Open access peer-reviewed chapter

Diseases Related to Types of Free Radicals

Written By

Narendra Maddu

Submitted: September 15th, 2018 Reviewed: December 4th, 2018 Published: March 6th, 2019

DOI: 10.5772/intechopen.82879

Chapter metrics overview

1,772 Chapter Downloads

View Full Metrics


The free radicals are reactive molecules with electron-rich groups produced during metabolic reactions occurring in the cells. These free radicals are collectively known as reactive oxygen species (ROS) and reactive nitrogen species (RNS). Lipid peroxidation products and protein carbonyls species are under the group of ROS, and nitric oxide and peroxynitrites are under the group of RNS. The malondialdehyde that reacts with LDL-C indirectly induced the risk of atherosclerosis. The protein carbonyls acts as marker of protein oxidation and exerts damage to proteins. The nitric oxide plays an important role in DNA damage, inflammation, proliferation of cancer cells, and dysfunction of apoptosis. The peroxynitrites could induce the process of lipid peroxidation, DNA damage, and may exert chronic damage to all biomolecules. The aim of the present study is that the free radicals may react with biomolecules of the cells and play an important role in the development of chronic disease conditions in the humans.


  • reactive oxygen species
  • reactive nitrogen species
  • oxidative stress
  • pathological conditions

1. Introduction

Free radical is a molecule with an unpaired electron and capable of high reactivity [1, 2]. Free radicals are found to be involved in alteration of redox system, induced DNA damage, activation of procarcinogens, these all markers of induction of cancer [3]. Some of the radicals are the superoxide (O−2), hydroxyl (OH∙), alkoxy radical (RO∙), and nitric oxide (NO), and nonradical species are hydrogen peroxide (H2O2), singlet oxygen (1O2), and peroxynitrites (ONOO▬), which play an important role in the development and progression of different pathological conditions [4]. NO-induced dose-responsive DNA strand breakage and deaminations of cytosine to uracil and 5-methylcytosine to thymine account for the mutagenicity of nitric oxide toward bacteria and mammalian cells [5]. Antioxidants are proved that reduce the actions of reactive oxygen and nitrogen species, which are capable of damaging cells and tissues [6]. The proteins contain nitrotyrosine residues accumulate in cells which disrupts multiple regulatory pathways [7].

Nitroxidative stress maker species are actively engaged in the chronic disease complications, and their toxicity is reduced by antioxidants which have protective effects [8]. The enzymes of NADPH oxidases, xanthine oxidase, uncoupled nitric oxide synthase, and mitochondria act as markers of reactive oxygen species production in all metabolic cells [9]. Free radicals thus adversely alter lipids, proteins, and DNA and trigger a number of human diseases [10]. Peroxynitrites are the leading molecule of reactive nitrogen species by enhancing the process of lipid peroxidation, DNA damage, and protein oxidation and act as molecular target for drug development for cardiovascular, inflammatory, and neurodegenerative diseases [11]. In the cells, the interaction of excess superoxides with excess nitric oxide results in the generation of peroxynitrite which specify the chronic disease conditions of stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders [12]. The reduced glutathione, glutathione disulfide, and glutathionylated proteins act as markers of redox imbalance are directly proportional to oxidative stress [13].

The ROS requires oxygen for its formation and play an important role in human health and disease [14]. The development of increased ROS production with the simultaneous dysfunction of mitochondria has been exhibited in the pathogenesis of disorders [15]. Every cell especially vascular cells are involved in the higher production of free radicals implicated in the pathogenesis of ischemic heart disease, atherosclerosis, cardiac arrhythmia, hypertension, and diabetes [16]. The scavenging role of hydrogen peroxide is performed by catalase and decreases catalase activity results in aggregation of hydrogen peroxide leads to formation of oxidative distress [17]. The aerobic metabolic reactions are faced to greater a concentration of oxygen generates and is increased oxidation it leads inflammation, mitochondrial dysfunction, and chronic kidney diseases [18]. The purpose of the present review is to investigate the role of free radicals in various physiological and pathological diseases like neuro-disorders, cancer, renal, cardiovascular, and immunological dysfunctions (Figure 1).

Figure 1.

Impact of free radicals on biomolecules present in cells leads to formation of adducts, markers of various diseases [19].


2. Oxidation and cancer

The reactive oxygen and nitrogen species (RONS) are synthesized in greater concentration by reducing antioxidant defense, and formation of redox imbalance leads to oxidative damage to the DNA and proteins in the oral squamous cell carcinoma [20]. In animals, ROS may influence cell proliferation and cell death through the activation of several signaling pathways in the development of carcinogenesis [21]. The higher level of ROS is directly proportional to the suppression of antioxidant enzymes and significant role of oxidative-induced injury in the breast cancer [22]. The prolonged exposure and intake of tobacco is strongly associated with decreased status of antioxidant enzymes, increased oxidative stress markers with the pathogenesis of oral cancer [23]. The strong correlations of ROS and RNS with lowered antioxidants are found in oral precancer and cancer [2] (Figures 23).

Figure 2.

The functions of free radicals on biomolecules and its consequences [24].

Figure 3.

Reactive oxygen species are involved in the development of various pathological disorders [38].

2.1 Free radical cause nitric oxide

The nitric oxide (NO) has dual role in health and disease and depends on its concentration. Nitric oxide is the active marker of the development of cancer by induction of angiogenesis, blood vessel formation during physiological and pathological processes [25]. NO may modulate tumor DNA repair mechanisms by upregulating p53, poly (ADP-ribose) polymerase, and DNA-dependent protein kinase (DNA-PK). The role of NO in cancer will have profound therapeutic implications for the diagnosis and treatment of disease [26]. Alterations in the NO metabolism and to increase protein nitration may contribute to the mutagenic processes and promote lung carcinogenesis [27]. NO promotes intravasation and angiogenesis to enhance cancer cell growth and increase the properties of cancer cells [28].

In lung cancer, a high level of NO is linked to chronic stages of cancer cells and protective role in the survival and proliferation of tumor cells by inhibiting apoptosis, increasing cell migration, and invasion [29]. NO and its role in carcinogenesis and tumor progression, as well as dietary chemopreventive agents have NO-modulating properties with safe cytotoxic profile [30]. The nitric oxide synthase 2-mediated production of NO/reactive nitrogen oxide species (RNS) is heavily involved in cancer progression and metastasis in different types of tumor (Figure 4) [31].

Figure 4.

The role of nitric oxide in various diseases of humans [57].

2.2 Free radical cause peroxynitrites

Peroxynitrites (ONOO▬) could able to cause DNA strand breaks and oxidize cellular thiol groups in viable rat thymocytes in a dose-dependent fashion [32]. ONOO▬ is actively involved in the disturbances of signaling pathways of epidermal growth factors indirectly induced the process of tumorigenesis [33]. The combined effects of nitric oxide and oxidized LDL forms increase the concentrations of peroxynitrites that leads to glutathionylation of p21 ras proteins which results in aberrant activation of p21 [34]. The S-nitrosylation of PTEN, Bcl2 enhanced DNA mutation, and inhibition of apoptosis results in cell proliferation and cell survival [35]. The peroxynitrite could modify the DNA and increase the DNA adducts which act as antigens is one of the factors for the autoantibody induction in cancer patients [36]. Levels of peroxynitrite and nitrosylhemoglobin can be used as highly informative markers of disease prognosis and therapeutic approach [37].

2.3 Free radical cause lipid peroxidation

Lipids are major structural components of the membranes and are highly addictable to oxidation by the presence of reactive double bonds [39]. The malondialdehyde (MDA), product of lipid peroxidation, reacts with low-density lipoproteins and indirectly induced the process of atherosclerosis [40]. The high level of oxidative stress is directly proportional to progression of tumor stages in lungs and pulmonary parenchyma [41]. The lipid peroxides are one of the ROS that enhance the DNA damage through mutations which results in decreased expression of tumor suppressor genes or increased expression of oncogenes [42]. ONOO▬ is the initiator of induction of lipid peroxidation which disrupts the membranes and lipoproteins. These ONOO▬ and MDA collectively act as cytotoxic as well as mutagenic in cancer progression [43]. The formation of oxidative stress due to imbalance of redox system in the cells through increased lipid peroxidation has been associated with human health and diseases, including cancer [44]. The lower levels of cholesterol was detected in cancer cells and suspectible to attack of free radicals enabling the penetration of RONS into the interior of the cell, inducing pro-apoptotic factors [45].


3. Neurodegenerative diseases

3.1 Free radical cause peroxynitrites

The combined effects of peroxynitrite and sulfur-containing amino acids have been implicated in Parkinson’s disease by performing the synergistic toxicity to a neuronal cell line [46]. The protein nitration in the form of nitrotyrosine residues is by the actions of peroxynitrite. Increased concentrations of both protein carbonyls and 3-nitrotyrosine have been reported in various neurodegenerative diseases like Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) [47]. The decreased activity of antioxidant enzymes with the simultaneous increase in the concentrations of peroxynitrites leads to disturbances of oxidative phosphorylation was observed in the brain mitochondria [48]. The modification of the monomers, destabilize microtubules, and major alterations in neurodegenerative diseases is performed by peroxynitrites [49]. The effects of S-nitrosylation on neuronal excitation are due to stimulation of ionotropic glutamate receptors and toxic Aβ peptides in Alzheimer’s disease [50].

3.2 Free radical cause nitric oxide

In the lower doses, nitric oxide acts as a neurotransmitter of the neuronal cells, and it exerts antimicrobial activity invading microbes in macrophages [51]. Nitric oxide played an important role in the modulation of CO2-mediated cerebral blood flow [52]. Nitric oxide is a physiological signaling molecule produced from L-arginine by enzyme of nitric oxide synthase (NOS). This enzyme occurs in three forms as neuronal (nNOS), endothelial (eNOS), and inducible nitric oxide synthase (iNOS). It increases the cGMP levels by acting as vasodilator and is involved in the neurotransmission between nervous system cells [53]. The positive association of oxidative stress and neurodegenerative conditions was observed in multiple sclerosis, stroke, and neurodegenerative disorders [54]. The ROS is actively involved in the oxidative damage to amyloid beta peptides, marker in the Alzheimer’s disease [55]. The most abundant neurotransmitter in central nervous system is glutamate which acts as the initiator of NO formation, and H2S is highly expressed in brain which is involved in the pathogenesis of various neurological disorders [56].

3.3 Free radical cause lipid peroxidation

The brain oxidative damage contributes to AD pathogenesis by the Aβ accumulation and amyloid plaque formation in the Alzheimer’s disease of Tg2576 mice [58]. The imbalance of functioning endogenous antioxidant system leads to accumulation of free radicals, which not only induces the process of lipid peroxidation but also plays a central role in neurodegeneration [59]. Lipids are critical for plasticity and function of neuronal development. The abnormalities in lipid metabolism contribute to the pathogenesis of several neurodegenerative disorders like Alzheimer’s disease and Parkinson’s disease [60]. The relationship between lipid alterations in energy metabolism and mitochondrial dysfunction in neurodegenerative disorders [61]. Deposition of abnormal aggregated proteins and disruption of metal ion homeostasis are highly associated with oxidative stress [62]. The antioxdant and free radicals of lipid peroxidation and cognition, and cognitive response to an exercise intervention program, in adults with coronary artery disease at risk of dementia [63]. The brain is more susceptible to lipid peroxidation due to its high oxygen consumption, high level of redox metal ions, reduced antioxidant defense mechanism, and high level of polyunsaturated fatty acids [64].


4. Cardiovascular diseases

4.1 Free radical cause nitric oxide

Decreased concentrations of nitric oxide may cause constriction of coronary arteries and contribute to provocation of myocardial ischemia in coronary artery disease patients. The nitric oxide present in lower amounts exerted the vascular inflammation that could lead to oxidation of lipoproteins and foam cell formation that leads to the development of the atherosclerotic plaque [65]. These ROS actively involved in atherogenesis through their formation from enzymes of xanthine oxidase, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and nitric oxide synthase [66]. The peroxynitrites directly increases sarco/endoplasmic reticulum calcium (Ca2+ ATPase) sarco/endoplasmic reticulum calcium (SERCA) activity by S-glutathiolation and irreversible oxidation of the relevant cysteine thiols in atherosclerosis [67]. An imbalance of reduced production of NO or increased production of superoxide results in the endothelial dysfunction [68].

The dual role is performed by the nitric oxide NO in the cells, and at low concentrations, it regulates normal protective functions, but at high concentration may contribute to the pathogenesis [69]. Oxidative stress, mitochondrial dysfunction, and stress-related cell death pathways (apoptosis and necrosis) are related to the improper functioning of cardiovascular system [70]. Most ROS that are generated as by-products during mitochondrial electron transport and reactive nitrogen species (RNS) are peroxynitrites and nitric oxide, contributing to the role in the development of cardiovascular disease [71]. The specific markers of ROS are altered to inflammation that enhanced the risk of atherosclerosis by diabetes [72]. The vasodilator activity of NO may be unique among therapeutic options for management of hypertension, renal disease, and left ventricular hypertrophy [73].

4.2 Free radical cause peroxynitrites

Nitric oxide is important physiological signaling molecule also known as the endothelial-derived-relaxing factor (EDRF), and can form free radicals like peroxynitrites capable of peroxidizing the LDL and proteins [74]. Formation of peroxynitrite is augmented in inflammatory-like conditions such as ischemia-reperfusion injury in the high dose manner [75]. Proinflammatory cytokines stimulate the concerted enhancement in superoxide and NO-generating activities in the heart and causes myocardial contractile failure [76]. The protein nitration and inactivation of creatine kinase during heart failure in cardiac muscles are performed by peroxynitrites [77].

Peroxynitrite depresses myocardial contractility by decreasing the ability of Ca2+ to trigger contraction through cGMP/cGMP-dependent protein kinase pathway [78]. The peroxynitrite exposure results in reduced sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a isoform) activity is a major determinant of reduced contractility in heart failure [79]. Peroxynitrites that are present in higher concentrations depicts a crucial pathogenic mechanism of stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders [12]. The synergistic performance of nitric oxide, superoxides, peroxynitrites are effect on mitochondrial function and cell death [80].

4.3 Free radical cause lipid peroxidation

Abnormalities in levels of antioxidants like GSH are associated to accumulation of lipid peroxidation in chronic heart failure [81]. Increased formation of lipid peroxides and aldehydes has been observed in atherosclerosis, ischemia-reperfusion, and heart failure [82]. Atherosclerosis, the hardening of arteries under oxidative stress is related to oxidative changes of low density lipoproteins (LDL) which is an early prediction of development of cardiovascular disease [83]. The proinflammatory effects that result from the peroxidation of lipids, which provide critical structure and function in cellular membranes, are the main sites of pollutant attack in cardiovascular diseases of atherosclerosis, arrhythmia, hypertension, and stroke [84].


5. Immunological disorders

5.1 Free radical cause nitric oxide

Peroxynitrite converts low density lipoprotein to a form recognized by the macrophage scavenger receptor and that this process is associated with modification of the protein and lipid, and with the oxidation of alpha-tocopherol to alpha-tocopherol quinine [85]. The activated macrophages are involved in the production of large amounts of nitric oxide and indirectly diminish lymphocyte proliferation [86]. Tyrosine nitration is recognized as a prevalent and significant post-translational protein modification that serves as an indicator of nitric oxide-mediated oxidative inflammatory reactions [87]. Prolonged iNOS expression peroxynitrite may exacerbate inflammatory responses mediated by NF-kappaB due to prolonged inducible nitric oxide synthase [88].

NO regulates the structural and functional activity of many immune and inflammatory cells like macrophages, T lymphocytes, antigen-presenting cells, mast cells, neutrophils, and natural killer cells [89]. The proinflammatory nature of NO is actively involved in the process of inflammation only at higher concentrations [90]. The macrophages in active state are actively engaged in the production of not only NO production but also TNFα production [91]. Stimulatory effects of NO on integrin β1 expression and Talin phosphorylation were mediated by the cGMP signaling pathway, which is likely involved in wound healing [92].

5.2 Free radical cause peroxynitrites

Physiological role for ONOO▬ as a down-modulator of immune responses and also as key mediator in cellular and tissue injury is associated with chronic activation of the immune system [93]. In chronic inflammatory diseases, peroxynitrite formed by phagocytic cells may cause damage to DNA which acts as epitopes for the production of autoantibodies [94]. The central role of peroxynitrite is performed in the control of infections in macrophages [95]. They are produced throughout the vascular system, regulate differentiation and contractility of vascular smooth muscle cells, control vascular endothelial cell proliferation and migration, mediate platelet activation and hemostasis, and significantly contribute to the immune response [96]. Elevated reactive oxygen and nitrogen species are reduced levels of glutathione with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines [97]. The ONOO▬ could be modified by the histone proteins that lead to formation of oxidatively nitrated histones in the initiation and progression of autoimmune inflammatory diseases [98]. Peroxynitrite represents both a pathophysiologically relevant endogenous cytotoxin and a cytotoxic effector against invading pathogens [99]. Being a mediator of protein oxidation and nitration, lipid peroxidation, mitochondrial dysfunction, and cell death, peroxynitrite represents both a pathophysiologically relevant endogenous cytotoxin and a cytotoxic effector against invading pathogens [99].

5.3 Free radical cause lipid peroxidation

Plasma malondialdehyde and glutathione levels have been used as a determinate of oxidative status in the chronic immunological disorders; systemic lupus erythematosus (SLE) is a complex [100]. 4-Oxo-2-nonenal (ONE) is a highly reactive aldehyde originating from the peroxidation of polyunsaturated fatty acids involved in the pathogenesis of autoimmune disorders [101]. The product of lipid peroxidation is 4-hydroxynonenal (HNE) that acts as specific marker of immunosenescence and aging-related disorders [102].


6. Renal diseases

6.1 Free radical cause peroxynitrites

Ischemia-reperfusion injury showed decreased levels of 3-nitrotyrosine-protein adducts. The iNOS-generated NO mediates damage in I-R injury possibly through ONOO▬ formation [103]. Patients with chronic renal failure (CRF) showed decreased endothelium-dependent vasodilatation to acetylcholine, have increased markers of oxidative stress, and diminished antioxidant activity [104]. ONOO▬ could induce entire mitochondrial protein nitration, responsible for the damage of renal mitochondria in diabetes [105]. Nitrosative stress is involved in cisplatin-induced nephrotoxicity in rats through peroxynitrite-induced nephrotoxicity and protein nitration [106]. Renal hypoxia and ischemia promotes the formation of reactive oxygen species (ROS) such as superoxide radical anions, peroxides, and hydroxyl radicals, that can oxidatively damage biomolecules and membranes, and affect organelle function and induce renal tubule cell injury, inflammation, and vascular dysfunction [107].

6.2 Free radical cause nitric oxide

The rate of whole body NO synthesis was increased in the end stage renal disease (ESRD) patients [108]. In several animal models of renal disease, the increase in NO synthesis is associated with reduced degree of glomerulosclerosis, infiltration of the kidney by invading macrophages [109]. The relations between endothelial and inducible nitric oxide synthases are perturbed in renal ischemia primarily as a result of endothelial dysfunction [110]. The nitric oxide is highly reactive and exerts its chronic effects only at high concentrations which are responsible for the complications of dialysis of patients with chronic kidney disease [111]. Patients with chronic kidney disease (CKD) have been found the decreased levels in all stages of CKD [112]. Intracellular nitric oxide (iNO) substantially increased the risk of renal dysfunction in patients with acute respiratory distress syndrome (ARDS) [113]. The process of oxidative stress affects kidney function by elevated the damage in renal vessels, glomeruli, and tubules [114]. In patients with multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury [115].


7. Some other type of free radicals

7.1 Hydroxyl radicals

It is the most reactive of the free radical molecules. It damages cell membranes and lipoproteins by lipid peroxidation. Damage to lipoproteins in low density lipoprotein plays an important role in atherosclerosis. ∙OH is formed by radiolysis of water and by reaction of H2O2 with ferrous (Fe2+) ions; the latter process is termed as Fenton reaction [116, 117]. The reactive oxygen species, hydroxyl (∙OH) radical is one of the potential inducers of DNA damage. A variety of adducts are formed on reaction of ∙OH radical with DNA. The ∙OH radical can attack purine and pyrimidine bases to form ∙OH radical adducts, which are both oxidizing and reducing in nature which in turn can induce base modifications and sometimes release of bases. Some of the important base modifications include 8-hydroxydeoxyguanosine (8-OHdG), 8 (or 4-,5-)-hydroxyadenine, thymine peroxide, thymine glycols, and 5-(hydroxymethyl) uracil [118].

7.2 Free radical cause lipid peroxidation

Lipids that contain phosphate groups (i.e., phospholipids) are essential components of the membranes that surround the cells and cell structures. Free radicals in the presence of oxygen may cause degradation (peroxidation) of lipids within plasma and organellar membranes. Oxidative damage is initiated when the double bonds in unsaturated fatty acids of membrane lipids are attacked by oxygen derived free radicals particularly by OH. The lipid free radical interactions yield peroxides, which are themselves unstable and reactive, and an autocatalytic chain reaction called propagation ensues which can result in extensive membrane, organellar, and cellular damage [116, 119]. Oxidative destruction of polyunsaturated fatty acids by lipid peroxidation is damaging because it may alter the integrity of cell membranes. [120].

7.3 Superoxide oxygen (O2∙—one electron)

It is generated by direct auto-oxidation of O2 during mitochondrial electron transport reaction. Alternatively, O2∙ is produced enzymatically by xanthine oxidase and cytochrome P450 in the mitochondria or cytosol [121]. O2∙ so formed is catabolized to produce H2O2 by superoxide dismutase (SOD), a metalloprotein. It is considered to be the least reactive type of ROS and the most commonly produced free radical in humans. Once it is produced, it triggers a rapid cascade of events that creates other free radicals.

7.4 Singlet oxygen

Singlet oxygen (1O2) is an electronically excited form of oxygen which is well known to be formed when photosensitizers such as chlorophyll or the aromatic dye rose Bengal absorb light energy and transfer some of that energy to molecular oxygen [122, 123]. Various nonphotosensitized mechanisms for its formation have also been reported and suggested to occur in biological systems, but the importance of such endogenous singlet oxygen formation has had a controversial history [122, 124]. Ozone (O3) is best known as occurring in the stratosphere where it shields organisms on earth from ultraviolet C and much of ultraviolet B radiations, which are the most damaging UV components of solar radiations because they are readily absorbed by DNA [125, 126]. It is also known as a respiratory system-damaging pollutant in the troposphere and ironically as a therapeutic agent in alternative medicine [127]. More recently, it was shown that antibodies or amino acids catalyze the conversion of singlet oxygen (1O2) to ozone (O3) and that this reaction occurs during the killing of bacteria by activated neutrophils [128, 129]. Since both singlet oxygen and ozone are highly reactive oxygen species, a full understanding of their mechanisms of formation and action in vivois necessary. Hence, various reported mechanisms of the endogenous formation of these reactive oxygen species (ROS), the potential relevance of such pathways in human physiology, diseases and activity of these oxidants.


8. Conclusions

The free radicals are normally synthesized during metabolic reactions in the cells and disease. These free radicals are removed by various scavenging activities of cellular and noncellular antioxidants. The imbalance of excess ROS formation and diminished activity of antioxidants results in the formation of oxidative stress which is linked with various pathological chronic conditions like cardiovascular, neurodegenerative, and renal disorders.


Conflict of interest

The authors report no declarations of interest.


  1. 1. Mukherji SM, Singh SP. Free radicals. In: Reaction Mechanism in Organic Chemistry. Madras: Macmillan India Press; 1984. p. 285
  2. 2. Choudhari SK, Chaudhary M, Gadbail AR, Sharma A, Tekade S. Oxidative and antioxidative mechanisms in oral cancer and precancer: A review. Oral Oncology. 2014;50:10-18
  3. 3. Sun Y. Free radicals, antioxidant enzymes, and carcinogenesis. Free Radical Biology & Medicine. 1990;8:583-599
  4. 4. Halliwell B. Free radicals and other reactive species in disease. In: Encyclopedia of Life Sciences. Singapore: Nature Publishing Group; 2001. pp. 1-7
  5. 5. Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR. DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proceedings of the National Academy of Sciences. 1992;89:3030-3034
  6. 6. Halliwell B. Antioxidants in human health and disease. Annual Review of Nutrition. 1996;16:33-50
  7. 7. Stadtman ER, Levine RL. Protein oxidation. Annals of the New York Academy of Sciences. 2000;899:191-208
  8. 8. Willcox JK, Ash SL, Catignani GL. Antioxidants and prevention of chronic disease. Critical Reviews in Food Science and Nutrition. 2004;44:275-295
  9. 9. Mueller CF, Laude K, McNally JS, Harrison DG. ATVB in focus: Redox mechanisms in blood vessels. Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:274-278
  10. 10. Dalle-Donne I, Scaloni A, Giustarini D, Cavarra E, Tell G, Lungarella G, et al. Proteins as biomarkers of oxidative/nitrosative stress in diseases: The contribution of redox proteomics. Mass Spectrometry Reviews. 2005;24:55-99
  11. 11. Szabo C, Ischiropoulos H, Radi R. Peroxynitrite: Biochemistry, pathophysiology and development of therapeutics. Nature Reviews. Drug Discovery. 2007;6:662-680
  12. 12. Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiological Reviews. 2007;87:315-424
  13. 13. Rossi R, Dalle-Donne I, Milzani A, Giustarini D. Oxidized forms of glutathione in peripheral blood as biomarkers of oxidative stress. Clinical Chemistry. 2006;52:1406-1414
  14. 14. Brieger K, Schiavone S, Miller FJ Jr, Krause KH. Reactive oxygen species: From health to disease. Swiss Medical Weekly. 2012;142:13659
  15. 15. Pagano G, Talamanca AA, Castello G, Cordero MD, Dischia M, Gadaleta MN, et al. Oxidative stress and mitochondrial dysfunction across broad-ranging pathologies: Toward mitochondria-targeted clinical strategies. Oxidative Medicine and Cellular Longevity. 2014;54:12-30
  16. 16. Singh R, Devi S, Gollen R. Role of free radical in atherosclerosis, diabetes and dyslipidaemia: Larger-than-life. Diabetes/Metabolism Research and Reviews. 2015;31:113-126
  17. 17. Sies H. Hydrogen peroxide as central redox signalling molecule in physiological oxidative stress: Oxidative eustress. Redox Biology. 2017;11:613-619
  18. 18. Lv W, Booz GW, Fan F, Wang Y, Roman RJ. Oxidative stress and renal fibrosis: Recent insights for the development of novel therapeutic strategies. Frontiers in Physiology. 2018;9:105
  19. 19. Acharya JD, Ghaskadbi SS. Islets and their antioxidant defense. Islets. 2010;2:225-235
  20. 20. Bahar G, Feinmesser R, Shpitzer T, Popovtzer A, Nagler RM. Salivary analysis in oral cancer patients: DNA and protein oxidation, reactive nitrogen species, and antioxidant profile. Cancer. 2007;109:54-59
  21. 21. Genestra M. Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cellular Signalling. 2007;19:1807-1819
  22. 22. Kasapovic J, Pejic S, Todorovic A, Stojiljkovic V, Pajovic SB. Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages. Cell Biochemistry and Function. 2008;26:723-730
  23. 23. Patel BP, Rawal UM, Rawal RM, Shukla SN, Patel PS. Tobacco, antioxidant enzymes, oxidative stress, and genetic susceptibility in oral caner. American Journal of Clinical Oncology. 2008;31:454-459
  24. 24. Zhao J, Wang S, Zhong W, Yang B, Sun L, Zheng Y. Oxidative stress in the trabecular meshwork (Review). International Journal of Molecular Medicine. 2016;38:995-1002
  25. 25. Ziche M, Morbidelli L. Nitric oxide and angiogenesis. Journal of Neuro-Oncology. 2000;50:139-148
  26. 26. Xu W, Liu LZ, Loizidou M, Ahmed M, Charles IG. The role of nitric oxide in cancer. Cell Research. 2002;12:311-320
  27. 27. Masri FA, Comhair SA, Koeck T, Xu W, Janocha A, Ghosh S, et al. Abnormalities in nitric oxide and its derivatives in lung cancer. American Journal of Respiratory and Critical Care Medicine. 2005;172:597-605
  28. 28. Cheng H, Wang L, Mollica M, Re AT, Wu S, Zuo L. Nitric oxide in cancer metastasis. Cancer Letters. 2014;353:1-7
  29. 29. Luanpitpong S, Chanvorachote P. Nitric oxide and aggressive behavior of lung cancer cells. Anticancer Research. 2015;35:4585-4592
  30. 30. Vahora H, Khan MA, Alalami U, Hussain A. The potential role of nitric oxide in halting cancer progression through chemoprevention. Journal of Cancer Prevention. 2016;21:1-12
  31. 31. Somasundaram V, Basudhar D, Bharadwaj G, No JH, Ridnour LA, Cheng RYS, et al. Molecular mechanisms of nitric oxide in cancer progression, signal transduction, and metabolism. Antioxidants & Redox Signaling. 2018. DOI: 10.1089/ars.2018.7527
  32. 32. Salgo MG, Bermúdez E, Squadrito GL, Pryor WA. Peroxynitrite causes DNA damage and oxidation of thiols in rat thymocytes. Archives of Biochemistry and Biophysics. 1995;322:500-505
  33. 33. Vander Vliet A, Hristova M, Cross CE, Eiserich JP, Goldkorn T. Peroxynitrite induces covalent dimerization of epidermal growth factor receptors in A 431 epidermoid carcinoma cells. The Journal of Biological Chemistry. 1998;273:31860-31866
  34. 34. Clavreul N, Adachi T, Pimental DR, Ido Y, Schoneich C, Cohen RA. S-glutathiolation by peroxynitrite of p21ras at cysteine 118 mediates its direct activation and downstream signaling in endothelial cells. The FASEB Journal. 2006;20:518-520
  35. 35. Floyd RA, Kotake Y, Towner RA, Xing GW, Nakae D, Konishi Y. Nitric oxide and cancer development. Journal of Toxicologic Pathology. 2007;20:77-92
  36. 36. Habib S, Moinuddin Ali A, Ali R. Preferential recognition of peroxynitrite modified human DNA by circulating autoantibodies in cancer patients. Cellular Immunology. 2009;254:117-123
  37. 37. Guskova E, Ivanovich Kit O, Guskova N, Goroshinskaya IA, Nerodo GA, Chernikova NV. Predictors of prognosis and assessment of effectiveness of treatment for recurrent cervical cancer. Journal of Clinical Oncology. 2017;34:e17024
  38. 38. Valko M, Jomova K, Rhodes CJ, Kuca K, Musilek K. Redox- and non-redox-metal-induced formation of free radicals and their role in human disease. Archives of Toxicology. 2016;90:1-37
  39. 39. Porter NA, Caldwell SE, Mills KA. Mechanisms of free radical oxidation of unsaturated lipids. Lipids. 1995;30:277-290
  40. 40. Slatter DA, Bolton CH, Bailey AJ. The importance of lipid-derived malondialdehyde in diabetes mellitus. Diabetologia. 2000;43:550-557
  41. 41. Zieba M, Suwalski M, Kwiatkowska S, Piasecka G, Grzelewska-Rzymowska I, Stolarek R, et al. Comparison of hydrogen peroxide generation and the content of lipid peroxidation products in lung cancer tissue and pulmonary parenchyma. Respiratory Medicine. 2000;94:800-805
  42. 42. Cejas P, Casado E, Belda-Iniesta C, De Castro J, Espinosa E, Redondo A, et al. Implications of oxidative stress and cell membrane lipid peroxidation in human cancer (Spain). Cancer Causes & Control. 2004;15:707-719
  43. 43. Barrera G. Oxidative stress and lipid peroxidation products in cancer progression and therapy. International Scholarly Research Notices: Oncology. 2012:137289
  44. 44. Zhong H, Yin H. Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer: Focusing on mitochondria. Redox Biology. 2015;4:193-199
  45. 45. Van der Paal J, Neyts EC, Verlackt CCW, Bogaerts A. Effect of lipid peroxidation on membrane permeability of cancer and normal cells subjected to oxidative stress. Chemical Science. 2016;7:489-498
  46. 46. Marshall KA, Reist M, Jenner P, Halliwell B. The neuronal toxicity of sulfite plus peroxynitrite is enhanced by glutathione depletion: Implications for Parkinson’s disease. Free Radical Biology & Medicine. 1999;27:515-520
  47. 47. Beal MF. Oxidatively modified proteins in aging and disease. Free Radical Biology & Medicine. 2002;32:797-803
  48. 48. Vatassery GT, Lai JC, DeMaster EG, Smith WE, Quach HT. Oxidation of vitamin E and vitamin C and inhibition of brain mitochondrial oxidative phosphorylation by peroxynitrite. Journal of Neuroscience Research. 2004;75:845-853
  49. 49. Reynolds MR, Reyes JF, Fu Y, Bigio EH, Guillozet-Bongaarts AL, Berry RW, et al. Tau nitration occurs at tyrosine 29 in the fibrillar lesions of Alzheimers disease and other tautopathies. The Journal of Neuroscience. 2006;26:10636-10645
  50. 50. Sun GY, He Y, Chuang DY, Lee JC, Gu Z, Simonyi A, et al. Integrating cytosolic phospholipase A2 with oxidative/nitrosative signaling pathways in neurons: A novel therapeutic strategy for AD. Molecular Neurobiology. 2012;46:85-95
  51. 51. Rosselli M, Keller PJ, Dubey RK. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Human Reproduction Update. 1998;4:3-24
  52. 52. Lavi S, Egbarya R, Lavi R, Jacob G. Role of nitric oxide in the regulation of cerebral blood flow in humans: Chemoregulation versus mechanoregulation. Circulation. 2003;107:1901-1905
  53. 53. Knott AB, Bossy-Wetzel E. Nitric oxide in health and disease of the nervous system. Antioxidants & Redox Signaling. 2009;11:541-554
  54. 54. Radi E, Formichi P, Battisti C, Federico A. Apoptosis and oxidative stress in neurodegenerative diseases. Journal of Alzheimer’s Disease. 2014;42:125-152
  55. 55. Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biology. 2018;14:450-464
  56. 56. Panthi S, Manandhar S, Gautam K. Hydrogen sulfide, nitric oxide, and neurodegenerative disorders. Translational Neurodegeneration. 2018;7:3
  57. 57. Kim J, Kumar GS, Choi HW, Park D, Kim WJ. A platform for nitric oxide delivery. Journal of Materials Chemistry B. 2014;2:341-356
  58. 58. Pratico D, Uryu K, Leight S, Trojanoswki JQ , Lee VM. Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzeheimer amyloidosis. The Journal of Neuroscience. 2001;21:4183-4187
  59. 59. Singh RP, Sharad S, Kapur S. Free radicals and oxidative stress in neurodegenerative diseases: Relevance of dietary antioxidants. Journal, Indian Academy of Clinical Medicine. 2004;5:218-225
  60. 60. Xu Q , Huang Y. Lipid metabolism in Alzheimer’s and Parkinson’s disease. Future Lipidology. 2006;1:441-453
  61. 61. Reed TT. Lipid peroxidation and neurodegenerative disease. Free Radical Biology & Medicine. 2011;51:1302-1319
  62. 62. Chen X, Guo C, Kong J. Oxidative stress in neurodegenerative diseases. Neural Regeneration Research. 2012;7:376-385
  63. 63. Suridjan I, Herrmann N, Adibfar A, Saleem M, Andreazza A, Oh PI, et al. Lipid peroxidation markers in coronary artery disease patients with possible vascular mild cognitive impairment. Journal of Alzheimer’s Disease. 2017;58:885-896
  64. 64. Magalingam KB, Radhakrishnanm A, Ping NS, Haleagrahara N. Current concepts of neurodegenerative mechanisms in Alzheimer’s disease. BioMed Research International. 2018:3740461
  65. 65. Cannon RO. Role of nitric oxide in cardiovascular disease: Focus on the endothelium. Clinical Chemistry. 1998;44:1809-1819
  66. 66. Harrison D, Griendling KK, Landmesser U, Hornig B, Drexler H. Role of oxidative stress in atherosclerosis. The American Journal of Cardiology. 2003;91:7-11
  67. 67. Adachi T, Weisbrod RM, Pimentel DR, Ying J, Sharov VS, Schoneich C, et al. S-glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide. Nature Medicine. 2004;10:1200-1207
  68. 68. Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and oxidative stress in cardiovascular diseases. Circulation Journal. 2009;73:411-418
  69. 69. Antosova M, Plevkova J, Strapkova A, Buday T. Nitric oxide-important messenger in human body. Open Journal of Molecular and Integrative Physiology. 2012;2:98-106
  70. 70. Sack MN, Fyhrquist FY, Saijonmaa OJ, Fuster V, Kovacic JC. Basic biology of oxidative stress and the cardiovascular system: Part 1 of a 3-Part Series. Journal of the American College of Cardiology. 2017;70:196-211
  71. 71. Cervantes Gracia K, Llanas-Cornejo D, Husi H. CVD and oxidative stress. Journal of Clinical Medicine. 2017;6:22
  72. 72. Yuan T, Yang T, Chen H, Fu D, Hu Y, Wang J, et al. New insights into oxidative stress and inflammation during diabetes mellitus accelerated atherosclerosis. Redox Biology. 2018;20:247-260
  73. 73. Ahmad A, Dempsey SK, Daneva Z, Azam M, Li N, Li PL, et al. Role of nitric oxide in the cardiovascular and renal systems. International Journal of Molecular Sciences. 2018;19:E2605
  74. 74. Hogg N, Kalyanaraman B, Joseph J, Struck A, Parthasarathy S. Inhibition of low-density lipoprotein oxidation by nitric oxide. Potential role in atherogenesis. FEBS Letters. 1993;334:170-174
  75. 75. Ronson RS, Nakamura M, Vinten-Johansen J. The cardiovascular effects and implications of peroxynitrite. Cardiovascular Research. 1999;44:47-59
  76. 76. Ferdinandy P, Danial H, Ambrus I, Rothery RA, Schulz R. Peroxynitrite is a major contributor of cytokine-induced myocardial contractile failure. Circulation Research. 2000;87:241-247
  77. 77. Mihm MJ, Coyle CM, Schanbacher BL, Weinstein DM, Bauer JA. Peroxynitrite induced nitration and inactivation of myofibrillar creatine kinase in experimental heart failure. Cardiovascular Research. 2001;49:798-807
  78. 78. Brunner F, Wolkart G. Peroxynitrite-induced cardiac depression: Role of myofilament desensitization and cGMP pathway. Cardiovascular Research. 2003;60:355-364
  79. 79. Lokuta AJ, Maertz NA, Meethal SV, Potter KT, Kamp TJ, Valdivia HH, et al. Increased nitration of sarcoplasmic reticulum Ca2+-ATPase in human heart failure. Circulation. 2005;111:988-995
  80. 80. Radi R. Peroxynitrite, a stealthy biological oxidant. The Journal of Biological Chemistry. 2013;13:26464-26472
  81. 81. Campolo J, De Maria R, Caruso R, Accinni R, Turazza F, Parolini M, et al. Blood glutathione as independent marker of lipid peroxidation in heart failure. International Journal of Cardiology. 2007;117:45-50
  82. 82. Ramana KV, Srivastava S, Singhal SS. Lipid peroxidation products in human health and disease. Oxidative Medicine and Cellular Longevity. 2013:583438
  83. 83. Zhang PY, Xu X, Li XC. Cardiovascular diseases: Oxidative damage and antioxidant protection. European Review for Medical and Pharmacological Sciences. 2014;18:309-316
  84. 84. Ulintz L, Sun Q. Ambient particulate matter pollution on lipid peroxidation in cardiovascular diseases. Environmental Disease. 2016;1:109-117
  85. 85. Graham A, Hogg N, Kalyanaraman B, O’Leary V, Darley-Usmar V, Moncada S. Peroxynitrite modification of low-density lipoprotein leads to recognition by the macrophage scavenger receptor. FEBS Letters. 1993;330:181-185
  86. 86. Moilanen E, Vapaatalo H. Nitric oxide in inflammation and immune response. Annals of Medicine. 1995;27:359-367
  87. 87. Schopfer FJ, Baker PR, Freeman BA. NO-dependent protein nitration: A cell signalingeventoran oxidative inflammatory response? Trends in Biochemical Sciences. 2003;28:646-654
  88. 88. Bar-Shai M, Reznick AZ. Peroxynitrite induces an alternative NF-kappa B activation pathway in L8 rat myoblasts. Antioxidants & Redox Signaling. 2006;8:639-652
  89. 89. Tripathi P, Tripathi P, Kashyap L, Singh V. The role of nitric oxide in inflammatory reactions. FEMS Immunology and Medical Microbiology. 2007;51:443-452
  90. 90. Sharma JN, Al-Omran A, Parvathy SS. Role of nitric oxide in inflammatory diseases. Inflammopharmacology. 2007;15:252-259
  91. 91. Kawakami T, Koike A, Amano F. Sodium bicarbonate regulates nitric oxide production in mouse macrophage cell lines stimulated with lipopolysaccharide and interferon γ. Nitric Oxide. 2018;79:45-50
  92. 92. Zhan R, Wang F, Wu Y, Wang Y, Qian W, Liu M, et al. Nitric oxide induces epidermal stem cell deadhesion by targeting integrin β1 and Talin via the cGMP signalling pathway. Nitric Oxide. 2018;78:1-10
  93. 93. Brito C, Naviliat M, Tiscornia AC, Vuillier F, Gualco G, Dighiero G, et al. Peroxynitrite inhibits T lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and peroxynitrite-driven apoptotic death. Journal of Immunology. 1999;162:3356-3366
  94. 94. Ahmad R, Rasheed Z, Ahsan H. Biochemical and cellular toxicology of peroxynitrite: Implications in cell death and autoimmune phenomenon. Immunopharmacology and Immunotoxicology. 2009;31:388-396
  95. 95. Prolo C, Alvarez MN, Radi R. Peroxynitrite, a potent macrophage derived oxidizing cytotoxin to combat invading pathogens. BioFactors. 2014;40:215-225
  96. 96. Vara D, Pula G. Reactive oxygen species: Physiological roles in the regulation of vascular cells. Current Molecular Medicine. 2014;14:1103-11025
  97. 97. Morris G, Berk M. The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Medicine. 2015;13:68
  98. 98. Khan MA, Alam K, Zafaryab M, Rizvi MMA. Peroxynitrite-modified histone as a pathophysiological biomarker in autoimmune diseases. Biochimie. 2017;140:1-9
  99. 99. Radi R. Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine. Proceedings of the National Academy of Sciences. 2018;115:5839-5848
  100. 100. Tewthanom K, Janwityanuchit S, Totemchockchyakarn K, Panomvana D. Correlation of lipid peroxidation and glutathione levels with severity of systemic lupuserythematosus: A pilot study from single center. Journal of Pharmacy & Pharmaceutical Sciences. 2008;11:30-34
  101. 101. Otaki N, Chikazawa M, Nagae R, Shimozu Y, Shibata T, Ito S, et al. Identification of a lipid peroxidation product as the source of oxidation-specific epitopesrecognized by anti-DNA autoantibodies. The Journal of Biological Chemistry. 2010;285:33834-33842
  102. 102. Barrera G, Pizzimenti S, Daga M, Dianzani C, Arcaro A, Cetrangolo GP, et al. Lipid peroxidation-derived aldehydes, 4-hydroxynonenal and malondialdehyde in aging related disorders. Antioxidants. 2018;7:102
  103. 103. Walker LM, Walker PD, Imam SZ, Ali SF, Mayeux PR. Evidence for peroxynitrite formation in renal ischemia reperfusion injury; studies with the inducible nitric oxide synthase inhibitor L-N(6)-(1-Iminoethyl) lysine. The Journal of Pharmacology and Experimental Therapeutics. 2000;295:417-422
  104. 104. Modlinger PS, Wilcox CS, Aslam S. Nitric oxide, oxidative stress, and progression of chronic renal failure. Seminars in Nephrology. 2004;24:354-365
  105. 105. Liang JH, Li YN, Qi JS, Jia XX. Peroxynitrite induced protein nitration is pesponsible for renal mitochondrial damage in diabetic rat. Journal of Endocrinological Investigation. 2010;33:140-146
  106. 106. Chirino YI, Hernandez-Pando R, Pedraza-Chaverri J. Peroxynitrite decomposition catalyst ameliorates renal damage and protein nitration in cisplatin-induced nephtotoxicity in rats. BMC Pharmacology. 2004;4:20
  107. 107. Dennis JM, Witting PK. Protective role for antioxidants in acute kidney disease. Nutrients. 2017;9:718
  108. 108. Lau T, Owen W, Yu YM, Noviski N, Lyons J, Zurakowski D, et al. Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients. The Journal of Clinical Investigation. 2000;105:1217-1225
  109. 109. Klahr S. The role of nitric oxide in hypertension and renal disease progression. Nephrology, Dialysis, Transplantation. 2001;16:60-62
  110. 110. Goligorrsky MS, Brodsky SV, Noiri E. Nitric oxide in acute renal failure: NOS versus NOS. Kidney International. 2002;61:855-861
  111. 111. Meenakshi SR, Agarwal R. Nitric oxide levels in patients with chronic renal disease. Journal of Clinical and Diagnostic Research. 2013;7:1288-1290
  112. 112. Reddy YS, Kiranmayi VS, Bitla AR, Krishna GS, Srinivasa Rao PVLN, Sivakumar V. Nitric oxide status in patients with chronic kidney disease. Indian Journal of Nephrology. 2015;25:287-291
  113. 113. Ruan SY, Wu HY, Lin HH, Wu HD, Yu CJ, Lai MS. Inhaled nitric oxide and the risk of renal dysfunction in patients with acute respiratory distress syndrome: A propensity-matched cohort study. Critical Care. 2016;20:389
  114. 114. Ratliff BB, Abdulmahdi W, Pawar R, Wolin MS. Oxidant mechanisms in renal injury and disease. Antioxidants & Redox Signaling. 2016;25:119-146
  115. 115. Lei C, Berra L, Rezoagli E, Yu B, Dong H, Yu S, et al. Nitric oxide decreased acute kidney injury and stage 3 chronic kidney disease after cardiac surgery. American Journal of Respiratory and Critical Care Medicine. 2018;198:1279-1287
  116. 116. Sailaja Rao P, Sireesha K, Aparna Y, Sadanandam M. Free radicals and tissue damage: Role of antioxidants. Free Radicals and Antioxidants. 2011;1:1-7
  117. 117. Harsh M. Cell Injury and cellular adaptations. In: Textbook of Pathology. New Delhi: Jaypee Brothers Medical Publishers; 2010. pp. 21-34
  118. 118. Breen AP, Murphy JA. Reactions of oxyl radicals with DNA. Free Radical Biology & Medicine. 1995;18:1033-1077
  119. 119. Kumar V, Abbas AK, Fausto N. Cellular adaptations, cell injury and cell death. In: Robbins SL, Cotran RS, editors. Pathologic Basis of Disease. Philadelphia: Saunders; 2009. pp. 15-18
  120. 120. Agarwal HCLD, Gupta S. The role of free radicals and antioxidants in female infertility and assisted reproduction. US Genito-Urinary Disease. 2006:60-65
  121. 121. Arnold NO. Endogenous generation of singlet oxygen and ozone in human and animal tissues: Mechanisms, biological significance, and influence of dietary components. Oxidative Medicine and Cellular Longevity. 2016:1-22
  122. 122. Pryor WA, Houk KN, Foote CS, et al. Free radical biology and medicine: It’s a gas, man! The American Journal of Physiology-Regulatory Integrative and Comparative Physiology. 2006;291:R491-R511
  123. 123. Terao J, Minami Y, Bando N. Singlet molecular oxygenquenching activity of carotenoids: Relevance to protection of the skin from photoaging. Journal of Clinical Biochemistry and Nutrition. 2011;48(1):57-62
  124. 124. Smith lL. Oxygen, oxysterols, ouabain, and ozone: A cautionary tale. Free Radical Biology & Medicine. 2004;37:318-324
  125. 125. Balla J, Tyihak E. Direct measurement of emission of endogenous ozone from plants by GC-MS-SIM. Chromatographia. 2010;71:87-91
  126. 126. Rastogi RP, Richa AK, Tyagi MB, Sinha RP. Molecular mechanisms of ultraviolet radiation-induced DNA damage and repair. Journal of Nucleic Acids. 2010:1-32
  127. 127. Tyihak E, Oricz AMM, Ott PG. BioArena studies: Unique function of endogenous formaldehyde and ozone in the antibiotic effect—A review. Medicinal Chemistry. 2012;8:75-84
  128. 128. Wentworth P Jr, McDunn JE, Wentworth AD, et al. Evidence for antibody-catalyzed ozone formation in bacterial killing and inflammation. Science. 2002;298:2195-2199
  129. 129. Yamashita K, Miyoshi T, Arai T, et al. Ozone production by amino acids contributes to killing of bacteria. Proceedings of the National Academy of Sciences. 2008;105:16912-16917

Written By

Narendra Maddu

Submitted: September 15th, 2018 Reviewed: December 4th, 2018 Published: March 6th, 2019