Yusoff et al. Their study indicates that clonidine in addition to its hypotensive effect enhances the level of antioxidant status and ameliorates the oxidative stress which could reduce the hypertension-induced heart damage in spontaneously hypertensive rats without or with L-NAME administration. Studies by P. These studies indicate that treatment of lutein along with multivitamin complex but not lutein alone substantially reduced VEGF levels and MMP-2 activity and ameliorated the retinal morphological alterations in the apoE null mice.
The research article by S. Sahreen et al. The results provide some evidence that the extracts of Rumex hastatus roots could have beneficial antioxidant properties in preventing free radical-mediated toxicities.
In the article by A. This is an interesting report on how the combination of metal treatments regulates cellular oxidative stress in vitro and in vivo conditions. Sano et al. The relation between fluoride intake and oxidative stress in salivary glands of rats was reported by P. Yamaguti et al. Especially, they demonstrate that the single administration of sodium fluoride in rats decreased super oxide dismutase while increased the LPO in the salivary glands as early as in four hours.
Interestingly, the oxidative stress induced by sodium fluoride is more in submandibular glands as compared to parotid glands. Luo et al. Results indicate that LPO regulates ulinastatin diminished burn-induced increase in vascular permeability and net fluid accumulation. This study suggests a potential small-volume fluid resuscitation strategy in combating with a major burn injury.
In the final research article of this issue, Z. Yiran et al. The exciting clinical study reported by C. Cipierre et al. In the same issue, C. In this pilot clinical study, authors found a relationship between blood malondialdehyde-hemoglobin adduct concentrations with neonatal morbidity in very low birth-weight infants. Results from these two manuscripts indicate the significance of early antioxidant treatment to decrease oxidative stress mediated problems in very low birth-weight infants.
Interconnections between the pathological conditions associated with the diabetes and cirrhosis patients were reported by R.
This study indicates that the levels of oxidative stress markers in the red blood cells of cirrhotic patients were significantly increased, whereas in the patients with coincidence of diabetes and cirrhosis oxidative response was partially reduced.
Interestingly, the levels of total phospholipids and cholesterol were enhanced in the patients with both pathologies but not in the patients with the single pathology. In another clinical study, D. Some isoprostanes exist free in human plasma, but most are esterified to lipids.
Isoprostanes can be accurately and sensitively measured by mass spectrometric techniques, so that steady-state levels in human body fluids can easily be detected [,,,].
Isoprostanes appear to turn over rapidly, being both metabolised and excreted [,,]. Several methodological questions relating to isoprostane analysis remain to be resolved reviewed in []. The question of confounding by oxidized lipids in the diet has been examined experimentally, and there is no evidence as yet that measurements of plasma isoprostanes in humans are so confounded [,,].
Most analyses of isoprostanes to date have focused on measurement of some of the F 2 -isoprostanes, which arise from the peroxidation of arachidonic acid residues []. Levels of certain F 2 -isoprostanes in human body fluids have been shown to be elevated in conditions that predispose to accelerated development of cardiovascular disease: diabetes [,] , hypercholesterolaemia [,] hyperhomocysteinaemia [] and cigarette smoking [,,]. Antioxidants have also been shown to decrease isoprostane levels in animals [,,—].
In studies on blood samples from human volunteers, plasma levels of F 2 -isoprostanes showed no correlation with levels of oxidative damage to DNA bases in white cells [] , suggesting that these two parameters are not determined by the same criteria. Indeed, whereas F 2 -isoprostane levels appear responsive to dietary antioxidants at least in subjects with elevated F 2 -isoprostane levels , levels of oxidative DNA damage generally are not see above. Effect of antioxidants on F 2 -isoprostane levels in human body fluids.
Another potential advantage of the isoprostanes is that different families are formed from different PUFAs [,—] , which gives a potential mechanism for following the rates of peroxidation of different PUFAs in vivo. It is well known that increasing unsaturation enhances the tendency of PUFAs to oxidize in vitro [9] , but the question of whether they peroxidize faster in vivo needs to be investigated using robust assays of lipid peroxidation.
Robust biomarkers of lipid peroxidation of which at the moment the best available seem to be the isoprostanes should be used to establish the effects of diet on lipid peroxidation in vivo, and in particular what contribution is made to any effect of diet by the antioxidants present in that diet ascorbate, vitamin E, carotenoids, flavonoids etc.
Any cardiovascular disease intervention trial that does take place should be accompanied by measurements of lipid peroxidation. Measurements of lipid peroxidation should be carried out:. Prior to the intervention study, to show in short-term studies that the intervention does actually decrease lipid peroxidation, preferably in a dose-dependent manner, in the subjects to be examined.
At intervals during the study, to relate changes in the levels of lipid peroxidation to clinical end-points. One further point may be important. Are those with high levels of lipid peroxidation more at risk of developing cardiovascular disease later in life, and would antioxidants help to prevent this [31,]?
The combination of excellent chemistry robust and validated biomarkers of oxidative damage with excellent epidemiology will be a powerful tool to answer these questions [31]. La Vecchia C. De Carli A. Pagano R. Vegetable consumption and risk of chronic disease Epidemiology 9 Google Scholar. Rimm E. Ascherio A. Giovannucci E. Spiegelman D. Stampfer M. Willett W. Vegetable, fruit and cereal fiber intake and risk of coronary heart disease among men J Am Med Assoc Lloyd T.
Chinchilli V. Rollings N. Singh R. Rastogi V. Rastogi S. Niaz M. Beegom R. Effect of diet and moderate exercise on central obesity and associated disturbances, myocardial infarction and mortality in patients with and without coronary artery disease J Am Coll Nutr 15 Renaud S. Guenguen R. The French paradox and wine drinking Novartis Foundation Symp De Lorgeril M.
Salen P. Martin J. Moniaud I. Delaye J. Mamelle N. Mediterranean diet, traditional risk factors and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart study Circulation 99 Albert C. Manson J. Cook N. Moderate alcohol consumption and the risk of sudden cardiac death among US male physicians Circulation Sesso H.
Gaziano J. Buring J. Hennekens C. Coffee and tea intake and the risk of myocardial infarction Am J Epidemiol Free radicals in biology and medicine, ed. Wiseman S. Balentine D. Frei B. Frankel E.
Waterhouse A. Teissedre P. Principal phenolic phytochemicals in selected California wines and their antioxidant activity in inhibiting oxidation of human low density lipoproteins J Agr Food Chem 43 Paganga G. Miller N. Rice-Evans C. The polyphenolic content of fruits and vegetables and their antioxidant activities.
What does a serving constitute? Free Rad Res 30 Gey K. Vitamins E plus C and interacting nutrients required for optimal health Biofactors 7 Lampe J. Health effects of vegetables and fruit: assessing mechanisms of action in human experimental studies Am J Clin Nutr 70 Suppl.
Rosenfeld M. Inflammation, lipids and free radicals: lessons learned from the atherogenic process Semin Reprod Endocrinol 16 Steinberg D. Lewis A. Oxidative modification of LDL and atherogenesis Circulation 95 Bolli R. Marban E. Molecular and cellular mechanisms of myocardial stunning Physiol Rev 79 Ferrari R. Agnoletti L. Comini L. Oxidative stress during myocardial ischaemia and heart failure Eur Heart J 19 Suppl. B B2 Pratico G. Iuliano L. Mauriello A. Localization of distinct F 2 -isoprostanes in human atherosclerotic lesions J Clin Invest Mallat Z.
Philip I. Lebret M. Stephens N. Parsons A. Schofield M. Hsieh T. Juan G. Darzynkiewicz Z. Pietinen P. Korhonen P. Intake of dietary fiber and risk of coronary heart disease in a cohort of Finnish men Circulation 94 Brouwer I. Van Dusseldorp M. West C. Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial J Nutr Woodside J.
Yarnell J. McMaster D. Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinaemia: a double-blind, randomised, factorial-design, controlled trial Am J Clin Nutr 67 Al-Abed Y. Mitsuhashi T. Inhibition of advanced glycation endproduct formation by acetaldehyde: role in the cardioprotective effect of ethanol Proc Natl Acad Sci USA 96 Kris-Etherton P.
Yu-Poth S. Ratcliffe H. Zhao G. Etherton T. Nuts and their bioactive constituents: effects on serum lipids and other factors that affect disease risk Am J Clin Nutr 70 Suppl. Albanes D. Beta-carotene and lung cancer: a case study Am J Clin Nutr 69 Halliwell B. Establishing the significance and optimal intake of dietary antioxidants: the biomarker concept Nutr Rev 57 Poulsen H.
Loft S. Prieme H. Oxidative DNA damage in vivo: relationship to age, plasma antioxidants, drug metabolism, glutathione-S-transferase activity and urinary creatinine excretion Free Rad Res 29 Thorling E. Asami S. Hirano T. Yamaguchi R. Itoh H. Kasai H. Deng X. Tuo J. Okamura K. Doi T. Sakurai M. Effect of endurance exercise on the tissue 8-hydroxydeoxyguanosine content in dogs Free Rad Res 26 Rehman A.
Bourne L. Beatty E. England T. Geissler C. Aruoma O. Thompson H. Heimendinger J. Haegele A. Effect of increased vegetable and fruit consumption on markers of oxidative cellular damage Carcinogenesis 20 Smith M.
Inserra P. Watson R. Wise J. Supplementation with fruit and vegetable extracts may decrease DNA damage in the peripheral lymphocytes of an elderly population Nutr Res 19 Klaunig J. Gan C. The effect of tea consumption on oxidative stress in smokers and nonsmokers Proc Soc Exp Biol Med Pool-Zobel B. Bub A. Muller H.
Wollowski I. Rechkemmer G. Consumption of vegetables reduces genetic damage in humans: first results of an intervention trial with carotenoid-rich foods Carcinogenesis 18 Hernan M. The role of antioxidants in preventive cardiology Curr Opin Cardiol 12 Liu S. Ajani U. Chae C. Tornwall M. Virtamo J. Haukka J. Klipstein-Grobusch K. Geleijnse J. Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam study Am J Clin Nutr 69 Ness A.
Chee D. Elliott P. Vitamin C and blood pressure — an overview J Human Hypertens 11 Bates C. Walmsley C. Prentice A. Finch S. Does vitamin C reduces blood pressure?
Results of a large study of people aged 65 or older J Hypertens 16 Aminbakhsh A. Mancini J. Chronic antioxidant use and changes in endothelial dysfunction: a review of clinical investigations Can J Cardiol 15 Ceriello A. Vitamin C and endothelial dysfunction: what is new?
Circulation 99 Duffy S. Gokce N. Holbrook M. Treatment of hypertension with ascorbic acid Lancet Hinz B. Schroder H. Kushi L. Brown M. Do vitamin E and fish oil protect against ischaemic heart disease? Lancet Stahl W. Junghans A. Driomina E. Briviba K. Sies H. Consequently, these strong reactive aldehydes are greatly diffusive and capable of attacking or forming covalent linkages with farther cellular constituents 5. Ensuing this process, LPO continues self-propagation and initiation of chain reactions that are terminated either with complete substrate utilization or via interaction with antioxidants such as vitamin E 3 , 5.
These cyclized fatty acids proliferate further, attacking cellular membrane components, mainly lipids and proteins, and propagating other LPO products 4 , 5.
Quantification of ROS, either in vivo or in vitro , is challenging due to their short half-lives 6. Thus, oxidation products are, instead, quantified in biological samples, in which the magnitude of oxidative stress is quantifiable by measuring the more stable oxidation products 5 , 7. The role of LPO in the pathogenesis of these neurodegenerative disorders has been substantially founded, since markers of oxidative impairment have been identified in elevated levels in brain tissues and bodily fluids, suggesting their dual role as both disease mediators and potential biomarkers 7.
The aim of the present review is to describe LPO process and its products, and to characterize their role as potential biomarkers in NDs. LPO indicates the oxidative deterioration of lipids occurring via a five-step sequential procedure and can be generally described as an event in which oxidants, either radical or non-radical species, attack lipids containing C-C double bonds 9 , Contrary to enzymatic lipid metabolism, lipoid peroxidation is a non-enzymatic process that proceeds in an uncontrolled manner via three distinctive phases, i.
In this phase, the peroxyl radical abstracts a further H allylic atom, through which a self-sustained chain reaction is triggered, leading to the amplification of the initial oxidative event 9 , These aldehydes induce irreversible alteration of phospholipids, proteins, and DNA, leading to functional impairment as cyclic peroxides ascent to neuroprostanes and isoprostanes 9.
Following that step, the fourth step involves the termination of lipoid peroxidation; in which horizontal interplay among dissimilar types of radicals obstruct the chain reaction cascade 8 , 9.
Eventually, in the fifth step, termination occurs via interaction between radicals and antioxidants, resulting in the production of non-reactive radicals, or non-radical products 5 , 9 , In the termination process, antioxidants can be of either exogenous or endogenous nature 9 , 12 , These include vitamin E and C, which act by abating the generation of LPO at the initial stages of the free radical attack, operating as chain breaking antioxidants 9 , 14 Figure 1.
Membrane LPO influences numerous functions leading to elevated membrane rigidity, diminished action of membrane-confined enzymes, damage of membrane receptors and modified permeability of the cell membrane 7 , Similar to phospholipid impairment, radicals can directly attack membrane proteins and mediate lipid-protein as well as protein-protein interconnection, which additionally affect membrane integrity 7 , Out of all these events, LPO products induce such a loss of membrane integrity that eventually leads to loss of cellular function and severe cytotoxicity, and could result in uncontrolled cellular growth or even apoptosis 2 , 3 , 13 , Reasonably, the perturbation of the aforementioned functions occurred by PUFAs, together with the consequent metabolites and protein modifications disturb the neuronal homeostasis, thus, leading to brain dysfunction 7 , Additionally, MDA can be a consequence of prostaglandin breakdown by the cyclooxygenase activity, or via various non-lipid precursors, involving amino acids and carbohydrates that are able to produce MDA 5 , MDA is capable of interacting with nucleic acid bases, forming dissimilar adducts, and can also react with proteins in a synergistic and covalent manner, eventuating in stable protein adducts that further result in the induction of strong immune responses and exhibit pro-fibrogenic and pro-inflammatory properties 14 , Furthermore, assemblage of MDA is able to modify membrane permeability and deteriorate the fluidity of membrane lipid bilayer 5 , More specifically, HNE is able to bind to cysteine, histidine and lysine proteinaceous residues via Michael addition by either the amino -NH 2 or thiol -SH groups 5 , This aldehyde is highly electrophilic and capable of reacting with DNA, proteins and glutathione, exhibiting a hydrophobic nature 9 , Protein residues, bound to HNE, can damage normal protein function as well as structure, and HNE exhibits reactivity with vital cellular components including nucleic acids, lipids, signaling molecules and vitamins 5 , 15 , Due to its electrophilic properties, HNE possesses the potential of involvement in modulating enzyme action, gene expression and signal transduction, while its adducts contribute to enzyme damage that is elevated during aging and in specific pathological conditions 4 , 12 , Specifically, HNE interacts and interferes with normal cellular activities involving glucose uptake at synapses further contributing to synaptic deterioration, while it also induces loss of organelle function, e.
Antithetically, even diminished grades of HNE are able to increase and modify susceptibility of proteolysis and removal via the proteasomal system 9 , Acrolein is the most reactive product of LPO and exhibits a structure with three C atoms and a double bond 14 , In addition to PUFAs, acrolein is generated by threonine metabolism of activated phagocytes and cyclophosphamide bio-activation 5 , More specifically, acrolein is an electrophilic compound that binds or interacts extremely rapidly with fundamental cellular enzymes and nucleophiles, leading to their deactivation or deficiency 5 , Moreover, acrolein reacts with nucleophilic sites in DNA and proteins, leading to the formation of DNA and protein adducts and, thus, exerting cytotoxicity primarily related to its ability to diminish glutathione, 5.
Moreover, targets of acrolein in proteins involve the side chains of histidyl, lysyl, and cysteinyl residues as well as free N-terminal amino groups 5 , 14 , Cysteinyl residues are encountered in the active sites of proteins and are implicated in the catalytic action of enzymes; therefore, the formation of acrolein-cysteine adducts present a wide spectrum of functional implications This interaction causes alteration of cysteinyl residues that further cause inactivation of enzymes 14 - Broadly, acrolein is capable of inducing cellular degeneration and death, and particularly deterioration of hippocampal neurons 5.
The isoprostanes IsoPs also indicated as F2-isoprostanes, are prostaglandin-resembling compounds generated via free radical-compelled oxidation of arachidonic acid and further discharged from membrane phospholipids via phospholipases IsoPs exhibit a stable nature when detected in biological samples, while their aggregation can impair the integrity and fluidity of cellular membranes 14 - Similar to prostaglandins, they possess a fundamental action in cellular proliferation, platelet function, nociception, and smooth muscle contraction Neuroprostanes NeuroPs , or also annotated as F4-isoprostanes, are produced by free radicals catalyzing oxidation of docosahexaenoic acid DHA 5.
DHA is a vital compound of the nervous tissue, greatly enriched in neurons and profoundly vulnerable to oxidation 4. In a biological aspect, neuroPs depict anti-inflammatory properties while inhibiting proteasome activity Additionally, neuroPs are abundantly concentrated in the neuronal membranes The central nervous system CNS is one the major targets of the LPO, actually being particularly vulnerable, since the composition of neuronal tissue is susceptible to chain reactions moderated by free radicals, which eventually result in LPO products 7 ,
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