mycobacterium can be classified into several major groups for the purpose of diagnosis and treatment. Several species have been identified to cause a clinical threat to human beings and mammals.
\r\n
\r\n\tSome species were identified as non-pathogen and pathogens to humans and animals. If left undiagnosed and untreated may lead to major diseases that are a threat to global health—practicing healthy habits such as handwashing, cooking, and boiling water before use were observed as the best way of reducing the risk of spreading diseases caused by the pathogenic mycobacterium species. Antibiotics have been developed to treat diseases caused by this species. Most antibiotics treat the diseases well without any complications, but some can cause drug resistance if not taken properly. Adherence to medication is very important. Patients must be educated about the various diseases and medications to avoid and limit antimicrobial resistance – a major global problem.
\r\n
\r\n\tThis book will provide an up-to-date update of these developments in the pathogenicity and immunology of Mycobacteria, coupled with allied advances in diagnosis and treatment, including the use of molecular techniques, pharmacogenomics, and genomics.
",isbn:"978-1-83768-051-1",printIsbn:"978-1-83768-050-4",pdfIsbn:"978-1-83768-052-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"aa972af90c14eb4ef39b6dc71911f623",bookSignature:"Dr. Awelani Mutshembele",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11634.jpg",keywords:"Microbiologic Characteristics, Pathogenicity, Diagnosis, Transmission, Treatment, Antimicrobial Resistance, Pharmacogenomics, Drug Metabolizing Enzymes, Tuberculosis, Multidrug-Resistance, Molecular Biology Techniques, Genomics",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 12th 2022",dateEndSecondStepPublish:"July 12th 2022",dateEndThirdStepPublish:"September 10th 2022",dateEndFourthStepPublish:"November 29th 2022",dateEndFifthStepPublish:"January 28th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"8 days",secondStepPassed:!1,areRegistrationsClosed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Dr. Mutshembele is a Specialist Scientist at the Tuberculosis Platform, where she manages a portfolio of projects in Mycobacterium tuberculosis. She has a Diploma in Biotechnology from Durban University of Technology, South Africa, and was a Postdoctoral Research Fellow at the University of Pretoria. Her current research interest is the molecular epidemiology of Mycobacterium TB. She led a project on“The role of region-specific SNPs in virulence genes in Mycobacterium tuberculosis drug resistance.”",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"468847",title:"Dr.",name:"Awelani",middleName:null,surname:"Mutshembele",slug:"awelani-mutshembele",fullName:"Awelani Mutshembele",profilePictureURL:"https://mts.intechopen.com/storage/users/468847/images/system/468847.png",biography:"Dr. Mutshembele is a Specialist Scientist who joined the Tuberculosis Platform of SAMRC, South Africa as an Intramural Postdoctoral Research Fellow in 2017. 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1. Introduction
The history of medicinal herb usage dates back to the distant past, many centuries and civilizations ago. Plants have played an important role in many cultures in the treatment of various diseases, and floral fragrances have been used to refine the spirit and body, to attract partners, and to establish a psychophysical balance. The first written testimonials on the use of herbs for treatment are found in China. Emperor Kin-Nong knew about 100 medicinal plants in 3000 years BC. One of the oldest classical medical texts of ancient China is “Pent-Sao,” which was written 2500 years BC and is composed of 52 books; of which, two books are dedicated to herbal remedies. In the nineteenth century, medicinal and exotic plants have become lucrative, as more and more people began growing plants in their homes. China, Japan, and South America were overwhelmed by collectors from plant companies who looked for tropical plants to meet the needs of society. This instigated scientific pharmacy and the start of chemical and physiological research on medicinal herbs. It can be said that the nineteenth century was the century of alkaloids, because hundreds were isolated from plants from all over the world. The beginning of the twentieth century threatened medicinal herbs to be completely thrown out of use. Thus, “medicines” that have been successfully used for thousands of years have become subject to mockery and disdain. The expulsion of medicinal herbs from therapy can be compared to the darkness of the Middle Ages that had ruled Europe.
In the last four decades, especially in the developed countries of Europe and America, scientists have shown increasing interest in plant research. It is estimated that today about 60% of the total world population in treatment relies on herbs and natural products that are thus recognized as an important source of drugs [1]. Phytochemistry studies a huge variety of organic substances that have been discovered and which accumulate in plants. Furthermore, phytochemistry is also defining the structure of these compounds, their biosynthesis, metabolism, natural distribution, and biological activities [2]. An important place among them is occupied by aromatic plants, whose aroma is associated with the presence of essential oils and complex mixtures of volatile compounds, dominated by mono- and sesquiterpenes. In addition to essential oils, aromatic plants are characterized by the presence of plant phenolic compounds, primarily coumarins and phenylpropanoids, that have been shown to possess multiple pharmacological activities. Investigations of these secondary biomolecules intensified when some commercial synthetic antioxidants were found to exhibit toxic, mutagenic, and carcinogenic effects [3]. It was also found that excessive production of oxygen radicals in the body initiates the oxidation and degradation of polyunsaturated fatty acids. It is known that free radicals attack the highly unsaturated fatty acid membrane systems and induce lipid peroxidation, which is a key process in many pathological conditions and one of the reactions that cause oxidative stress. Particularly, the biological membrane lipids in the spinal cord and brain are vulnerable, because they contain high levels of polyunsaturated fatty acids. Moreover, the brain contains significant amounts of transitional prooxidant metals and consumes a lot of oxygen. These features facilitate the formation of oxygen radicals involved in the processes of aging, Alzheimer’s and Parkinson’s disease, ischemic heart damage, arthritis, myocardial infarction, arteriosclerosis, and cancer. Phenolic antioxidants “stop” free oxygen radicals and free radicals formed from the substrate by donating hydrogen atoms or electrons. Many plant species and aromatic plants have been tested because of their antioxidant and antiradical activities [4].
The aim of this chapter was to show the antioxidant role of phenolic acids and flavonoids presented in aromatic plants and to assess their potential capacity as scavengers of different free radicals.
2. Oxygen as a toxic molecule
Atmospheric oxygen (O2) is present as a biradical with two unpaired electrons, which have the same spin quantum number and are located opposite the orbited orbits. This electronic structure of molecular oxygen determines its chemical reactivity and allows the absorption of individual electrons, with the formation of numerous intermediate, partially reduced oxygen species that are commonly referred to as reactive oxygen species (ROS) [5, 6]. These reactive oxygen species are able to react with basic cellular structures and biomolecules [7] and are responsible for the emergence of many diseases and degenerative damage [8].
The normal concentration of free radicals in the body is very low. However, the effects are very disruptive, as the chain reaction allows one free radical to cause changes in thousands of molecules and damage DNA, RNA, and enzymes in cell membranes and leads to the formation of lipoxygenation products before being inactivated. Which part of the cell (proteins, nucleic acids, membrane lipids, cytosolic molecules) or the extracellular component (hyaluronic acid, collagen) will react with free radicals depends on the nature of the radical and the site of its formation (e.g., cytosolic membranes, mitochondria, endoplasmic reticulum, peroxisome, cell membranes). Due to the presence of molecular oxygen in aerobic organisms and its ability to easily receive electrons, free radicals of oxygen origin start more reactions in the cell. The reactions responsible for their formation are respiration, processes of autoxidation of hydroquinone and catecholamine, reduced transition metals, some herbicides and drugs, as well as irradiation that causes water decomposition.
2.1 The role of ROS and RNOS in the onset of many diseases
Any disorder of oxygen species’ regulation resulting from a disturbance in the balance between the formation of reactive oxygen metabolites and their elimination by the antioxidant protection system is the state of oxidative stress. In oxidative stress, the formation and accumulation of reactive metabolites are increased, resulting in oxidative processes of destruction of cellular components and genetic material.
2.1.1 Cardiovascular disease
ROS, RNOS, and LP are considered to be the major contributors to the etiology of atherosclerosis and various chronic disorders such as coronary disease, stroke, and ischemic dementia [9]. Antioxidants introduced through food can reduce the occurrence of cardiovascular diseases by inhibiting the production of free radicals and oxidative stress, protecting LDL from oxidation and aggregation, and inhibiting the synthesis of proinflammatory cytokines [10].
2.1.2 Neurodegenerative diseases
Oxidative stress often occurs in the brain, because although it represents only 2% of the body weight, the brain uses up to 20% of oxygen added. Also, the brain contains large amounts of polyunsaturated fatty acids subject to lipid peroxidation under conditions of high oxygen concentration [11, 12].
2.1.3 Carcinogenesis
Although there are insufficient facts to confirm that the presence of free radicals is necessary in the process of carcinogenesis, it is clear that they can lead to mutations, transformations, and cancers [13]. Regarding the development of cancer, the most important target for ROS is DNA. Carcinogenesis is the result of successive mutations in DNA molecules leading to uncontrolled growth and cell phenotypic modification. One of the first steps in this process is the direct interaction of electrophiles or free radicals with cellular DNA in which promutagen lesions develop. If no repair is performed, these lesions result in mutations in the next generation of cells [14]. An increased intake of antioxidants through diet or dietary supplements is associated with a reduction in the onset of cancer.
2.1.4 Aging
A reduced amount of free radicals or a reduction in the speed of their production postpones the aging process and a whole series of diseases related to the aging process [15]. A certain maximum life potential characterizes each animal species. There is a reciprocal correlation between the speed of oxygen consumption (and therefore the production of free radicals) and the maximum life potential. Some studies have shown that the aging process can be slowed by increased food intake that increases antioxidant capacity (e.g., fruit and vegetables) or by supplemental intake of vitamins E, C, and β-carotene [16].
3. Antioxidant protection systems
The process of oxidative modification of proteins, carbohydrates, DNA, and lipids is a universal mechanism of damage to the cell, especially at the membrane level. On the other hand, the numerous roles of free radicals in physiological processes make their creation a mandatory precondition of life, which is why a protective system has been established during evolutionary development. The basic role of this protection system is to reduce the amount and uncontrolled creation of free radicals and their precursors in the cell.
From a functional point of view, the antioxidant protection of the organism includes three levels of action:
Antioxidant protection systems that prevent the endogenous formation of free radicals. This level of protection is ensured by the spatial separation of processes in which free radicals are formed.
Engagement of the system in conditions of normal and enhanced formation of free radicals. According to the nature and method of action, antioxidants are divided into two types:
Enzymatic (superoxide-dismutase, catalase, xanthine oxidase, peroxidase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase). These enzymes make the so-called primary line of antioxidant protection.
Nonenzymatic or the so-called secondary line of defense.
Enzymatic antioxidants involved in the reparation of oxidative damage of lipids, proteins, carbohydrates, and nucleic acids.
3.1 Phenolic compounds
During the evolution, the plants developed effective defense mechanisms against the harmful effects of visible, ultraviolet light and radiation and are a natural source of various antioxidants. Several thousands of biologically active secondary biomolecules of higher plants for phenolic compounds (vitamin E, flavonoids, biflavonols, benzophenones, xanthones, stilbene, quinones, betacities, phenolic acids, acetophenones, phenylpropanoids, coumarins, isocoumarins, chromones, phenols, and diterpenic alcohols) and different nitrogen compounds (alkaloids, amines, amino acids, and chlorophyll derivatives) have been shown to exhibit strong antioxidant activity, but antioxidant activity of essential oils of many spice plants is intense. Their significance is higher because it has been found that many synthetic antioxidants exhibit undesired effects after a prolonged use (e.g., some of them are withdrawn from the market as a possible carcinogen). These biomolecules exhibit their activity through various mechanisms: removing free radicals, binding metal ions, inhibiting enzymatic systems that produce free radical forms, increasing the concentration of biologically important endogenous antioxidants, and inducing the expression of a variety of genes responsible for the synthesis of enzymes that inhibit oxidative stress [14]. The term “herbal phenols” encompasses a wide range of plant substances that form one of the most numerous classes of secondary biomolecules that have a common characteristic of an aromatic ring carrying one or more hydroxyl groups as substituents, including functional derivatives (esters, glycosides, etc.). However, this broad definition also includes some non-phenolic substances. For this reason, it is recommended to combine a definition that includes a chemical description and a biogenetic origin. In nature, there are two general biosynthetic pathways for the synthesis of plant phenols: (1) a polyacetate route and (2) a phenylpropanoid route with scrub acid as an intermediate. Some phenols are formed by a combination of these two times [17].
The efficiency of phenolic compounds in protection against oxidative stress depends on their reactivity in relation to toxic oxygen species and the reactivity of phenoxy radicals relative to critical biomolecules. Chemical or enzymatic oxidation of phenolic components of plant tissue results in a dark color which is of particular importance in food technology. Their susceptibility to oxidation allows their use in the protection of fats and oils.
Phenolic compounds also increase the activity of antioxidant enzymes, thus indirectly affecting the concentration of harmful oxygen radicals in the living cell. In high concentrations, radical reactions such as DNA damage, superoxide anion production, etc. can also be act as a prooxidant [18].
3.1.1 Phenolic acids
The term “phenolic acid” includes hydroxy and other functional derivatives of benzoic acid (C6▬C1) and cinnamic acid (C6▬C3) [19, 20]. Figures 1 and 2 give the structures of the basic representatives of these acids.
Figure 1.
Chemical compounds of basic benzoic acid derivatives.
Figure 2.
Chemical formulas of basic derivatives of cinnamic acid.
Cinnamic acids, especially hydroxy-cinnamic acids, have the role of basic precursors in the biosynthesis of various plant phenols. The cinnamic acid and its derivatives are produced by condensation of the acidic acids with phosphoenolpyruvate to give the horizmic acid. Additional reactions of interconversion, decarboxylation, transamination, and disinfection lead to the formation of cinnamon (3-phenylpropenoic acid) and hydroxy-cinnamic acid. Subsequent reactions of hydroxylation, methoxylation, etc. produce cimetic acid derivatives such as p-coumaric acid (p-hydroxy cinnamic acid), β-acid (2,3-dihydroxy cinnamic acid), ferulic acid (2-methoxy-3-hydroxy cinnamic acid), and synapartoic acid (2,4-dimethoxy-3-hydroxy cinnamic acid).
The derivatives of cinnamic acid, in particular hydroxy-cinnamic acids, are the basis of the overall phenylpropanoid metabolism consisting of complex biochemical reactions which as a result supply the plant with important phenolic components [21].
3.1.2 Flavonoids
The term “flavonoids” was proposed by Geisman and Heinseiner [21] to describe all plant pigments having a C6▬C3▬C6 skeleton, in which two benzene rings are linked via the C3 unit. These natural products, varying in color from white to yellow, except anthocyanidins responsible for almost all pink and violet shades [20], are widely distributed in the plant kingdom with the exception of algae and fungi. So far, more than 4000 flavonoids have been found in plants, fruits, and vegetables [22]. The most common are seeds, citrus fruits, olive oil, tea, and red wine [23]. They are found in vacuoles, chloroplasts, and chromoplasts, in the form of glycosides, and in the extinct cells free of glycosides. The presence of OH groups directly linked to the carbon atoms of the benzene ring determines the antioxidant role of flavonoids, phenolic acids, and their esters. The expressed activity is shown by compounds with two hydroxyl groups, arranged as for catechol, and three hydroxyl groups arranged as in pyrogallol.
The structure of all flavonoids is based on the C15 skeleton of the chromatic structure for which the secondary ring (B) is attached (Figure 3) [24, 25].
Figure 3.
Basic structure of flavonoids.
Flavonoids are divided according to the substitution profile of the heterocyclic ring. In the classification of flavonoids, the oxidation state of the heterocyclic ring as well as the position of the secondary aromatic ring is taken into account. A total of about 12 subgroups of flavonoids are distinguished. The secondary (B) ring may be in position 2 (flavones, flavonols, dihydroflavonols, catechins, flavans, and anthocyanidins), position 3 (isoflavonoids), or position 4 (4-phenyl-coumarins, neoflavonoids). In a few cases, the six-membered heterocyclic ring occurs in an open isomeric form (chalcones and dihydrochalcones) or is replaced by a five-membered ring.
The most widespread of all flavonoids are flavonols (3-hydroxyflavones) and flavones. The most commonly used flavonoids are quercetin, kaempferol, and myricetin. Quercetin is considered the most widespread component of all plant phenols. More than 100 glycosides of quercetin are known. Among flavonols there are about 200–300 known aglycons of these compounds [26].
3.1.3 The importance of phenolic compounds
Phenolic acids are important not only for ensuring the construction of lignin but also for regulating plant growth and disease resistance. Hydroxy-cinnamic acids are associated with the role of growth regulators and proteins in the development of certain diseases. In addition, it is possible that they are important for chloroplasts and the process of photosynthesis itself. Benzoic acid has been shown to inhibit photosynthesis in chloroplasts of spinach [17]. p-Coumaric acid is the most widespread compound among plant phenols. Furthermore, rosmarinic acid has antioxidant, anti-inflammatory, and antimicrobial effects. Its antioxidant effect is stronger than vitamin E. Rosemary acid prevents damage to cells caused by free radicals and reduces the risk of cancer and atherosclerosis. Unlike antihistamines, rosemary acid prevents the activation of immune system cells that cause swelling and fluid collection. It is used in the treatment of stomach ulcers, arthritis, cataracts, cancer, and bronchial asthma [27, 28]. Caffeic acid far exceeds other antioxidants because it reduces the production of α-toxin by more than 95%. It has been proven that high doses of coffee acids have a detrimental effect on the rats because they cause gastric papillomas. However, the combination of different antioxidants, including baconic acid, had a pronounced effect on the reduction of colon tumors in the same rats. The harmful effects of bicarbonate on human health are not known [29]. Calcium acid and its derivative caffeic acid phenethyl ester (CAPE) show a reduction in tumors and show anti-inflammatory and anticancer effects on ultraviolet-exposed skin, especially UVC and UVB rays [30]. Anticancer activity was observed in mice whose skin was treated with bee propolis and a papilloma-causing agent (TPA). CAPE significantly reduced the number of papillomas [31].
Flavonoids have a high ecological significance. They function as pigments that attract insect pollinators, not only as signal molecules for microorganisms that are useful for the plant but also as antimicrobial agents [32]. In this sense, yellow flavones and flavonols are particularly important. Because of the intense absorption of UV radiation, flavonoids protect the plant tissue from UV radiation, thereby influencing vital processes in chloroplasts.
In a pharmacological view, flavonoids show antiviral, antiallergic, antitumor, antibacterial, antifungal, and antithrombotic activity [33]. They act on blood vessels, namely, flavanones and catechins, that increase the resistance of the capillaries. They show an anti-inflammatory activity that depends on the structure of flavonoids [34]. The flavonoid anti-inflammatory activity was also confirmed by in vitro testing of the ability to inhibit lipoxygenase and cyclooxygenase [35]. Flavonoids eliminate pathological changes on capillaries and are used against diabetes, hypertension, and atherosclerosis. Flavonoids have been found to stimulate the secretion of bile and inhibit enzymes and enzymatic systems. Many flavonoids have antimicrobial and antiviral activity. A certain number of flavonoids show some cytotoxic activity. The common structural feature of cytotoxic flavonoids is trisubstituted ring A, methylation at position C4 [21].
For many flavonoids, high antioxidant activity has been demonstrated in various in vitro systems [36, 37, 38]. It has been shown that quercetin, rhamnetin, and isorhamnetin can reduce the amount of serum and liver cholesterol in addition to the in vivo antioxidant activity they show [39]. Flavonoids have been found to inhibit the activity of XOD and have the ability to capture superoxide radicals. Based on this, it is assumed that flavonoids can help in the treatment of gout and ischemia by reducing the amount of uric acid and superoxide anion of radicals in tissues [40]. Two flavonol glycoside-gallate esters showed inhibitory activity on human immunodeficiency virus-1 (HIV-1) integrase [41]. The HIV-1 integrase manages the process of incorporating viral DNA into the DNA of the host cell molecule, which is necessary for the virus to reproduce and produce virions. In this way, the inhibition of the given enzyme can be effective in anti-AIDS therapy. For example, quercetin has a beneficial effect on human health: it improves heart rate and reduces the risk of cancer. It has an anti-inflammatory and antiallergic effect. All of these effects are caused by a strong antioxidant effect of quercetin. Like many other flavonoids, quercetin inhibits the oxidation of LDL cholesterol, and its anti-inflammatory activity derives from inhibition of lipoxygenase enzyme and inhibition of inflammatory mediators. Quercetin also inhibits the release of histamine. Studies have shown that quercetin lowers the risk of prostate, uterine, breast, tissue, and colon cancer. It is presumed to reduce the production of uric acid by inhibiting XOD. It also shows NO inhibitory activity. Rutin has a strong antioxidant effect, as well as the ability to build chelates with metal ions (e.g., iron) and reduces Fenton’s reaction in which harmful oxygen radicals are produced. It is supposed to stabilize vitamin C. If rutin is taken along with vitamin C, the activity of ascorbic acid increases. Rutin strengthens the capillaries, which helps people who easily bleed or get bruises. It prevents the formation of various edemas, which is an early symptom of a chronic vein disease. It has an anti-inflammatory effect. There are indications that rutin can inhibit some carcinogenic and precancerous conditions, prevent atherogenesis, and reduce the cytotoxicity of oxidized LDL cholesterol [22]. Furthermore, kaempferol prevents arteriosclerosis by inhibiting the oxidation of low-density lipoproteins and the formation of blood platelets. It has a role of a chemopreventive agent, which means it prevents the formation of cancer cells. Quercetin has a synergistic effect in reducing the proliferation of malignant cells, so treatment with quercetin and kaempferol combinations is more effective than their individual use [42]. In addition, tangeretin acts as an anticancer agent, and in in vitro studies, it has been shown to act against some forms of malignant cells. It strengthens the cell wall and protects it from attack. It also causes apoptosis of cells suffering from leukemia, while normal cells remain undamaged [43]. Tangeretin prevents tumor suppression of intercellular bonds when transmitting the signal [44]. In the G1 phase of the cell cycle, it “freezes” the cancer cells and prevents their replication. In short, in vitro studies have shown that tangerine exhibits antimutagenic, noniinvasive, and antiproliferative activity [45]. Animal studies have shown that tangeretin reduces cholesterol levels [46] and has a potentially protective effect from Parkinson’s disease [47].
4. Lauraceae family
The Lauraceae family comprises over 2500 species, which occur within the subtropics and tropics of Eastern Asia and South and North America. Most species possess aromatic roots, stems, and fruits. One of the most well-known and most frequently used plants from this family is Laurus nobilis L., also called bay laurel. L. nobilis is a species held in high esteem since ancient times. It was dedicated to Apollo, the ancient Greek god of light, and a symbol of peace and victory used to make wreaths for emperors, generals, and poets (Figure 4) [48].
Figure 4.
Laurus nobilis L [21].
4.1 Laurus nobilis L.
Laurel is a tree or a large bush of pyramidal shape with aromatic, constantly green leaves and shiny gray corn. It reaches a height of up to 5.5 m, but the cultivated form is usually lower (1–3 m). The leaves are elliptical, fairly thick, leathery, and shiny green. Clusters of tiny, yellow, single-polar flowers appear in the spring. Berries (fruit) (Lauri Fructus), when dry, are black and wrinkled and contain two oval fat seeds. Laurel is cultivated in several cultivated forms: spp. aurea with yellowish young leaves, spp. angustifolia with narrow leaves (often called Vrbolik laurel), and spp. undulata with corrugated leaf edges. Laurel is commercially grown for aromatic leaves in Turkey, Algeria, Morocco, Portugal, Spain, Italy, France, and Mexico [49, 50].
The distillation of laurel leaves produces green-yellow volatile oil that contains a high percentage of oxidized components. Essential oil leaf (0.8–3%) contains mainly 1,8-cineol (50%) and then eugenol, acetyleugenol, methyl eugenol, α- and β-pinene, felsenren, linalool, geraniol, and terpineol. Dried berries can extract green mass (melting point about 30°C) containing several percent essential oils (0.6–10%), depending on the conditions of breeding and storage. Berries contain both volatile and fixed oils. The others are known under the common name “laurel oil” (Oleum Lauri expressum, Oleum laurinum, and Oleum Lauri unguinosum). As essential ingredients, the oil contains laurosterin, glycerol ester with lauric acid, and sesquiterpenoid (the costume and dehydrocostus lactone), while the rest is made up of fats: triglycerides with lauric, myristic, and elastic acids. As with leaves, the aroma is mainly due to terpenes (cineol, terpineol, α- and β-pinene, citral) but also cinnamic acid and its methyl ester [51].
The main flavonoids in bay leaf are quercetin, kaempferol, rutin, and their derivatives (Figure 5).
Figure 5.
Structures of the main flavonoids present in L. nobilis [21].
Kaempferol appears in the form of four nonpolar glycosides (Figure 6) [52, 53].
Figure 6.
Structures of kaempferol and its glucosides present in L. Nobilis [21].
Laurus nobilis is characterized by the presence of the other important plant phenolic substances such as phenolic acids (rosmarinic and caffeic acids) (Figure 7).
Figure 7.
Structures of two phenolic acids in L. nobilis.
As a medicinal plant, bay leaves and fruits have been employed against rheumatism, skin rashes, and earaches. In addition, it has been used as a stomachic, astringent, carminative, diaphoretic, stimulant, emetic, emmenagogue, abortifacient, and insect repellent. The essential oil is used by the cosmetic industry in creams, perfumes, and soaps.
Numerous investigations of qualitative composition of plant extracts have revealed the presence of high concentration of phenols in the extracts obtained using polar solvents [54]. The extracts that display the highest antioxidant activity have the highest concentration of phenols. Because of that, our research on laurel was recently extended to the comprehensive in vitro and in vivo studies of antioxidant activity of different extracts of leaves, to assess their potential capacity as scavengers of free radicals. Results of determination of total phenolic contents and total flavonoid contents in laurel leaf extracts are given in Table 1.
Extracts
Et2O
CHCl3
EtOAc
n-BuOH
H2O
Total phenolic content
2.41
2.85
4.53
3.96
3.20
Total flavonoid content
0.76
1.02
1.56
1.07
0.68
Table 1.
The amount of total phenolic contents (mg GAE/g d.w.) and content of total flavonoids (mg QE/g d.w.) in L. nobilis extracts.
The amount of total phenolics in L. nobilis extracts ranged from 2.41 mg GAE/g d.w. (Et2O extract) to 4.53 mg GAE/g d.w. (EtOAc extract). A significant amount of these compounds has also been observed in the n-BuOH extract (3.96 mg GAE/g d.e.). Furthermore, a considerable total flavonoid content was determined in the EtOAc and n-BuOH extracts. A little less amount of total flavonoids was determined in the CHCl3 extract, while the smallest quantity of these compounds was found in the Et2O and H2O extracts. HPLC-DAD analysis indicates a significant presence of flavonoids and phenolic in the EtOAc and n-BuOH extracts. Quercetin glycosides and flavonoids (e.g., kaempferol-3-O-Glc) were detected in EtOAc extract. In addition, the presence of phenolic acids (such as caffeic acid) and flavonoids (rutin and kaempferol) was proven in the H2O extract. The amount of flavonoids in extracts plays a significant role in their antioxidant capacity. Differences in flavonoid content between extracts and between plant organs can be explained by different numbers of secretory structures in various plant tissues [42, 55, 56].
It should be considered that the number of identified and quantified compounds in MeOH extract of L. nobilis L. has been expanded in the present work (Table 2).
Compounds
Extract
Phenolic acid
p-Hydroxybenzoic acid
38.46
Protocatechuic acid
n.d.
p-Coumaric acid
n.d.
Vanillic acid
n.d.
Gallic acid
n.d.
Caffeic acid
16.18
Quinic acid
n.d.
Ferulic acid
n.d.
Syringic acid
n.d.
Chlorogenic acid
13.11
Cinnamic acid
n.d.
Flavonoids
Apigenin
n.d.
Naringenin
n.d.
Luteolin
5.19
Kaempferol
11.97
Apigenin-7-O-β-glucoside
n.d.
Luteolin-7-O-β-glucoside
n.d.
Kaempferol-3-O-glucoside
56.15
Quercetin-3-O-glucoside
31.18
Rutin
17.44
Quercetin
21.62
Quercitrin
7.14
Table 2.
LC-MS-MS quantification of bioactive compounds presented in L. nobilis L. crude MeOH extract (μg/g d.w.).
The results indicate that the major bioactive compounds in L. nobilis extracts were kaempferol-3-O-glucoside, quercetin, and rutin. Phenolic acids were also observed in the high level, where the antioxidant, caffeic, and chlorogenic acids were found in the highest amount. Furthermore, p-hydroxybenzoic acid was also found in very high amount. The rest of the phenolic acids were not detected [57, 58, 59].
Furthermore, antioxidant activity was observed in the study of laurel leaf extracts in different solvents on the content of DPPH•, O2•−, NO•, and OH• radicals (Table 3).
Extract
Et2O
CHCl3
EtOAc
n-BuOH
H2O
DPPH radical
127.38
139.42
83.24
181.35
161.83
O2•− radical
327.60
429.43
163.57
288.64
486.32
NO radical
168.77
322.84
158.63
386.80
618.42
OH radical
442.84
241.18
121.84
213.36
187.65
Table 3.
IC50 values (μg/mL) of L. nobilis for different antioxidant assays.
The obtained results could point to strong quenching activities of flavonoids present in the leaves of laurel against DPPH radicals, and a high degree of correlation is observed between total phenol content and the ability of EtOAc extract to neutralize DPPH radicals. This is indicated by the fact that phenolic compounds play a key role in neutralizing free radical species which occurs by the mechanism of electron transfer. But, it can be supposed that such antiradical activity is also caused, besides flavonoids, by terpenoids, since nonpolar solvents also exhibited high antiradical potential. When investigating neutralization of O2•− and NO radicals, ethyl acetate extract has also exhibited the greatest ability of their scavenging. These results can be attributed to the presence of sesquiterpene lactones isolated from the plant that possess certain biological and pharmacological activity [60, 61]. Matsuda et al. [62] have also established that the methanolic extract from the leaves of L. nobilis was found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse peritoneal macrophages. It was concluded that seven sesquiterpene lactones (costunolide, dehydrocostus lactone, eremanthine, zaluzanin C, magnolialide, santamarine, and spirafolide) potently inhibited LPS-induced NO production. Inhibition of NO radicals with laurel extracts is very significant, having in mind the ability to neutralize the superoxide anion radicals as well. The common reaction between superoxide anion radical and nitrogen oxide radical yields a very reactive peroxynitrite anion (ONOO−) which is very active in reaction of nitrification of phenols—e.g., nitrification of thyroxine causes enzyme dysfunctions, and increased amounts of 3-nitrothyrozine were found in various pathological states [63]. If formation of nitroderivatives of thyroxine is prevented, the occurrence of these diseases due to oxidative stress is reduced. Ethyl acetate extract of laurel leaves is especially suited in this process since it neutralizes both superoxide anion radical and NO radical. Obtained results can be related to the experiments in which the total amount of phenols and flavonoids were determined (Table 1), which show that ethyl acetate extract of laurel leaf contains the largest amounts of total phenolic content and total flavonoid content. The cellular damage resulting from hydroxyl radical is strongest among free radicals. Hydroxyl radical can be generated by biochemical reaction. Superoxide radical is converted by superoxide dismutase (SOD) to H2O2, which can subsequently produce extremely reactive OH• radicals in the presence of transition metal ions such as iron and cooper [64, 65]. A good antioxidant potential of neutralization OH radical was shown by the EtOAc (IC50 = 121.84 μg/mL) and H2O (IC50 = 187.65 μg/mL) extracts. Such a good antioxidant activity of H2O and EtOAc extracts is expected, because it is known that the antioxidant activity of phenols is primarily a result of the ability of these compounds to act as donors of hydrogen atoms removing free radicals with the formation of less reactive phenoxyl radicals [66]. The increased stability of the formed phenoxyl radicals primarily attributed to electron delocalization and the existence of multiple resonant forms. Researching dependence of activity on the structure was found to have three structural features as important factors of radical removal potential and/or antioxidant potential of flavonoids: (1) o-dihydroxy function of ring B, which serves as the target of radicals; (2) 2,3-double bond in conjugation with 4-oxo function, which is responsible for electron delocalization of the ring B; and (3) the additional presence of 3- and 5-hydroxyl groups for the maximum radical scavenging potential [67]. The positive relationship between increased hydroxylation and increased antioxidant activity of flavonoids was found in different lipid systems, such as oil and liposome systems. Also, for phenolic acids and coumarins, it has been shown that vicinal diol groups are important for radical scavenging capacity and that methoxylation or glycosylation of o-hydroxy group in the coumarins and esterification of phenolic acids reduce the antioxidant activity of these compounds [68]. For example, it was determined that rosmarinic acid has stronger antioxidant effect than vitamin E. Rosmarinic acid prevents cell damage caused by free radicals and reduces the risk of cancer and atherosclerosis. In contrast to the histamines, rosmarinic acid prevents activation of the immune system cells that cause swelling and fluid collection [27, 69]. Furthermore, the action of some flavonoids is based on their ability to chelate transition metal ions, thereby preventing the formation of radicals (initiators of LP), catching radical initiators of LP (ROS), scavenging lipid alkoxyl and lipid peroxyl radicals, and regenerating α-tocopherol by reduction of α-tocopherol radicals. Different metals have different binding affinities of the flavonoids. Thus, for example, iron has the highest binding affinity for 3-OH group of ring C, then catechol group ring B, and at the end of 5-OH group of ring A, while the copper ions bind to the first ring catechol group B [70]. Also, in the previous investigation, on L. nobilis, different groups of chemicals were isolated (luteolin, apigenin, alkaloids, monoterpene, and germacrane alcohols) [71].
5. Conclusions
One of the paradoxes of life on Earth is that, on the one hand, oxygen is necessary for the life of aerobic organisms. On the other hand, increased concentrations of oxygen and especially its reactive metabolites (reactive oxygen species) may lead to the development of numerous diseases. A major source of free radicals in biological systems is molecular oxygen (O2). The results of our in vitro assays of examined five different extracts of Laurus nobilis leaves expressed significant protective effects on ROS (DPPH, O2•−, NO, and OH radicals), which was found to be correlated to different compounds. HPLC-DAD analysis indicates a significant presence of flavonoids and phenolic in the EtOAc and n-BuOH extracts. Quercetin glycosides and flavonoids (e.g., kaempferol-3-O-Glc) were detected in EtOAc extract. In addition, the presence of phenolic acids (such as caffeic acid) and flavonoids (rutin and kaempferol) was proven in the H2O extract. The amount of flavonoids in extracts plays a significant role in their antioxidant capacity, and it can be concluded that ethyl acetate proved to be the best solvent for extraction of plant material. Furthermore, it can be concluded that these extracts can be used in the preparation of various herbal medicines.
Acknowledgments
This work was supported by the Ministry of Science and Environmental Protection of the Republic of Serbia (Project No. 172058).
Conflict of interest
The authors declare that there is no conflict of interest.
\n',keywords:"aromatic plants, flavonoids, phenolic acids, ROS, oxidative stress",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/65331.pdf",chapterXML:"https://mts.intechopen.com/source/xml/65331.xml",downloadPdfUrl:"/chapter/pdf-download/65331",previewPdfUrl:"/chapter/pdf-preview/65331",totalDownloads:2726,totalViews:0,totalCrossrefCites:34,totalDimensionsCites:75,totalAltmetricsMentions:0,impactScore:51,impactScorePercentile:100,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"September 25th 2018",dateReviewed:"December 21st 2018",datePrePublished:"February 1st 2019",datePublished:"November 6th 2019",dateFinished:"January 24th 2019",readingETA:"0",abstract:"For centuries, aromatic herbs and spices have been added to different foods to improve the flavor and organoleptic properties. The use of aromatic plants and spices in phytotherapy is mostly related to different activities of their essential oils, such as antimicrobial, spasmolytic, carminative, hepatoprotective, antiviral, and anticarcinogenic activities. Furthermore, many studies point to strong antioxidant activities of aromatic plants and their essential oils. Knowing that phenolic compounds are the most responsible for the antioxidant activity, the amount of total phenolic contents and content of flavonoids have also been determined. In order to examine the antioxidant properties of five different extracts of Laurus nobilis L. leaves, various assays which measure free radical scavenging ability were carried out: 1,1-diphenyl-2-picrylhydrazyl, hydroxyl, superoxide anion, nitric oxide and hydroxyl radical scavenger capacity test, and lipid peroxidation assay. In all of the tests, only the EtOAc extract showed a potent antioxidant effect.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/65331",risUrl:"/chapter/ris/65331",book:{id:"8008",slug:"antioxidants"},signatures:"Biljana Kaurinovic and Djendji Vastag",authors:[{id:"142369",title:"Prof.",name:"Biljana",middleName:null,surname:"Kaurinovic",fullName:"Biljana Kaurinovic",slug:"biljana-kaurinovic",email:"biljana.kaurinovic@dh.uns.ac.rs",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"286918",title:"Prof.",name:"Djendji",middleName:null,surname:"Vastag",fullName:"Djendji Vastag",slug:"djendji-vastag",email:"djendji.vastag@dh.uns.ac.rs",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Oxygen as a toxic molecule",level:"1"},{id:"sec_2_2",title:"2.1 The role of ROS and RNOS in the onset of many diseases",level:"2"},{id:"sec_2_3",title:"2.1.1 Cardiovascular disease",level:"3"},{id:"sec_3_3",title:"2.1.2 Neurodegenerative diseases",level:"3"},{id:"sec_4_3",title:"2.1.3 Carcinogenesis",level:"3"},{id:"sec_5_3",title:"2.1.4 Aging",level:"3"},{id:"sec_8",title:"3. Antioxidant protection systems",level:"1"},{id:"sec_8_2",title:"3.1 Phenolic compounds",level:"2"},{id:"sec_8_3",title:"3.1.1 Phenolic acids",level:"3"},{id:"sec_9_3",title:"3.1.2 Flavonoids",level:"3"},{id:"sec_10_3",title:"3.1.3 The importance of phenolic compounds",level:"3"},{id:"sec_13",title:"4. Lauraceae family",level:"1"},{id:"sec_13_2",title:"4.1 Laurus nobilis L.",level:"2"},{id:"sec_15",title:"5. Conclusions",level:"1"},{id:"sec_16",title:"Acknowledgments",level:"1"},{id:"sec_19",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Harvey A. 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General Pharmacology. 1995;26:815-819'},{id:"B36",body:'Morel I, Lescoat G, Cogrel P, Sergent O, Pasdeloup N, Brissot P, et al. Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochemical Pharmacology. 1993;45:13-19'},{id:"B37",body:'Jimenez M, Garcia-Carmona F. Myricetin, an antioxidant flavonol is a substrate of polyphenol oxidase. Journal of the Science of Food and Agriculture. 1999;79:1993-2000'},{id:"B38",body:'Pekkarinen SS, Heinonen IM, Hopia IA. Flavonoids quercetin, myricetin, kaempferol and (+)-catechin as antioxidants in methyl linoleate. Journal of the Science of Food and Agriculture. 1999;79:499-506'},{id:"B39",body:'Igarashi K, Ohmuma M. Effects of isorhamnetin, rhamnetin, and quercetin on the concentrations of cholesterol and lipoperoxide in the serum and liver and on the blood and liver antioxidative enzyme activities of rats. Bioscience Biotechnology and Biochemistry. 1995;59:595-601'},{id:"B40",body:'Cos P, Ying L, Callome M, Hu JP, Cimanga K, Van Poel B, et al. Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. Journal of Natural Products. 1998;61(1):71-76'},{id:"B41",body:'Kim JH, Woo E, Shin C, Park H. A new flavonol glycoside gallate ester from acer okamotoanum and its inhibitory activity against human immunodeficiency Virus-1 (HIV1) integrase. Journal of Natural Products. 1998;61:145-148'},{id:"B42",body:'Acland ML, van de Waarsenburg S, Jones R. Synergistic antiproliferative action of the flavonols quercetin and kaempferol in cultured human cancer cell lines. In Vivo. 2005;19(1):69-76'},{id:"B43",body:'Hirano T, Abe K, Gotoh M, Oka K. Citrus flavone tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. The British Journal of Cancer. 1995;72(6):1380-1388'},{id:"B44",body:'Chaumont JP, Leger D. Campaign against allergic moulds in dwellings. inhibitor properties of essential oil geranium bourbon, citronellol, geraniol and citral. Annales Pharmaceutiques Françaises. 1992;50(3):156-166'},{id:"B45",body:'Kandaswami C, Perkins E, Soloniuk DS, Drzewiecki G, Middleton EJ. Antiproliferative effects of citrus flavonoids on a human squamous cell carcinoma in vitro. Cancer Letters. 1991;56(2):147-152'},{id:"B46",body:'Kurowska EM, Manthey JA. Hypolipidemic effects and absorption of citrus polymethoxylated flavones in hamsters with diet-induced hypercholesterolemia. Journal of Agricultural and Food Chemistry. 2004;52(10):2879-2886'},{id:"B47",body:'Datla KP, Christidou M, Widmer WW, Rooprai HK, Dexter DT. Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson’s disease. Neuroreport. 2001;12(17):3871-3875'},{id:"B48",body:'Agati A, Azzarello E, Pollastri S, Tattini M. Flavonoids as antioxidants in plants: Location and functional significance. Plant Science. 2012;96:67-76'},{id:"B49",body:'Basak SS, Candan F. Effect of Laurus nobilis L. essential oil and its main components on α-glucosidase and reactive oxygen species scavenging activity. Iranian Journal of Pharmaceutical Research. 2013;12(2):367-379'},{id:"B50",body:'Cherrat L, Espina L, Bakkali M, Garcia-Gonzalo D, Pagan R, Laglaoui A. Chemical composition and antioxidant properties of Laurus nobilis L. and Myrtus communis L. essential oils from Morocco and evaluation of their antimicrobial activity acting alone or in combined processes for food preservation. Journal of the Science of Food and Agriculture. 2014;96(6):1197-1204'},{id:"B51",body:'Fiorini C, Fouraste I, David B, Bessiere J. Composition of the flower, leaf and stem essential oils from L. nobilis L. Flavour and Fragrance Journal. 1997;12:91-93'},{id:"B52",body:'Caredda A, Marongiu B, Porcedda S, Soro C. Supercritical carbon dioxide extraction and characterization of L. nobilis essential oil. Journal of Agricultural and Food Chemistry. 2002;50:1492-1496'},{id:"B53",body:'Akgul A, Kivanc M, Bayrak A. Chemical composition and antimicrobial effect of Turkish laurel leaf oil. Journal of Essential Oil Research. 1989;1:277-280'},{id:"B54",body:'Fiorini C, David B, Fouraste I, Vercauteren J. Acylated kaempferol glycosides from Laurus nobilis leaves. Phytochemistry. 1998;47(5):821-824'},{id:"B55",body:'Škerget M, Kotnik P, Hadolin M, Rižner-Hraš A, Simonič M, Knez Ž. Phenols, proanthocyanidins, flavones and flavonols in some plant materials and their antioxidants activities. Food Chemistry. 2005;89:191-198'},{id:"B56",body:'Orčić D, Francišković M, Bekvalac K, Svirčev E, Beara I, Lesjak M, et al. Quantitative determination of plant phenolics in Urtica dioica extracts by high-performance liquid chromatography coupled with tandem mass spectrometric detection. Food Chemistry. 2014;143:48-53'},{id:"B57",body:'Čanadanović-Brunet J, Ćetković G, Djilas S, Tumbas V, Bogdanović G, Mandić A, et al. Radical scavenging, antibacterial, and antiproliferative activities of Melissa officinalis L. extracts. Journal of Medicinal Food. 2008;11:133-143'},{id:"B58",body:'Tucakov J. Healing with Herbs (Phytotherapy) (in Serbian). Beograd, Serbia: Rad; 1997. 34 p'},{id:"B59",body:'Kaurinović B, Popović M, Vlaisavljević S. In vitro and in vivo effects of Laurus nobilis L. leaf extracts. Molecules. 2010;15:3378-3390'},{id:"B60",body:'Fraga B. Natural sesquiterpenoids. Natural Product Reports. 2003;20:392-413'},{id:"B61",body:'Kaurinović B, Popović M, Ćebović T, Mimica-Dukić N. Effects of Calendula officinalis L. and Taraxacum officinale Weber (Asteraceae) extracts on the production of OH• radicals. Fresenius Environmental Bulletin. 2003;12:250-253'},{id:"B62",body:'Matsuda H, Kagerura T, Toguchida I, Ueda H, Morikawa T, Yoshikawa M. Inhibitory effects of sesquiterpene from bay leaf on nitric oxide production in lipopolysaccharide-activated macrophages: Structure requirement and role of heat shock protein induction. Life Sciences. 2000;66:2151-2157'},{id:"B63",body:'Groves JT. Peroxynitrite: Reactive, invasive, enigmatic. Current Opinion in Chemical Biology. 1999;3:226-235'},{id:"B64",body:'Hsu YC, Chan YP, Chang J. Antioxidant activity of extract from Polygonum cuspidatum. Biological Research. 2007;40:13-21'},{id:"B65",body:'Kaurinović B, Popović M, Vlaisavljević S, Schwartsowa H, Vojinović-Miloradov M. Antioxidant profile of Trifolium pratense L. Molecules. 2012;17:11156-11172'},{id:"B66",body:'Bors W, Heller W, Michel C, Saran M. Flavonoids as antioxidants: Determination of radical scavenging efficiences. Methods in Enzymology. 1990;186:343-355'},{id:"B67",body:'Pakkarinen SS, Heinonen IM, Hopia IA. Flavonoids quercetin, myricetin, kaemferol and (+)-catechin as antioxidants in methyl linoleate. Journal of the Science of Food and Agriculture. 1999;79:499-506'},{id:"B68",body:'Kaurinović B, Popović M, Vlaisavljević S, Trivić S. Antioxidant capacity of Ocimum basilicum L. and Origanum vulgare L. extracts. Molecules. 2011;16:7401-7414'},{id:"B69",body:'Cotelle N. Role of flavonoids in oxidative stress. Current Topics in Medicinal Chemistry. 2001;1:569-590'},{id:"B70",body:'Popović M, Kaurinović B, Jakovljević V, Mimica-Dukić N, Bursać M. Effect of celery (Apium graveolens) extracts on some biochemical parameters of oxidative stress in mice treated with carbon tetrachloride. Phytotherapy Research. 2006;20:531-537'},{id:"B71",body:'Vlaisavljevic S, Kaurinovic B, Popovic M, Vasiljevic S. Profile of phenolic compounds in Trifolium pratense L. extracts at different growth stages and their biological activities. International Journal of Food Properties. 2016;20(12):3090-3101'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Biljana Kaurinovic",address:"biljana.kaurinovic@dh.uns.ac.rs",affiliation:'
Department of Chemistry, Biochemistry and Environmental Protection, University of Novi Sad, Republic of Serbia
Department of Chemistry, Biochemistry and Environmental Protection, University of Novi Sad, Republic of Serbia
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1. Introduction
Triple immunosuppressive therapy including calcineurin inhibitors (CNI), anti-metabolites, and steroids, has substantially improved clinical outcomes for heart transplant (HTx) recipients. Nevertheless, the management of CNI-related nephrotoxicity, fatal acute cellular rejection (ACR), antibody-mediated rejection (AMR), and infections remains challenging [1]. Immunosuppressive regimens for organ transplantation can be generally characterized as induction, maintenance, or rescue therapies [2]. Recently, desensitization therapy has also been considered for recipients who are highly sensitized to Human leukocyte antigen (HLA) or have donor specific HLA antibodies [3]. Induction immunosuppressive therapy is a powerful and prophylactic therapy that is used perioperatively to prevent episodes of acute rejection, which is expected to improve the clinical prognosis or make their managements easier in high-risk HTx recipients. Currently, approximate 50% of HTx recipients employ a strategy of induction therapy, however, international clinical guidelines do not recommend the routine use of induction immunosuppressive therapy since the impact of induction therapy on survival in HTx recipients remains unclear [1]. In the more recent clinical situation, tacrolimus, which is recent alternative choice of cyclosporine, significantly reduces the incidence of ACR. And desensitization therapy is also becoming an established medical treatment for sensitized HTx recipients. Appropriate indications and therapeutic regimens for administering induction immunosuppressive therapy to HTx recipients requires further consideration in the recent clinical situations.
This manuscript will provide an overview of the induction immunosuppressive therapy up to now, and future perspective of the induction immunosuppressive therapy in the new era of the current more established immunosuppression.
2. Induction immunosuppressive therapy in HTx
2.1 Immune response system in transplant recipients
Immune response system that influences the rejection in transplant recipients is divided into two categories depending on the immune cells that primarily work, although each response influences the other; T-cell-mediated and antibody-mediated immune response.
2.1.1 T-cell mediated immune response
T-cell mediated immune response system in transplanted recipients is generally explained from three pathway; direct and semi-direct pathway which donor antigen presentation cell (APC) affect, and indirect pathway which recipient APC (Figure 1) [2]. Thymic selection in the native thymus occurs without regard for donor-specific allo-antigens. The naïve T cell has a relatively high allo-specific precursor frequency (Precursor frequency). This process can be nonspecifically reduced by depletion induction immunosuppressive agents including anti-thymocyte antibodies (ATG), muromonab-CD3 (OKT3), and alemtuzumab (Figure 1a). Allo-antigen is presented via donor (direct or semi-direct) or recipient-itself (indirect) APCs in the secondary lymphoid tissues inducing naïve T cell activation (Antigen presentation). In transplantation, graft derived APCs likely dominate this process early through reperfusion induced mobilization to the secondary lymphoid tissue and direct pathway. This pathway gives way to recipient derived migratory APCs later through indirect mechanisms and may also be influenced by semi-direct presentation of intact donor HLA by recipient cells. T-cell depleting agents, Interleukin 2 receptor (IL2R) blockage, and methylprednisolone limit this process (Figure 1b). T-cell activation occurs as an aggregate effect of many spectral processes (Activation threshold). Given that T cells have long been known to be important in rejection, some maintenance immunosuppressive agents including CNI, anti-metabolites and mammalian target of rapamycin (mTOR) inhibitors also alter the threshold of activation of T-cell also affect this process (Figure 1b and c). T-cells activation in the secondary lymphoid and injured endothelium and ischemic injury (Figure 1A) attenuates platelet and complement binding and activation thus activating endothelial cells and donor APCs, initiating chemotactic signals, and providing signals to lower the activation threshold of local effector cells (Figure 1B). The local cytokine milieu reinforces local cell activation and can be inhibited by IL2R-specific agents, methylprednisolone, CNIs and mTOR inhibitors (Figure 1d). Allo-sensitized memory cells and cells activated through heterologous immunity or homeostatic proliferation bypass the need for nodal presentation. Depletion agents can both attenuate and augment this effect (Figure 1e). Activated T cells and recipient APCs are attracted to the graft site by chemokines and adhesion molecule expression (Cell Trafficking). Reperfusion injury initiates donor derived APCs to mobilize toward the nodes for direct pathway. Depletion agents, polyclonal antibody and methylprednisolone limit chemotaxis and/or adhesion. Cytotoxic T lymphocyte (CTL) encounter the graft in sufficient numbers to cause clinical damage, and are reenforced by a milieu rich in T cell derived cytokines (e.g. IL-2) (Effector response). Damage to the organ occurs through contact dependent CTL activity and through the direct effect of cytolytic cytokines (e.g. TNF-α). Depletion agents and selective IL-2 receptor antibodies limits the productiveness of this response and prevents the attainment of milieu that is supportive of CTL activity (Figure 1e).
Figure 1.
T-cell mediated immune response.
2.1.2 Antibody-mediated immune response
Anti-body mediated rejection (AMR) is a major limitation to long-term HTx survival and is mainly driven by antibodies directed against the mismatched HLA Class I and Class II antigens (HLA antibodies) expressed on the allograft. Pre-sensitized patients who possess HLA antibodies are disadvantaged by having to wait longer to receive an organ from suitably matched donor. The number of pre-sensitized patients has been increasing, a trend that is likely due to the increased use of mechanical circulatory assist devices [4]. The humoral immune system is responsible for antibody production, which leads to AMR (Figure 2) [5]. Naïve B-cells are produced in the bone marrow and become activated in secondary lymphoid tissues when antigen is encountered in the presence of APC and T-helper cells. Activated B-cells develop either into plasma blast secreting low-affinity antibody or interact with follicular dendritic and T-helper cells to form germinal centers [6]. Within germinal centers, B-cells undergo proliferation, hypermutation and affinity maturation to become high-affinity antibody-secreting plasma cells or memory B-cells. Plasma cells migrate back to the bone marrow, whereas memory B-cells circulate through secondary lymphoid organs and in the peripheral circulation. Upon re-exposure to antigen, memory B-cells rapidly proliferate and differentiate into plasma cells, producing high-affinity class-switched antibodies. Sensitized patients, who have already donor-specific antibodies pre-transplantation or memory B-cells against donor HLA by previous exposure, have high risk of hyperacute humoral rejection after HTx. In addition, antibody-mediated allograft injury occurs through complement pathway activation. HLA antibody-antigen complexes on allograft endothelial cells activate C1 triggering complement cascade activation and formation of the C5b-9 membrane attack complex to cause endothelial-cell lysis and destruction. Complement products also cause injury through recruitment of inflammatory cells (C3a, C4a, C5a), mast-cell histamine release (C5a), upregulation of endothelial adhesion molecules (C5a), tissue factor synthesis and thrombotic injury (C5a, C5b-9) and Weibel-Palade bodies (WPB) exocytosis [7]. DSA also exert harmful effects independent of complement activation through Fc-receptor recruitment of inflammatory cells and release of inflammatory mediators. The resulting cellular inflammation, thrombosis, hemorrhage and lysis cause allograft injury and dysfunction.
Figure 2.
Antibody-mediated immune response.
Desensitization therapy is a specific and important option for increasing donor pool and access to transplantation for the sensitized patient, which reduces or eliminates HLA antibody and/or facilitates transplantation in the presence of DSA. Since T-B-cell interaction is also associated with the plsma-cell antibody production, T-cell directed therapy including mycophenolate acid is also considered as a desensitization therapy. ATG, an option for induction therapy, binds to cell surface antigens on T cells to injure and reduce T cells. Since humoral immune responses are suppressed when helper T cell function is reduced, ATG has the effect of decreasing sensitization by suppressing T-B cell interactions. Other agents specific to desensitization do not necessarily suppress the T dell mediated immune response. Previous consensus report suggests that post-transplant induction therapy as well as standard maintenance immunosuppression is recommended to prevent rejection in patients who have undergone desensitization [8].
2.2 Induction therapy in the current clinical situation
Historically, all organ transplantation employed induction regimens using some immunosuppressive agents [2]. Their strategies include preoperative high dose therapy with maintenance drugs, including glucocorticosteroids, antimetabolites and intravenous CNI, or specialized induction agents such as antibodies or infusion proteins. The concept that more immunosuppression is required early after transplantation is well established regarding induction therapies to prevent rejections. Specialized induction immunosuppressive agents which do not affect worsening renal function are used in the early perioperative management of patients with known or worsening renal insufficiency, as it may enable delayed initiation with calcineurin inhibitors to prevent the development of acute renal failure. Major concerns of induction therapy may be increased risk of infection and malignancy. Specialized induction immunosuppressive agents can largely be divided into two categories: depleting antibodies and non-depleting antibodies [2]. Depleting antibodies include both monoclonal (OKT3 and alemtuzumab) and polyclonal (ATG) antibodies. Depleting antibodies reduce alloreactive T cells at the time of transplantation, in turn suppressing host response to the allograft. As depleting antibodies acts primitive T-cell and also indirectly suppresses the anti-body mediated response via B-cell, resulting in a stronger suppression of immune responses more than non-depleting antibodies. While, as nondepleting antibodies inhibit T-cell activities which acts against a downstream of immune-response cascade (such as IL-2-driven cell proliferation), it may suppress rejections more specifically.
2.2.1 Current trend of Induction therapy regimens
Cai and Terasaki reviewed renal transplant recipients in the United Network for Organ Sharing (UNOS) database, [9] there had been three distinct time periods of induction regimens: (1) 1987–1993, the old, low-induction antibody era, when fewer than 30% of all kidney recipients received induction therapy, consisting mostly (80%) of anti-lymphocyte globulin or OKT3; (2) 1994–2002, the transitional, high-induction antibody era, when approximately 80% of kidney transplant recipients received induction therapy, and anti-lymphocyte globulin and OKT3 starting to be replaced by daclizumab (1998), basiliximab (1998), and rATG (1999); and (3) 2003–2010, the modern high-induction antibody era, with induction therapy remaining high, more than 80% of all transplant patients receiving induction therapy, mostly rATG, basiliximab, daclizumab, or alemtuzumab (2003). Regarding to HTx recipients, Whitson et al. evaluated the usefulness of induction therapy using UNOS database from 2001 to 2012 in HTx recipients [10]. Of the 17,857 HTx recipients, 8216 (46%) recipients had induction therapy; 55% were IL-2R antibodies (IL-2RA), 40% some depletion agents including ATG, and 4% alemtuzumab. Nozohoor et al., reviewed 27,369 adult HTx recipients in the International Society for Heart and Lung Transplantation (ISHLT) registry database, showed that 11,681 (43%) recipients had induction therapy; 59% were ATG and 41% basiliximab [11]. Tzani et al. showed the trend in induction therapy utilization in patients who underwent HTx from 1990 to 2020, using UNOS Registry Standard Analysis and Research database [12]. The utilization of induction therapy gradually increased, reaching almost 50% in 2006, and then maintained similarly until 2016, with a recent gradual decrease to almost 40 % of all HTx in 2020. The use of alemtuzumab and OKT3 decreased significantly while the use of IL-2RA and ATG increased, and since 2003, IL-2RA has been used primarily as induction therapy. The international registry data base has also showed that almost 50% of HTx programs employ a strategy of induction therapy. Although multitude induction agents are available as mentioned above, IL-2RA and polyclonal ATG were commonly used [1].
2.2.2 Current clinical implication of induction therapy
The purpose of induction therapy is primarily to achieve high intensity immunosuppression early in the postoperative period to reduce the incidence of rejection and to delay the initiation of nephrotoxic immunosuppression with CNI in recipients with compromised renal function [9]. In addition, reduced risk of incidence of rejection may result in suppressing the development of cardiac allograft vasculopathy [13]. The potential disadvantage of induction therapy is the increased risk of infection in early phase and malignancy in the long-term post-HTx [13]. A previous meta-analysis showed that acute rejection might be reduced by induction therapy compared with no induction, and did not show other clear survival benefits or harms associated with the use of any kind of T-cell antibody induction agents compared with no induction [14]. Another systematic review showed that patients receiving induction therapy had similar risk of moderate-to-severe rejection, all-cause death, infection, and cancer with patients who did not receive induction therapy [15]. A more recent retrospective analysis using large cohort date of UNOS registry showed that induction therapy was associated with lower mortality and treated rejection episodes than no induction therapy [12].
In the current clinical situation, the improvement and establishment of new maintenance immunosuppression agents such as tacrolimus replaced cyclosporine and mycophenolate mofetil replaced azathioprine have significantly reduced risk of acute T-cell mediated rejection in acute phase post-HTx, which may lead that previously observed benefits of induction therapy tend to decrease overtime. Thus, although the clinical need of induction therapy to suppress T-cell mediated rejection may be decreasing, younger patients, multiparous women, African Americans, patients with longer term ventricular assist device, [16] and patients with long ischemic time [17] may be still good indication for the induction therapy in HTx. On the other hand, long awaiting time for HTx due to the severe donor shortage and increasing in the implantation of left ventricular assist device pre-HTx have increased risk of sensitization and pre-existing renal dysfunction before HTx. Highly sensitized patients, and those with positive cross-match may also have been considered as the candidate for the induction therapy in the past, however, since evidence for desensitization therapy is being established, truly high risk patients for hyperacute antibody-mediated rejection with high intensity of donor-specific should be considered more specific desensitization rather than introduction immunosuppressive therapy. And induction therapy may be generally used in combination with desensitization therapy, not induction therapy alone [3, 5]. Patients with pre-existing renal dysfunction may still be the best indication of induction therapy in the current clinical situation [17, 18, 19, 20].
2.3 Specific agents for induction therapy
There are many specialized induction agents that are now being used to target the components of immunity heightened during transplantation. Although there is positive evidence in randomized trials and prospective studies comparing with standard maintenance regimens, no-induction or methylprednisolone induction, most trials use the surrogate endpoint of acute rejection, rather than more definitive outcome measures such as patient or graft survival. Several induction regimens have shown to measurably increase the risk of posttransplant lymphoproliferative disease (PTLD) and death from malignancy when combined with conventional maintenance immunosuppression [21]. This manuscript focuses on two specific induction immunosuppressive agents which were commonly used in current clinical situations; ATG and IL-2RA.
2.3.1 Polyclonal antibody
ATG is a polyclonal antibody derived from immunization of mainly rabbits with human thymocytes. The final product includes antibodies against multiple cell surface proteins, and HLA class 1 heavy chains, and is effective in preventing cellular immune responses against a variety of antigenic stimuli, through substantial lymphocyte depletion. Namely, ATGs bind to several antigens on T- and B-cells, causing T- and B-lymphocyte depletion. Given their broad spectrum of specificity, they have frequently been suggested to mediate their anti-rejection properties through means other than depletion, including costimulation blockade, adhesion molecule modulation, and B cell depletion. ATG is the most commonly used induction agent. Around 20% of HTx recipients receive ATG as induction therapy. There are no studies comparing ATG induction therapy with no induction therapy [15], and the efficacy of ATG induction therapy has been investigated in comparison with induction therapy with IL-2RAs which already showed the significant reduction of rejections. A large multicenter study has observed lower rates of rejection and an increased risk of infection with ATG [22].
The xenogeneic (horse or rabbit) origin of ATG may induce a host antibody response leading to acute hypersensitivity response or rarely, serum sickness on subsequent exposure, which is characterized by fevers, chills, tachycardia, hypertension or hypotension, myalgias, and rash, and may occur after the first dose. Rarely, cytokine release syndrome can occur. Furthermore, these ATGs cannot be used repeatedly for rejection to avoid a second or subsequent allergic reaction. ATG mat be left aside for future refractory rejections, not using for introduction.
2.3.2 Interleukin 2 receptor antibody
The high affinity alpha chain IL2 receptor (CD25) was the first molecule to be successfully targeted with a humanized monoclonal antibody in solid organ transplantation. IL-2RA act through the binding of the IL-2 receptor located on activated T-cells, thereby inhibiting the proliferation and differentiation of T-lymphocytes. Basiliximab is a monoclonal antibody that selectively binds to the IL-2 receptor of T-lymphocytes, blocks binding of IL-2 to the receptor complex, and inhibits IL-2 mediated T-lymphocyte proliferation [23]. Daclizumab is a humanized anti-IL-2R (CD25) monoclonal antibody that has the murine antigen-binding sequences molecularly engrafted onto a human antibody [24]; however, daclizumab has since been discontinued by the manufacturer due to diminishing use. Basiliximab is notable for a significantly lower incidence in drug-related adverse events [25], compared with other specialized agents for induction therapy. Cytokine release syndrome has not been reported after administration of this type of drug.
Three randomized trials have compared with IL-2RA vs. no induction [23, 24, 26]. A systematic review including these randomized trials showed that IL-2RAs significantly reduced the risk of acute rejection. However, because these randomized trials had a high risk of bias despite randomization, this significant superiority of the IL-2 receptor was not clear according to the random effects model. Its survival benefits were also not found [27]. Furthermore, most of the studies to date have been in HTx recipients who received cyclosporine rather than tacrolimus for primary immunosuppression, with limited evidence in the new immunosuppression era. Watanabe et al. in HTx recipients receiving tacrolimus showed that basiliximab-based induction immunosuppressive therapy might suppress mild acute cellular rejection, and improve renal function in recipients with deteriorated renal function, and resulting in the its non-inferior outcome as compared to no-induction group even in recipients with any comorbidity [17].
2.3.3 Current evidence of comparison ATG vs. IL-2 RA
Although two randomized controlled trials demonstrated that the IL-2RA, daculizmab, effectively reduced the rate of moderate and severe rejections within first year after HTx [12, 23, 24], such effect could not be observed in trials for ATG. Previous systematic review which evaluated four randomized trials comparing of ATG with IL-2RA [28, 29, 30, 31] showed that the use of IL-2RA was associated with significantly higher risk of moderate-to-severe rejection than ATG, but similar risk of death, infections, and malignancy [15]. In the retrospective analyses using large registry or cohort data in HTx, Nozohoor et al. [11] suggested that the recipients receiving ATG showed the better survival as compared with those receiving IL-2RA, however, found more malignancy post-HTx with ATG compared with basiliximab. Tzani et al. [12] showed that ATG has lower risk of treated rejection and mortality as compared with IL-2RA. And Ansari et al. in the retrospective analysis showed similar one-year survival between ATG and IL-2RA, but IL-2RA exhibited decreased long-term survival compared with ATG at 5 years and 10 years post-HTx [32]. On the other hand, Mazimba et al. [33] showed a conflict results when patients were stratified using risk of infection and rejection; IL-2RA was lower incidence of rejection but increased costs for infection in the patients with low risk of rejection and high risk of infection, and had significant lower incidence of rejection in patients with high risk of rejection and low risk infection as compared with ATG. A potential disadvantage of induction therapy is a risk of malignancies induced by its excessive immunosuppression in the long-term post-HTx [34]. ATG depletes cytotoxic T lymphocytes against organisms and virus infected cells as well as transplant organs. Therefore, ATG-based induction therapy may cytotoxic T lymphocytes against Epstein Barr virus (EBV) and EBV infected B lymphocytes which may result in primary-like EBV infection and EBV related B cell type posttransplant lymphoproliferative disorder (PTLD). Most previous studies did not show the difference of the incidence of malignancy between ATG- and IL-2RA-based induction therapies. Nozohoor et al. showed that the use of ATG may be associated with increased malignancy-related mortality, compared with no-induction [11]. Especially in pediatric HTx, ATG-based induction therapy tends to be preferred to IL-2RA-based induction therapy in younger patients, in those with congenital heart diseases, in patients requiring pre-transplant inotropic or mechanical support, and in more sensitized patients or those with longer ischemic time [35]. Children are at greatly increased risk of PTLD versus adults, and PTLD is the most common form of post-transplant malignancy in children [36]. Although the relative rarity of PTLD makes an accurate assessment of the effect of specific immunosuppressive agents difficult, a recent review concluded no increased risk of PTLD in children given ATG after pediatric HTx [35]. They speculated that it is possible that this reduction in risk may have arisen from the general trend towards less intensive maintenance therapy in recent years. ATG-based induction may also have been used to facilitate CNI-sparing or steroid sparing therapy in pediatric HTx, potentially lowering risk the risk for PTLD.
Regarding maintenance immunosuppression, tacrolimus is more potent than cyclosprone and has proven to reduce rejection rates as well as an effective rescue agent for patients with recurrent or refractory acute allograft rejection. Tacrolimus has replaced cyclosporine in many transplant centers and currently. This raises the question about effectiveness of induction therapy in current tacrolimus-based immunosuppression era. Ali et al. performed meta-analysis to explore the effect of IL-2RA vs ATG on morbidity and mortality in renal transplant patients receiving tacrolimus-based maintenance immunosuppressive therapy, which revealed no significant difference in patient and graft survival when using IL-2RA vs ATG with the tacrolimus-based maintenance immunosuppression. The difference in efficacy between ATG and basiliximab in the era of newer immunosuppressive agents needs to be explored in HTx recipients.
ATG and IL-2RA may not be compared identically as induction therapy because the pharmacological mechanisms of action, response range, and safety of the two immunosuppressive agents are very different. Induction therapy with desensitization in highly sensitized patients or patients with donor specific antibodies may be not sufficient for basiliximab, and ATG should be selected as induction therapy. On the other hand, if induction therapy is administered because of concerns about worsening renal function immediately after transplantation in non-sensitized recipients, ATG may not be appropriate because it may lead to excessive immunosuppression, and the use of safer may be appropriate. Furthermore, since xenogeneic origin of ATG, ATGs cannot be used repeatedly for rejection to avoid a second or subsequent allergic reaction, ATG may require to be left aside for future refractory rejections.
3. Future perspective regarding the induction therapy
3.1 Appropriate indication for induction therapy
The appropriate indications for administering induction therapy have not been established. Previous studies suggested that recipients with an increased risk of rejection, which were younger patients, multiparous women, African Americans, patients with longer term ventricular assist device [16], and patients with long ischemic time [17], are good indication for the induction therapy in HTx, as well as recipients with deteriorated renal function. Watanabe et al. proposed the original indication criteria which included potential difficulty in patient management including donor or recipient older age, impairment of cardiac function or pre-existing coronary atherosclerosis of donor heart in early phase after HTx which may cause intolerance to immunosuppression.
3.2 Appropriate regimens for induction therapy
There is currently no consensus regarding the dose or duration of induction agents in different types of HTx recipients, or the timing and intensity of initial CNI therapy in recipients receiving induction therapy. The immunosuppression protocols for administering induction therapy varies according to the dosage of CNI administered and applies to those recipients who require CNI withdrawal with cytolytic therapy for renal dysfunction or as a modification of the standard triple immunosuppression regimen [23, 24, 27]. And these regimens influence perioperative over- or under immunosuppression particularly, and need to be careful in patients with administered induction therapy. Minimization and optimization of baseline immunosuppressive agents may be useful for improving clinical outcomes. Regarding the optimization of maintenance immunosuppression, some landmark trials in CNI minimization and withdrawal shows the clinical usefulness, however, perioperative optimization in immunosuppression in patients with induction therapy is still controversial [23, 24, 27]. When considering the optimal immunosuppressive regimen with induction therapy, it may be useful to monitor the degree of immunosuppression. Previous review paper suggested that CD3 monitoring, or absolute lymphocyte count is useful to guide ATG dosing [35]. Where this approach is applied, the previous ISHLT guideline advise targeting a CD3 count in the range of 25–50 cells/mm3, or an absolute total lymphocyte count <100–200 cells/mm3 [37]. A previous small sample retrospective study showed the patient group managed with CD3 monitoring received a significantly lower total ATG dose, although clinical outcome including survival, rejection and infection did not differ [38]. Regarding IL-2RA based induction therapy, CD25 which expressed on activated T lymphocytes may be useful for assessing the effects of IL-2RA. A previous study monitoring the CD25 count to evaluate the effect of IL2-RA showed that a 2-dose regimen of basiliximab-based induction therapy administered on Day 0 and Day 4 after transplantation still suppressed T-lymphocyte activation for an average 40–50 days after renal transplantation [39]. Watanabe et al. performed an original regimen that CNI dosage was slowly increased to prevent further deterioration of renal dysfunction due to CNI-induced kidney injury for the recipients with renal dysfunction, and to prevent over-immunosuppression for the pretransplant sensitized recipients; trough level of tacrolimus in the induction group was significantly lower than that in the no-induction group until 3 weeks post-HTx. However, recipients receiving induction therapy showed significantly higher incidence of infectious disease. Further investigation is needed for appropriate regimens for induction therapy.
4. Conclusions
This manuscript reviews previous and more current evidence of induction therapy in HTx recipients, and discussed the appropriate therapeutic regimen and indication of induction therapy in the current clinical situation. In previous evidence, conflicting results have been reported with regard to the effect of induction therapy on long-term survival, also the comparison between ATG and IL-2RA. Appropriate patient selection and agent selection may maximize the efficacy of induction therapy. The proper use of induction therapy is still being determined. Recent advances in immunosuppressive agents have changed the clinical course of HTx recipients. Induction therapy should be selected, specifically based on their mechanism of action to specific clinical need and aim.
Acknowledgments
This work was supported by a Japan Heart Foundation Research Grant and by the JSPS KAKENHI [grant number JP19K09256] to T.W., and was supported by the JSPS KAKENHI [grant number 21H0921] to Yasunori Shintani.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"induction therapy, interleukin-2 receptor antagonists, polyclonal anti-thymocyte antibodies, acute cellular rejection, renal dysfunction",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81057.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81057.xml",downloadPdfUrl:"/chapter/pdf-download/81057",previewPdfUrl:"/chapter/pdf-preview/81057",totalDownloads:18,totalViews:0,totalCrossrefCites:0,dateSubmitted:"January 26th 2022",dateReviewed:"February 16th 2022",datePrePublished:"April 2nd 2022",datePublished:null,dateFinished:"April 2nd 2022",readingETA:"0",abstract:"The current immunosuppressive therapy including calcineurin inhibitors, mycophenolate mofetil, and steroids, has substantially suppress rejections and improved clinical outcomes in heart transplant (HTx) recipients. Nevertheless, the management of drug-related nephrotoxicity, fatal acute cellular rejection (ACR), antibody-mediated rejection and infections remains challenging. Although previous some studies suggested that perioperative induction immunosuppressive therapy may be effective for the suppressing ACR and deterioration of renal function, increased incidence of infection and malignancy was concerned in recipients with induction immunosuppressive therapy. The international society of heart and lung transplantation (ISHLT) guidelines for the care of heart transplant recipients do not recommend routine use of induction immunosuppressive therapy, except for the patients with high risk of acute rejection or renal dysfunction, however, appropriate therapeutic regimen and indication of induction immunosuppressive therapy remains unclear in HTx recipients. We review current evidence of induction immunosuppressive therapy in HTx recipients, and discuss the appropriate therapeutic regimen and indication of induction therapy.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81057",risUrl:"/chapter/ris/81057",signatures:"Takuya Watanabe, Yasumasa Tsukamoto, Hiroki Mochizuki, Masaya Shimojima, Tasuku Hada, Satsuki Fukushima, Tomoyuki Fujita and Osamu Seguchi",book:{id:"11236",type:"book",title:"Heart Transplantation - New Insights in Therapeutic Strategies",subtitle:null,fullTitle:"Heart Transplantation - New Insights in Therapeutic Strategies",slug:null,publishedDate:null,bookSignature:"Prof. Norihide Fukushima",coverURL:"https://cdn.intechopen.com/books/images_new/11236.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-433-4",printIsbn:"978-1-80355-432-7",pdfIsbn:"978-1-80355-434-1",isAvailableForWebshopOrdering:!0,editors:[{id:"284629",title:"Prof.",name:"Norihide",middleName:null,surname:"Fukushima",slug:"norihide-fukushima",fullName:"Norihide Fukushima"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Induction immunosuppressive therapy in HTx",level:"1"},{id:"sec_2_2",title:"2.1 Immune response system in transplant recipients",level:"2"},{id:"sec_2_3",title:"2.1.1 T-cell mediated immune response",level:"3"},{id:"sec_3_3",title:"2.1.2 Antibody-mediated immune response",level:"3"},{id:"sec_5_2",title:"2.2 Induction therapy in the current clinical situation",level:"2"},{id:"sec_5_3",title:"2.2.1 Current trend of Induction therapy regimens",level:"3"},{id:"sec_6_3",title:"2.2.2 Current clinical implication of induction therapy",level:"3"},{id:"sec_8_2",title:"2.3 Specific agents for induction therapy",level:"2"},{id:"sec_8_3",title:"2.3.1 Polyclonal antibody",level:"3"},{id:"sec_9_3",title:"2.3.2 Interleukin 2 receptor antibody",level:"3"},{id:"sec_10_3",title:"2.3.3 Current evidence of comparison ATG vs. IL-2 RA",level:"3"},{id:"sec_13",title:"3. Future perspective regarding the induction therapy",level:"1"},{id:"sec_13_2",title:"3.1 Appropriate indication for induction therapy",level:"2"},{id:"sec_14_2",title:"3.2 Appropriate regimens for induction therapy",level:"2"},{id:"sec_16",title:"4. Conclusions",level:"1"},{id:"sec_17",title:"Acknowledgments",level:"1"},{id:"sec_20",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Khush KK, Potena L, Cherikh WS, Chambers DC, Harhay MO, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: 37th adult heart transplantation report-2020; focus on deceased donor characteristics. The Journal of Heart and Lung Transplantation: The Official Publication of the International Society for Heart Transplantation. 2020;39:1003-1015'},{id:"B2",body:'Kirk AD. Induction immunosuppression. Transplantation. 2006;82:593-602'},{id:"B3",body:'Habal MV. Current desensitization strategies in heart transplantation. 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Induction immunosuppressive therapy in cardiac transplantation: A systematic review and meta-analysis. Heart Failure Reviews. 2018;23:641-649'},{id:"B16",body:'Higgins R, Kirklin JK, Brown RN, Rayburn BK, Wagoner L, et al. To induce or not to induce: Do patients at greatest risk for fatal rejection benefit from cytolytic induction therapy? The Journal of Heart and Lung Transplantation: The Official Publication of the International Society for Heart Transplantation. 2005;24:392-400'},{id:"B17",body:'Watanabe T, Yanase M, Seguchi O, Fujita T, Hamasaki T, et al. Influence of induction therapy using Basiliximab with delayed tacrolimus administration in heart transplant recipients—comparison with standard tacrolimus-based triple immunosuppression. Circulation Journal: Official Journal of the Japanese Circulation Society. 2020;84:2212-2223'},{id:"B18",body:'Cantarovich M, Metrakos P, Giannetti N, Cecere R, Barkun J, Tchervenkov J. 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The New England Journal of Medicine. 2005;352:2705-2713'},{id:"B25",body:'Nashan B, Moore R, Amlot P, Schmidt AG, Abeywickrama K, Soulillou JP. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group. Lancet (London, England). 1997;350:1193-1198'},{id:"B26",body:'Mehra MR, Zucker MJ, Wagoner L, Michler R, Boehmer J, et al. A multicenter, prospective, randomized, double-blind trial of basiliximab in heart transplantation. The Journal of Heart and Lung Transplantation: The Official Publication of the International Society for Heart Transplantation. 2005;24:1297-1304'},{id:"B27",body:'Moller CH, Gustafsson F, Gluud C, Steinbruchel DA. Interleukin-2 receptor antagonists as induction therapy after heart transplantation: Systematic review with meta-analysis of randomized trials. The Journal of Heart and Lung Transplantation: The Official Publication of the International Society for Heart Transplantation. 2008;27:835-842'},{id:"B28",body:'Bonaros N, Dunkler D, Kocher A, Imhof M, Grimm M, et al. Ten-year follow-up of a prospective, randomized trial of BT563/bb10 versus anti-thymocyte globulin as induction therapy after heart transplantation. The Journal of Heart and Lung Transplantation: The Official Publication of the International Society for Heart Transplantation. 2006;25:1154-1163'},{id:"B29",body:'Carrier M, Leblanc MH, Perrault LP, White M, Doyle D, et al. Basiliximab and rabbit anti-thymocyte globulin for prophylaxis of acute rejection after heart transplantation: A non-inferiority trial. The Journal of Heart and Lung Transplantation: The Official Publication of the International Society for Heart Transplantation. 2007;26:258-263'},{id:"B30",body:'Mattei MF, Redonnet M, Gandjbakhch I, Bandini AM, Billes A, et al. Lower risk of infectious deaths in cardiac transplant patients receiving basiliximab versus anti-thymocyte globulin as induction therapy. The Journal of Heart and Lung Transplantation: The Official Publication of the International Society for Heart Transplantation. 2007;26:693-699'},{id:"B31",body:'Mullen JC, Kuurstra EJ, Oreopoulos A, Bentley MJ, Wang S. A randomized controlled trial of daclizumab versus anti-thymocyte globulin induction for heart transplantation. Transplantation Research. 2014;3:14'},{id:"B32",body:'Ansari D, Lund LH, Stehlik J, Andersson B, Hoglund P, et al. Induction with anti-thymocyte globulin in heart transplantation is associated with better long-term survival compared with basiliximab. The Journal of Heart and Lung Transplantation: The Official Publication of the International Society for Heart Transplantation. 2015;34:1283-1291'},{id:"B33",body:'Mazimba S, Tallaj JA, George JF, Kirklin JK, Brown RN, Pamboukian SV. Infection and rejection risk after cardiac transplantation with induction vs. no induction: A multi-institutional study. Clinical Transplantation. 2014;28:946-952'},{id:"B34",body:'Lindenfeld J, Miller GG, Shakar SF, Zolty R, Lowes BD, et al. Drug therapy in the heart transplant recipient: Part I: Cardiac rejection and immunosuppressive drugs. Circulation. 2004;110:3734-3740'},{id:"B35",body:'Schweiger M, Zuckermann A, Beiras-Fernandez A, Berchtolld-Herz M, Boeken U, et al. A review of induction with rabbit antithymocyte globulin in pediatric heart transplant recipients. Annals of Transplantation. 2018;23:322-333'},{id:"B36",body:'Opelz G, Döhler B. Lymphomas after solid organ transplantation: A collaborative transplant study report. American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2004;4:222-230'},{id:"B37",body:'Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M, et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. The Journal of Heart and Lung Transplantation: The Official Publication of the International Society for Heart Transplantation. 2010;29:914-956'},{id:"B38",body:'Thrush PT, Gossett JG, Costello JM, Matthews KL, Nubani R, et al. Role for immune monitoring to tailor induction prophylaxis in pediatric heart recipients. Pediatric Transplantation. 2014;18:79-86'},{id:"B39",body:'Haba T, Uchida K, Katayama A, Tominaga Y, Sato T, et al. Pharmacokinetics and pharmacodynamics of a chimeric interleukin-2 receptor monoclonal antibody, basiliximab, in renal transplantation: A comparison between Japanese and non-Japanese patients. Transplantation Proceedings. 2001;33:3174-3175'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Takuya Watanabe",address:"watanabe.takuya@ncvc.go.jp",affiliation:'
Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Japan
Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Japan
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This study therefore examined land acquisition and use in Nigeria within the context of food and livelihood security. The chapter used secondary data obtained from the World Bank website, National Bureau of Statistics (NBS) and other sources. It was found that there are gender, location and income-group considerations in the allocation of land in Nigeria. While the urban land market is relatively more formal, the rural land market is informal and the transactions were not documented in most cases. The study found that bureaucratic bottlenecks, high cost of registering land and long registration procedures, and inconsistent policy regimes impede the development of land market in Nigeria. Based on the findings of the study, it was recommended that the government should reduce and make the processes to be completed in registering lands in Nigeria easier. The Land Use Act 1978 should be amended to capture the prevailing realities around customary laws and informal markets. 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Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. 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She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"355660",title:"Dr.",name:"Anitha",middleName:null,surname:"Mani",slug:"anitha-mani",fullName:"Anitha Mani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"355612",title:"Dr.",name:"Janani",middleName:null,surname:"Karthikeyan",slug:"janani-karthikeyan",fullName:"Janani Karthikeyan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334400",title:"Dr.",name:"Suvetha",middleName:null,surname:"Siva",slug:"suvetha-siva",fullName:"Suvetha Siva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}}]}},subseries:{item:{id:"20",type:"subseries",title:"Animal Nutrition",keywords:"Sustainable Animal Diets, Carbon Footprint, Meta Analyses",scope:"An essential part of animal production is nutrition. Animals need to receive a properly balanced diet. One of the new challenges we are now faced with is sustainable animal diets (STAND) that involve the 3 P’s (People, Planet, and Profitability). We must develop animal feed that does not compete with human food, use antibiotics, and explore new growth promoters options, such as plant extracts or compounds that promote feed efficiency (e.g., monensin, oils, enzymes, probiotics). These new feed options must also be environmentally friendly, reducing the Carbon footprint, CH4, N, and P emissions to the environment, with an adequate formulation of nutrients.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,series:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517"},editorialBoard:[{id:"175762",title:"Dr.",name:"Alfredo J.",middleName:null,surname:"Escribano",slug:"alfredo-j.-escribano",fullName:"Alfredo J. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. 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