Open access peer-reviewed chapter

Lipid Peroxidation: A Signaling Mechanism in Diagnosis of Diseases

Written By

Kalpana Sabanna Patil and Raju Ratan Wadekar

Submitted: 17 March 2021 Reviewed: 30 July 2021 Published: 26 August 2021

DOI: 10.5772/intechopen.99706

From the Edited Volume

Accenting Lipid Peroxidation

Edited by Pınar Atukeren

Chapter metrics overview

397 Chapter Downloads

View Full Metrics


Quantification of reactive oxygen species, is perplexing either in vivo or in vitro due to their short half-lives. Consequently, to define the magnitude of oxidative stress, the more stable oxidation products can be measured in biological samples. The oxidative stress leads to the lipid peroxidation that involves the initiation, termination and propagation of lipid radicals, wherein, the process involves the oxygen uptake, rearrangement of the double bonds in unsaturated lipids, that leads to polyunsaturated fatty acid deterioration. Subsequently, the toxic signaling end products are considered as biomarkers of free radicals that act both as signaling molecules and as cytotoxic products cause covalent alteration of lipid peroxidation products. The use of validated signaling mechanism (s) of Lipid peroxidation and products derived thereof exhibits its use clinical practice and basic clinical research as well as in clinical practice has become common place, and their presence as endpoints in clinical trials is now broadly accepted. This knowledge can be used to diagnose disease earlier, or to prevent it before it starts. The signaling markers can be used to excel the effectiveness of the prevailing medicines and to improve the new medicines.


  • lipid peroxidation
  • isoprostanes
  • malondialdehyde
  • Alzheimer’s disease
  • oxidative stress

1. Introduction

Lipids are of two types: Polar and Non-polar. The polar lipids (Triglycerides), store in various cells but especially in adipose (fat) tissue, are usually the main source of energy for mammals. Polar lipids are underlying segments of cell layers, where in it contributesfor thedevelopment of permeability barrier of cells and sub-cellular organelles in the form of a lipid bilayer [1]. The glycerol-based phospholipid is the significant type of membranous lipid bilayer and it is evidenced by the element that membrane lipids may regulates the biologicalfunctions of a membrane organelle by amending its biophysical characteristics, such as the divergence and absorptivity [2]. Lipids and its metabolite productsfacilitates a key ingredient in understanding the biology and serve as a signaling biomolecules in the diagnosis of diseases [3]. However, theleading enzymes that generate as lipid-signaling biomarkers are lipoxygenase, that intervene hydroperoxyeicosatetraenoic acids (HPETEs), lipoxins, leukotrienes, or hepoxilins biosynthesis after oxidation of fatty acids/arachidonic acid (AA), cyclooxygenase that yields prostaglandins, and cytochrome P-450 (CYP) that produces epoxyeicosatrienoic acids, leukotoxins, thromboxane, or prostacyclin respectively [4, 5]. The signaling lipid biomarkers recruitsvia stimulation of a variety of receptors, including nuclear and G protein-coupled receptors. Moreover, several othertypes of lipidmetabolites have been recognized as potent intracellular signal transduction molecules viz; i) diacylglycerol (DAG) and inositol phosphates (IPs) were derived from the phosphatidylinositol phosphates. DAG is a transcription nuclear factor-kB (NF-kB) which promotes cell survival and proliferation and also a physiological activator of protein kinase C [6, 7] and a small G protein [8]. On the other hand, IPs (lipid derived metabolites) are anextremelystimulatingthat intricate in signal transduction, results in activation of mTORand Akt [9], and calcium homeostasis [10, 11]; ii) Sphingolipid derived from ceramide (sphingosine-1-phosphate), is aeffective messenger molecule engaged in proliferation, adhesion, migration and alsoregulates calcium mobilization at molecular and cellular level of the organism [12, 13, 14]; iii) oxidative stress induced fatty acid derived eicosanoid and prostaglandins involved in inflammation [15, 16] and immunity [17]; iv) phosphotidylserine, (a phospholipid) that plays crucial role in a number of signaling pathways, includes fusogenic proteins, kinases and small GTPases [18]; v) the sex and growth hormones such as testosterone, progesterone, estrogen and cortisol that monitored a host body activities such as reproduction, blood pressure metabolism, inflammation, oxidative stress response etc. [19].

Molecular mechanism of lipid damage: The process of lipid peroxidation (LPO), is the resultant of oxidative stress and free radical production. Specifically, reactive oxygen species (ROS) attack polyunsaturated fatty acids (PUFAs) of cellular membranes and leads tothe insult of functional and/or structural integrity of cell membranes, subsequentlyproducing4-hydroxy-2-noneal (HNE), malondialdehyde (MDA) and acrolein (a group of α, β-unsaturated highly reactive aldehyde) [20, 21]. Therefore, these strong reactive aldehydes are significantlydiffusive, able to attack and form covalent linkages with auxiliary cellular constituents. Moreover, the lipid peroxidation process continues asself-propagation followed by initiation of chain reactions and termination either with complete substrate utilization or through interaction with antioxidants such as tocopherol (Vitamin E). Neuroprostanes (neuroPs), isoprostanes (IsoPs) are the additional LPO products of arachidonic acid and docosahexaenoic acid (DHA), that are quantified in the biological fluids to diagnose the severity of the disease. Furthermore, the cyclized fatty acids proliferate further and metabolize the cellular membrane components, mainly lipids and proteins, and propagates the other LPO products in the body fluids [22].

Quantification of reactive oxygen species, is perplexing either in vivo or in vitro due to their short half-lives. Consequently, to define the magnitude of oxidative stress, the more stable oxidation products can be measured in biological samples. The oxidative stress leads to the lipid peroxidation that involves the initiation, termination and propagation of lipid radicals, wherein, the process involves the oxygen uptake, rearrangement of the double bonds in unsaturated lipids, that leads to polyunsaturated fatty acid deterioration. Subsequently, the toxic signaling end products are considered as biomarkers of free radicals that act both as signaling molecules and as cytotoxic products cause covalent alteration of lipid peroxidation products [23]. In respect of their oxidative-induced damage properties, these compounds are considered as disease mediators in the pathophysiology of many neurodegenerative diseases (NDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), Diabetes, Atherosclerosis, Chronic inflammation, Asthma and liver injury that serve as potential biomarkers in the signaling mechanism in diagnosis of diseases [24]. Thus, it is necessary to understand the oxidative deterioration of lipids in a sequential five-step procedure in which oxidants, either radical or non-radical species, attack lipids containing C-C double bonds [25, 26]. On the contrary of enzyme-based lipid metabolism, lipid peroxidation does follow a non-enzymatic process that continues in ahystericalmode: Initiation, propagation and termination (Figure 1) [27].

Figure 1.

Oxidative deterioration of lipids.


2. Mechanism of action of lipid peroxidation (LPO)

The process of LPO on membrane influences discrete functions from the increased rigidity of membrane, reduced action of membrane-confined enzymes, impairment of membrane receptors and modified permeability of the cell membrane. Similar to phospholipid impairment, radicals can also directly attack lipid-protein and membrane proteins mediate as well as protein–protein interconnection, subsequently affect the membrane integrity [28]. LPO products persuade such a loss of membrane integrity that ultimately leads to unadorned cytotoxicity, and could result in unrestrained cellular growth or even apoptosis. Rationally, the perturbation of the above-mentioned functions ensued by polyunsaturated fatty acids, along with the resultant metabolites and protein insults modifies the neuronal homeostasis, and leads to the multi-organ organ dysfunction [29, 30, 31].


3. Lipid peroxidation (LPO) products as biomarkers in neurodegenerative disorders

LPO products are significantly associated to the development of Alzheimer’s diseases (AD); and hence, they are studied as potential disease signaling biomarkers in neurodegenerative disorders. LPO products such as MDA, IsoPs, TBARS, and fluorescent lipofuscin-like pigments (LPF) extensively studied and found in different human samples (plasma, serum and urine) of the patients suffering from neurodegenerative disorders. (Summarized in Table 1).

Sr. noBiomarkersBiological sampleAnalytical techniqueResultsReference
018-IsoprostaneUrineEIAAD <DrD*
02Isoprostanes oxidized LDLUrineELISANot differences between groups[33]
038-IsoprotanesSerumELISANon-frail AD < Pre-frail AD*[34]
04IsoprostanesUrineEIANon-frail AD < frail AD*[35]
05Isoprostanes, Neuroprostanes, dihomo-isoprostanesUrineRIAAD + placebo > AD treatment[36]
06MDAUrineGC–MSNot differences between groups after the treatment[37]
07MDAUrineUPLC-MS/MSSignificant differences in groups[38]
08MDAPlasmaHPLC-fluoresceaMCI converted >aMCI stable[39]
09MDABloodHPLC-MSMDA blood levels do not correlated with different cognitive tests[40]

Table 1.

Signaling mechanism of lipid peroxidation in biological samples of patients.

Histopathological studies revealed a co-localization of lipid peroxidation products and β-amyloidplaques in the brain of the AD. Also, the studiy evident for the presence of fatty acids in AD brain lesions produced a neurotoxic effect in cell culture increasing oxidative stress [41]. Since the brain contains high lipid content and high oxygen consumption, lipid peroxidation seems to play fundamental role in AD early detection. Similarly, IsoPsand its isomers produced via diverse actions that, are encountered as marginal oxidation products of the arachidonic acid [42]. Whereas, neuroPsenriched in the neuronal tissue and vital component of the nervous tissues, awfully susceptible to oxidation [43]. Thus, the quantitative estimation of neuroPsaffords a significantsource of oxidative neuronal impairmentcorresponding to IsoPs [44].

Malondialdehyde (MDA) a signaling molecule of LPO has ability to interact with micro-macromolecules such as nucleic acid bases, developingdivergent adducts, and can also react with proteins in a synergistic and covalent manner, subsequently, leads to the stimulation of strong immune responses and exhibits pro-fibrogenic and pro-inflammatory properties/mediators such as interleukins, cytokines etc. Furthermore, accumulation of MDA modifies membrane integrity by inducing increased intra and extracellular permeability and damage the fluidity of membrane lipid bilayer. Being a most mutagenic, MDA is capable of reacting with deoxyadenosine in DNA and deoxyguanosine, thus generating mutagenic DNA adducts [21, 31].

As the consequence of peroxidation of PUFAs (linoleic and arachidonic acid), Hudroxy-2-nonrenal (HNE) are formed, since they are the most abundant in fatty acids. The HNE, specifically, bind to amino acids mainly: cysteine, histidine and lysine proteinaceous residue addition by either the amino and thiol groups. The conjugates of protein residue and HNE, leads to the impairment of the normal protein function as well as structure, and also HNE exhibits reactivity with vital nucleic acids, lipids, signaling biomolecules and vitamins. Documented reports, suggests that, the HNE accumulates in extremely low concentration (10 μM), in response to oxidative stress and induces cytotoxicity and selective suppression of inducible and basal NF-kB factors. Therefore, increased levels of HNE results in Ca2+ homeostasisimbalance, disruption of glutamate transport, membrane impairment, microtubule function, and cellular death via the activation of caspase pathways [28, 45].

Threonine metabolite product, acrolein generated by the bio activation of phagocytes and cyclophosphamide. Wherein, acrolein targets histidyl, lysyl and cysteinyl residue of protein side chain as well as reactswith nucleophilic sites in DNA, that results in DNA and protein adducts and, thus, initiates cytotoxicity specifically related to its ability to reduce glutathione [46]. Docosahexaenoic acid (DHA) enriched in neurons, and is a vital compound of the nervous tissue. It is a vital compound of the nervous tissue and enriched in neurons and extremelysusceptible to oxidation. DHA on oxidative stress, leads to the production of Neuroprostanes (F4-isoprostanes). In a biological aspect, neuroPsillustrates anti-inflammatory properties by inhibiting proteasome concentrated in the neurons membrane [45]. Nevertheless, the central nervous system (CNS) is one of the major targets of the LPO and proneto chain reactions induced by ROS, which eventually result in LPO products [47]. The role of LPO quantification in the pathogenesis of NDs is significant and extremely importance for the early detection of neurodegenerative disorders [45].

The most frequently exploited LPO products such as lysine residues and unsaturated aldehydes, including HNE and aracolein [48]. Several research studies have been probing the LPO products and disease state interrelation, and its application as possible biomarkers in order to assess prognosis and establish early detection of the disease [49]. Among the above-mentioned potential biomarkers, IsoPssignifies the most reliable and robust outcomes. Moreover, the IsoPs accurately process and assessed the oxidant stress in vivovia quantification of plasma and urinary sample. Also, in situ phospholipids composed of IsoPs that locates the free radical production and release from the cellular membrane via phospholipases in the plasma. IsoPs detected and quantified in a plethora of biological fluids including plasma cerebrospinal fluid, exhaled breath condensate, urine and bile [50]. On the other hand, neuroPs are a fundamental component of the nervous tissue, enriched in the neuronal tissue and extremely susceptible to oxidation [51]. Thus, the quantification of neuroPs provides a signaling biomarker of oxidative neuronal damage compare to IsoPs quantification. In addition, the quantity of neuroPs produced from DHA surpass that of IsoPs from arachidonic acid by 3.4 folds. NeuroPsare elevated in the cerebrospinal fluid and brain tissue in ND, such as Parkinson and Alzheimer’s disease. Hence, quantification of neuroPs levels isa vital tool in evaluating brain oxidative impairment [52]. Whereas, crosslinking is a major factor in the development of pathology due to the promotion of intramolecular or intermolecular DNA and protein cross-linking, which results in intense change in the biochemical properties of various biomolecules (Figure 1). This articulated process is assumed to be a channel of interrelation chain reactions with covalent nucleophilic compounds. Also, the translated and interconnected experimental indicators with precise altered proteins in the CNS exhibited those definite cellular amendments are in concomitant with pathophysiology of Neurodegenerative diseases. Thus, the revival of scientific data affords a comprehensive knowledge in the advancement and employment of LPO products as potential biomarkers in the early diagnosis of the disease, alteredbiological processes, revealing potential active sites to target disease progression (Figure 2).

Figure 2.

Lipid peroxidation (LPO) products as biomarkers in neurodegenerative disorders.


4. Lipid peroxidation metabolites as influential signaling biomarkers in asthma and airway inflammation

Oxidative stress at molecular and cellular level can have many detrimental effects on airway function, including airway smooth muscle contraction, induction of airway hyper responsiveness, mucus hypersecretion, vascular exudation and shedding of epithelial cells. Furthermore, ROS can induce cytokine and chemokine production through induction of the oxidative stress-sensitive transcription of nuclear factor–kB in bronchial epithelial cells [53]. Recently discovered series of bioactive prostaglandin (PF)F2-like compoundswere produced independently of the cyclooxygenase enzymes via the peroxidation of arachidonic acid, catalyzed by free radicals. The pathway leads to formation of 64 isomeric structures, of which 8-iso-PGF2α is most well characterized. Evidence suggests that 8-iso-PGF 2α may act in part through the vascular thromboxane A2/PGH2 (TP) receptor [54]. 8-iso-PGF2α has been found to elicit airway hyper-responsiveness in isolated perfused mouse lungs, and cause airway obstruction and air plasma exudation in guinea pigs in vivo [55]. These experimental findings offerassumption about the contribution of Isoprostanes to the airway narrowing that is characteristic of asthma and in addition to being reliable signaling marker of lipid peroxidation, Isoprostane may prove to have an important biological role in the pathological of asthma. A significant elevation of reactive oxygen species, MDA formation (A product of Lipid peroxidation) and Isoprotane was estimated in the broncho-alveolar lavage (BAL) fluidwithin 24 hrs of allergen-induced asthma. This clearly indicates, Isoprotane is produce as a biomarker in respiratory tract tissues that leads to the late observed physical symptoms in allergen-induced asthma [56].

A recent study demonstrated that concentrations of exhaled ethane were increased in patients with more severe bronchoconstriction (forced expiratory volume in one second (FEV1) <60%), compared with less-constricted patients (FEV1 > 60%) and provides evidence that lipid peroxidation is related to asthma severity. These relationships between markers of oxidative stress and disease severity suggest that such tests may indicate the clinical status of asthma patients [57]. The increased level of 8-sio-PGF2α concentrations has been observed in chronic obstructive pulmonary diseases and asthma [58]. The discovery of Isoprostane has generated attention, as they provide a reliable index of oxidative stress in vivo. Isoprostane are structurally stable, are produced in vivo and are present in relatively high concentrations [59]. Traceable levels of F2-isoprostanes can be found in all normal animal and human biological fluids (including plasma, urine, bile, gastric juice, synovial fluid and cerebrospinal fluid)), and esterified in normal animal tissues. Thus, they overcome many of the methodological problems associated with other signaling markers. Determination of 8-iso-PGF2αas a marker of oxidative stress, of carbon tetrachloride (CCl4)-induced lipid peroxidation has been shown to be 20 times more sensitive than measurement of Thiobarbituric acid reactive substances (TBARS). Thus, the reliability of isoprostanes as in vivo markers of lipid peroxidation makes them an extremely valuable signaling biomarker for defining the potential of antioxidant agents (Vitamin C, E and β-carotene) in humans [60]. A significant amount of elevated ethane produced following lipid peroxidation has been observed in plasma and breath condensate of asthmatics as a biomarker indicator of acute airway inflammatory diseases. Moreover, measurement of auto-antibodies directed against oxidative modifications of low density lipids (LDL) is a recently developed technique that provides an in vivo marker of lipid peroxidation. Enzymes-linked immunosorbent assays are available in kit form, providing a quick and simple methodology. Thus measurement of isoprostanes in breath condensate should provide useful information concerning the degree of oxidant stress and success of antioxidant therapy in asthma (Figure 3).

Figure 3.

Lipid peroxidation metabolites as influential signaling biomarkers in lung diseases.


5. Lipid peroxidation: a signaling mechanism in diagnosis of liver injury

Oxidative stress is one of the mechanisms involved in the pathogenesis of drug-induced reactive oxygen species which lead to the depletion of intracellular antioxidants, causing an imbalance in the redox status of the hepatic cells [61]. Rapid, extensive lipid peroxidation of the membrane structural lipids due to oxidative stress mechanism involved in the pathogenesis of drug-induced had seen proposed as the basis of drug-induced hepatocellular toxicity. The most of the xenobiotics such as Acetaminophen, Isoniazid and Rifampicin are well-known to induced hepatic damage directly or indirectly via lipid peroxidation [62]. However, peroxy radical attribute to lipid peroxidation, thus known for the destabilization and disintegration of the cell membrane, that further causes arteriosclerosis, hepatic and kidney damage. The increased serum markers such as MDA formation are of diagnostic importance of hepatic injury because they are released due to the damage of hepatocytes and consequently participate in endogenous enzymatic antioxidant system imbalance [63]. CCl4-ehanced lipid peroxidation has been observed in liver tissue homogenates, isolated hepatocytes and in vivo, and this has been associated with changes in endoplasmic reticular enzyme activity, in vivo fatty acid export and protein synthesis [64]. CCL4 metabolism enhances production of malondialdehyde in vitro and increase ethane production and lethality in vivo (Figure 4). Consequently, lipid peroxidation initiated by free radical reactions and unchecked by compromised cellular defenses, provides a possible link between ethanol metabolism and associated liver disease [65]. The lipid peroxide content of liver is elevated by both short and long-term ethanol exposure and an enhanced rate of lipid peroxide formation following ingestion has been ascertained by MDA production, diene conjugate formation and in vivo ethane and pentane exhalation. Lipid peroxidation might merely be a sign of oxidative processes which occur after reduced glutathione is depleted concomitant with free radical attack on cellular protein and nucleic acid. The elevated MDA formation as a product of lipid peroxidation in drug-induced liver damage provide a significant biological signaling marker for the early detection or diagnosis of liver injury.

Figure 4.

Lipid peroxidation: a signaling mechanism in diagnosis of liver injury.


6. Conclusion

The oxidative stress inducing compounds mediates metabolic process of lipids mainly via peroxidation that leads to the production of macromolecules such as Isoprostane, MDA, 4-HNE in the biological fluids. Moreover, the aldehyde like molecules produced via lipid peroxidation targets and modifies proteins and DNA substantially at macromolecule level. Furthermore, MDA and 4-HNE known to promote cross linking of protein/DNA reactions that significantly alleviates and alters the biomarkers biochemical property, thereby develops a clinical symptomatic states. The use of validated signaling mechanism (s) of Lipid peroxidation and products derived thereof in basic and clinical research as well as in clinical practice has become common place, and their presence as endpoints in clinical trials is now broadly accepted. This knowledge can be used to diagnose disease earlier, or to prevent it before it starts. The signaling markers can be used to improve the efficacy and safety of existing medicines and to develop new medicines.


Conflict of interest

The authors declare no conflict of interest.


  1. 1. Frunbeck G, Gomez-Ambrosi J, Muruzabal FJ and Burrell MA. The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. The American Journal of Physiology: Endocrinology and Metabolism. 2001; 280:827-847.
  2. 2. Frayn KN. Regulation of fatty acid delivery in vivo. Advances in Experimental Medicine and Biology. 1998; 441: 171-179.
  3. 3. Vance E and Vance JE. Biochemistry: Biochemistry of Lipids, Lipoproteins and Membranes, 4th ed. 2002. p. : 144-155.
  4. 4. Massey KA and Nicolau A. Lipidomics of polyunsaturated fatty-acid-derived oxygenated metabolites. Biochemical Society Transactions. 2011; 39: 1240-1246.
  5. 5. Massey KA and Nicolaou A. Lipidomics of oxidized polyunsaturated fatty acids. Free Radical Biology and Medicine. 2013; 59:45-55.
  6. 6. Jornayvaz FR and Shulman GJ. Diacylglycerol activation of protein kinase CƐ and hepatic insulin resistance. Cell Metabolism. 2012; 15:574-584.
  7. 7. Giorgi C, Agnoletto C, Baldiniet al. Redox control of protein kinase C: cell and disease specific aspects. Antioxidants and Redox Signaling. 2010; 13: 1051-1085.
  8. 8. Yang C and Kazanietz MG. Chimaerins: GAPs that bridge diacylglycerolsignaling and the small G-protein Rac. Biochemical Journal. 2007; 403:1-12.
  9. 9. Baumann J, Sevinsky C and Conklin DS. Lipid biology of breast cancer. Biochimica Biophysica Acta. 2013; 1831:1509-1517.
  10. 10. Fisher SK, Novak JE and Agranoff BW. Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance. Journal of Neurochemistry. 2002; 82:736-754.
  11. 11. Conway SJ and Miller GJ. Biology-enabling inositol phosphates, phosphatidylinositol phosphates and derivatives. Natural Product Reports. 2007; 24:687-707.
  12. 12. Takuwa Y, Okamoto Y, Yoshioka K and Takuwa N. Sphingosine-1-phosphate signaling in physiology and diseases. Biofactor. 2012; 38:329-337.
  13. 13. Mattson MP. Membrane Lipid signaling in aging and age related disease. Elsevier. 2003;
  14. 14. Hannun YA and Obeid LM. Principles of bioactive lipid signaling lessons from sphingolipids. Nature Reviews Molecular Cell Biology. 2008; 9:139-150.
  15. 15. Aoki T and Narumiya S. Prostaglandins and chronic inflammation. Trends in Pharmacological Sciences. 2012; 33:304-311.
  16. 16. Tang EHC, Libby P, Vanhoutte PM and Xu A. Anti-inflammatory therapy by activation of prostaglandins EP4 receptor in cardiovascular and other inflammatory diseases. Journal of Cardiovascular Pharmacology. 2012; 59:116-123.
  17. 17. Kalinski P. Regulation of immune responses by prostaglandins E2. Journal of Immunology. 2012; 188:21-28.
  18. 18. Kay JG and Grinstein S. Phosphatidylserine-mediated cellular signaling. Advances in Experimental Medicine and Biology. 2013; 991:177-193.
  19. 19. Pluchino N, Russo M, Santoro P et al. Steroid hormones and BDNF. Neuroscience 2013; 239:271-279.
  20. 20. Signorini C, Felice DC, Durand T et al. Isoprostanes and 4-hydroxy-2-nonenal: markers or mediators of diseases? Focus on Rettsyndrome as a model of autism spectrum disorder Oxidative Medicinal Cell Longevity. 2013; 2013:343-824.
  21. 21. Erejuwa OO, Sulaiman SA, Wahab MS. Evidence in support of potential applications of lipid peroxidation products in cancer treatment. Oxidative Medicinal Cell Longevity. 2013; 2013:931-251.
  22. 22. Zarkovic K. 4-hydroxynenal and neurodegenerative diseases. Molecular Aspects of Medicine. 2003; 24:293-303.
  23. 23. Sultana R, Perluigi M, Allan BD. Lipid peroxidation triggers neurodegeneration: a redox proteomics view into the Alzheimer disease brain. Free Radical Biological Medicine. 2013; 3:157-169
  24. 24. Barrera G, Gentile F, Pizzimenti S, et al. Mitochondrial Dysfunction in Cancer and Neurodegerataive Diseases: Spotlight on Fatty Acid Oxidation and Lipid Peroxidation Products. Antioxidants (Basel). 2016; 5:1
  25. 25. Perluigi M, Coccia R, Butterfield DA. 4-Hydroxy-2-nonenal, a reactive product of lipid peroxidation, and neurodegenerative diseases: a toxic combination illuminated by redox proteomics studies. Antioxidant Redox Signal. 2012; 17:1590-1609.
  26. 26. Ayala A, Munoz MF, Arguelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicinal Cell Longevity. 2014; 2014:360-438.
  27. 27. Bradley-Whitman MA, Lovell MA. Biomarkers of lipid peroxidation in Alzheimer diseases (AD): an update. Archive Toxicology. 2015; 89:1035-1044.
  28. 28. Shoeb M, Ansari NH, Srivastava S., et al. 4-hydroxynonenal in the pathogenesis and progression of human diseases. Current Medicinal Chemistry. 2014; 21: 230-237.
  29. 29. Yadav UC, Ramana KV. Regulation of NF-kappaB-induced inflammatory signaling by lipid peroxidation-derived aldehydes. Oxidative Cell Longevity. 2013; 2013:1-13
  30. 30. Fritz KS, Petersen DR. An overview of the chemistry and biology of reactive aldehydes. Free Radical Biology medicine. 2013; 59:85-91.
  31. 31. Gueraud F, Atalay M, Bresgen N, et al. Chemistry and biochemistry of lipid peroxidation products. Free Radical Research. 2010; 44:1098-1124.
  32. 32. Hatanaka H, Hanyu H, Fukasava R, et al. Peripheral oxidative stress markers in diabetes-related dementia. Geriatric Gerontology International. 2016; 16:1312-1318.
  33. 33. Scheff SW, Ansari MA, Mufson EJ. Oxidative stress and hippocampal synaptic protein levels in early cognitively intact individuals with Alzheimer’s disease pathology. Neurobiological aging. 2016; 42:1-12.
  34. 34. Rubio Perez JM , et al. Effect of an antioxidant beverage on biomarkers of oxidative stress in Alzheimer’s patients. European Journal of Nutrition. 2016; 55:2105-2116.
  35. 35. Namioka N, Hanyu H, Hirose D, Hatanaka H, Sato T, Shimizu S. Oxidative stress and inflammatory are associated with physical frailty in patients with Alzheimer’s disease. Geriatric Gerontology International. 2017; 17: 913-918.
  36. 36. Freund-Levi Y, Vedin I, Hjorth E, et al. Effects of supplementation with omega-3-fatty acids on oxidative stress and inflammation in patients with Alzheimer’s disease: the omega AD study. Journal of Alzheimer’s Disease. 2014; 42:823-831.
  37. 37. Shinto L, Quinn J, Montine T, et al. A randomized placebo-controlled pilot trial of omega-3-fatty acids and alpha lipoic acid in Alzheimer’s disease. Journal of Alzheimer’s Disease. 2014; 38:111-120.
  38. 38. Rommer PS, Fuchs D, Leblhuber F, et al. Lowered levels of carbonyl proteins after vitamin B supplementation in patients with mild cognitive impairment and Alzheimer’s disease. Neurodegenerative Disease. 2016; 16:284-289.
  39. 39. Yuan L, Liu J, Ma W, et al. Dietary pattern and antioxidants in plasma and erythrocyte in patients with mild cognitive impairment from China. Nutrition. 2016; 32:193-198.
  40. 40. Gubandru M, Margina D, Tsitsimpikou C, et al. Alzheimer’s patients showed different patterns for oxidative stress and inflammation markers. Food Chemistry and Toxicology. 2013; 61:2019-2214.
  41. 41. Benseny-cases N, Klementieva O, Cotte M, et al. Microspectroscopy reveals co-localization of lipid oxidation and amyloid plaques in human Alzheimer’s disease brains. Analytical Chemistry. 2014; 86:12047-12054.
  42. 42. Zarrouk A, Nury T, Riedinger JM, et al. Effect of docosahexaenoic acid (attenuation or amplification) on C22:0-, C24:0-, and C26:0-induced mitochondrial dysfunctions and oxidative stress on human neuronal SK-N-BE cells. Journal of Nutrition Health and Aging. 2015; 19:198-205.
  43. 43. Choi J, Ravipati A, Nimmagadda V, et al. Potential roles of PINK1 for increased PGC-1α-mediated mitochondrial fatty acid oxidation and their associations with Alzheimer’s disease and diabetes, Mitochondrion. 2014; 18:41-48.
  44. 44. Bacchetti T, Vignini A, Giulietti A, et al. Higher levels of oxidized low density lipoproteins in Alzheimer’s disease patients: roles for platelet activiating factor acetyl hydrolase and paraxonase-1. Journal of Alzheimers Disease. 2015; 46:179-186.
  45. 45. Pizzimenti S, Ciamporcero E, Daga M, et al. Interaction of aldehydes derived from lipid peroxidation and membrane proteins. Frontiers Physiology. 2013; 4:242.
  46. 46. Reed TT. Lipid peroxidation and neurodegenerative disease. Free Radical Biology and Medicine. 2011; 51: 1302-1319.
  47. 47. Shichiri M. The role of lipid peroxidation in neurological disorders. Journal of Clinical Biochemistry and Nutrition. 2014; 54:151-160.
  48. 48. Magalingam KB. Radhakrishnana AK, Haleagrahran N. Protective mechanism of flavonoids in Parkinson’s disease. Oxidative Medicinal Cell Longevity. 2015; 2015: 1-13.
  49. 49. Pratico D. The neurobiology of isoprostanes and Alzheimer’s disease. Biochime Bipphys Acta. 2010; 1801:930-933.
  50. 50. Skoumalova A, Hort J. Blood markers of oxidative stress in Alzheimer’s disease. Journal of Cell Molecular Medicine. 2012; 16:2291-2300.
  51. 51. Chauhan V, Chauhan A. Oxidative stress in Alzheimer’s disease. Pathophysiology. 2006; 13:195-208.
  52. 52. Surendran S, Rajasankar S. Parkinson’s disease: oxidative stress and therapeutic approaches. Neurological Science. 2010; 31:531-540
  53. 53. Gaschler MM, Stockwell BR. Lipid peroxidation in cell death. Biochem Biophys Research Communication. 2017; 482:419-425.
  54. 54. Takahsaki K, Nammour TM, Fukunaga M, et al. Glomerular actions of a free radical generate novel prostaglandin, 8-epi-PGF2α, in rat. Evidence for interactions with thromboxane A2 receptors. Journal of Clinical Investigation. 1992; 90:136-141.
  55. 55. Kawikova I, Barners PJ, Takahashi T, et al. 8-epi-PGF2aplha, a novel monocylooxygenase-derived prostaglandin, constricts airways in vitro. American Journal of Respiratory Critical Care Medicine. 1996; 153:590-596.
  56. 56. Dworski R, Murray JJ, Roberts LJI, et al. Allergen-induced synthesis of F2-isoprostanes in atopic asthmatics. American Journal of Respiratory Critical Care Medicine. 1999; 160:1947-1951.
  57. 57. Paredi P, Kharitonov SA, Barnes PJ. Levation of echaled ethane concentration in asthma. Chest. 1997; 111:862-865.
  58. 58. Pratico D, Basili S, Vieri M, et al. Chronic Obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane G2a III, an index of oxidant stress. American journal of Respiratory critical care medicine. 1998; 158:1709-1714.
  59. 59. Award JA, Roberts LJ. A series of prostaglandins F2-like compounds are produced in vivo in humans by a non-cyclooxygenase: use as clinical indicators of oxidant damage. Gastroenterology Clinical. 1996; 25:409-427.
  60. 60. Roberts LJ, Morrow JD. The generation and actions of isoprostanes, Biochim Biophys Acta. 1997; 1345: 121-135.
  61. 61. Diane LT, Tak YA, Dean PJ. The pathophysiology Significance of lipid peroxidation in oxidative cell injury. Hepatology. 1987; 7:377-387.
  62. 62. Naik SR, Wadekar RR, Goud SS, et al. Ameliorative effects of Tricholepisglanerrima in experimentally induced hepatic damage in rats: Modulation of cytokines functions. Journal of Ethnopharmacology. 2015; 160: 164-172.
  63. 63. Wadekar RR and Patil KS. Amelioration of Trichosantheslobata in Paracetamol-induced Hepatic Damage in Rats: A Biochemical and Histopathological Evaluation. Journal of Natural Remedies. 2017; 17: 28-37.
  64. 64. Patil KS, Wadekar RR. Hepatoprotective activity of Uvarianarumin paracetamol-induced hepatic damage in rats: a biochemical and histopathological evaluation. International Journal of Pharmacognosy.2014;1:119-129.
  65. 65. Chao-Ling Y, Wen-Huang P, Chih-Ming H, et al. Hepatoprotective Mechanisms of Taxifolin on Carbon Tetrachloride induced Acute Liver Injury in Mice. Nutrient. 2019; 2019:1-7

Written By

Kalpana Sabanna Patil and Raju Ratan Wadekar

Submitted: 17 March 2021 Reviewed: 30 July 2021 Published: 26 August 2021