The Role of Glutathione Pathways in the Prevention of Atherosclerosis

  • Jordan L. Holtzman

Our current concept of the etiology of atherosclerosis is that it is a chronic inflammatory process. In support of this model serum markers of inflammation, such as high levels of C-reactive protein and fibrinogen, have been observed in numerous studies to be sensitive predictors of future cardiovascular adverse events. These markers are a group of serum proteins that are termed “acute phase reactants.” Their serum levels increase in the presence of any inflammatory process, the most common of which are infections. And indeed it has been suggested that atherosclerosis may be due to a focus of infection, such as periodontal disease. The infection then presumably spreads to the vascular tissues to initiate a local inflammatory process. Against this model it has been found in clinical trials that antibiotics do not prevent adverse vascular events. Furthermore, agents, such as statins, which have no antibacterial activity, have been shown in innumerable studies to be highly effective in the reduction of number of vascular events occuring in a vulnerable population. The apparent association between periodontal and vascular disease may be due to the fact that both conditions are much more common in smokers.


Glutathione Peroxidase Acute Myocardial Infarction Oxidant Injury Lipid Hydroperoxide Glutathione Peroxidase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Abu-Amero KK, Al-Boudari OM, Mohamed GH, Dzimiri N. T null and M null genotypes of the glutathione S-transferase gene are risk factor for CAD independent of smoking. BMC Med Genet 2006;7:38–45.PubMedCrossRefGoogle Scholar
  2. 2.
    Abou-Seif MA. Youssef AA. Evaluation of some biochemical changes in diabetic patients. Clin Chim Acta 2004;346:161–170.Google Scholar
  3. 3.
    Akcay T, Dincer Y, Kayali R, Colgar U, Oral E, Cakatay U. Effects of hormone replacement therapy on lipid peroxides and oxidation system in postmenopausal women. J Toxicol, Environ Health 2000;59:1–5.CrossRefGoogle Scholar
  4. 4.
    Albert MA, Ridker PM. The role of C-reactive protein in cardiovascular disease risk. Curr Cardiol Rep 1999;1:99–104.PubMedCrossRefGoogle Scholar
  5. 5.
    Agachan B, Yilmaz H, Ergen HA, Karaali ZE, Isbir T. Paraoxonase (PON1) 55 and 192 polymorphism and its effects to oxidant-antioxidant system in turkish patients with type 2 diabetes mellitus. Physiol Res 2005;54:287–93.PubMedGoogle Scholar
  6. 6.
    Alfthan G, Pekkanen J, Jauhiainen M, Pitkaniemi J, Karvonen M, Tuomilehto J, Salonen JT, Ehnholm C. Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population based study. Atherosclerosis 1994;106:9–19.PubMedCrossRefGoogle Scholar
  7. 7.
    Ambrosone CB, Coles BF, Freudenheim JL, Shields PG. Glutathione-S-transferase (GSTM1) genetic polymorphisms do not affecthuman breast cancer risk, regardless of dietary antioxidants. J Nutr 1999;129(2S Suppl):565S–568S.Google Scholar
  8. 8.
    Anderson ME, Meister A. Dynamic state of glutathione in blood plasma. J Biol Chem 1980;255:9530–9533.PubMedGoogle Scholar
  9. 9.
    Armstrong RN. Glutathione S-transferase: Reaction mechanism, structure and function. Chem Res Toxol 1991;4:131–140.CrossRefGoogle Scholar
  10. 10.
    Arosio E, De Marchi S, Zannoni M, Prior M, Lechi A. Effect of glutathione infusion on leg arterial circulation, cutaneous microcirculation, and pain-free walking distance in patients with peripheral obstructive arterial disease: a randomized, double-blind, placebo-controlled trial. Mayo Clinic Proc 2002;77(8):754–759.CrossRefGoogle Scholar
  11. 11.
    Arthur JR. The glutathione peroxidases. Cell Mol Life Sci 2000;57:1825–1835.PubMedCrossRefGoogle Scholar
  12. 12.
    Asayama K, Shiki Y, Ito H, Hasegawa O, Miyao A, Hayashibe H, Dobashi K, Kato K. Antioxidant enzymes and lipoperoxide in blood in uremic children and adolescents. Free Rad Biol Med 1990;9:105–109.PubMedCrossRefGoogle Scholar
  13. 13.
    Ashfaq S, Abramson JL, Jones DP, Rhodes SD, Weintraub WS, Hooper WC, Vaccarino V, Harrison DG, Quyyumi AA. The relationship between plasma levels of oxidized and reduced thiols and early atherosclerosis in healthy adults. J Am College Cardiol 2006;47: 1005–1011.CrossRefGoogle Scholar
  14. 14.
    Aviram M, Billecke S, Sorenson R, Bisgaier C, Newton R, Rosenblat M, Erogul J, Hsu C, Dunlop C, La Du B. Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different from that required for its arylesterase/paraoxonase activities: selective action of human paraoxonase allozymes Q and R. Arterioscler Thromb Vasc Biol 1998;18:1617–1624.PubMedGoogle Scholar
  15. 15.
    Aviram M, Fuhrman B. LDL oxidation by arterial wall macrophages depends on the oxidative status in the lipoprotein and in the cells: role of prooxidants vs. antioxidants. Molec Cellular Biochem 1998;188:149–159.CrossRefGoogle Scholar
  16. 16.
    Aviram M. Macrophage foam cell formation during early atherogenesis is determined by the balance between pro-oxidants and anti-oxidants in arterial cells and blood lipoproteins. Antioxidants Redox Signal 1999;1:585–594.CrossRefGoogle Scholar
  17. 17.
    Bednarek-Tupikowska G, Bohdanowicz-Pawlak A, Bidzinska B, Milewicz A, Antonowicz-Juchniewicz J, Andrzejak R. Serum lipid peroxide levels and erythrocyte glutathione peroxidase and superoxide dismutase activity in premenopausal and postmenopausal women. Gynec Endocrin 2001;15:298–303.Google Scholar
  18. 18.
    Belch JJF, Chopra M, Hutchison S, Lorimer R, Sturrock RD, Forbes CD, Smith WE. Free radical pathology in chronic arterial disease. Free Radical Biol Med 1989;6:375–378.CrossRefGoogle Scholar
  19. 19.
    Benditt EP, Benditt JM. Evidence for a monoclonal origin of human atherosclerotic plaques. Proc Nat Acad Sci USA 1973;70:1753–1756.PubMedCrossRefGoogle Scholar
  20. 20.
    Bjornstedt M, Xue J-Y, Huang W-H, Akesson B, Holmgren A. The thioredoxin and glutaredoxin systems are efficient electrons donors to human plasma glutathione peroxidase. J Biol Chem 1994;269:29382–29384.PubMedGoogle Scholar
  21. 21.
    Blankenberg S, Rupprecht HJ, Bickel C, Torzewski M, Hafner G, Tiret L, Smeija M, Cambien F, Meyer J, Lackner KJ. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Eng J Med 2003;349:1605–1613.CrossRefGoogle Scholar
  22. 22.
    Blann AD, Maxwell SR, Burrows G, Miller JP. Antioxidants, von Willebrand factor and endothelial cell injury in hypercholesterolaemia and vascular disease. Atherosclerosis 1995;116:191–198.PubMedCrossRefGoogle Scholar
  23. 23.
    Bond JA, Yang H-YL, Majesky MW, Benditt Juchau MR. Metabolism of benzo[a]pyrene and 7, 12-dimethylbenz[a]anthracene in chicken aortas: monooxygenation, bioactivation to mutagens, and covalent binding to DNA in vitro. Toxicol Appl Pharmacol 1980;52:323–335.PubMedCrossRefGoogle Scholar
  24. 24.
    Bor MV, Cevik C, Uslu I, Guneral F, Duzgun E. Selenium levels and glutathione peroxidase activities in patients with acute myocardial infarction. Acta Cardiol 1999;54:271–276.PubMedGoogle Scholar
  25. 25.
    Bowry VW, Stanley KK, Stocker R. High density lipoprotein is the major carrier of lipid hydroperoxides in human blood plasma from fasting donors. Proc Natl Acad Sci USA 1992;89:10316–10320.PubMedCrossRefGoogle Scholar
  26. 26.
    Brockmoller J, Kerb R, Drakoulis N, Staffeldt B, Roots I. Glutathione S-transferase M1 and its variants A and B as host factors of bladder cancer susceptibility: A case-control study. Cancer Res 1994;54:4103–4111.PubMedGoogle Scholar
  27. 27.
    Brockmoller J, Cascorbi I, Kerb R, Sachse C. Roots I. Polymorphisms in xenobiotic conjugation and disease predisposition. Toxicol Lett 1998;102–103:173–183.Google Scholar
  28. 28.
    Brockmoller J, Cascorbi I, Henning S, Meisel C, Roots I. Molecular genetics of cancer susceptibility. Pharmacology 2000;61:212–227.PubMedCrossRefGoogle Scholar
  29. 29.
    Cals MJ, Succari M, Meneguzzer E, Ponteziere C, Bories PN, Devanlay M, Desveaux N, Gatey M, Luciani L, Blonde-Cynober F, Coudray-Lucas C. Markers of oxidative stress in fit, health-conscious elderly people living in the Paris area. The Research Group on Ageing. Nutrition 1997;13:319–326.PubMedGoogle Scholar
  30. 30.
    Ceballos-Picot I, Witko-Sarsat V, Merad-Boudia M, Nguyen AT, Thevenin M, Jaudon MC, Zingraff J, Verger C, Jungers P, Descamps-Latscha B. Glutathione antioxidant system as a marker of oxidative stress in chronic renal failure. Free Rad Biol Med 1996;21:845–853.PubMedCrossRefGoogle Scholar
  31. 31.
    Chen N-Q, Liu Y-X, Greiner CD, Holtzman JL. Physiological Concentrations of Homocysteine Inhibit the Human, Plasma GSH-Peroxidase Which Reduces Organic Hydroperoxides. J Lab Clin Med 2000;136:58–65.PubMedCrossRefGoogle Scholar
  32. 32.
    Cheng L, Sturgis EM, Eicher SA, Char D, Spitz MR, Wei Q. Glutathione-S-transferase polymorphisms and risk of squamous-cell carcinoma of the head and neck. Int J Cancer (Pred Oncol) 1999;84:220–224.CrossRefGoogle Scholar
  33. 33.
    Child DF, Hudson PR, Jones H, Davies GK, De P, Mukherjee S, Brain AM, Williams CP, Harvey JN. The effect of oral folic acid on glutathione, glycaemia and lipids in Type 2 diabetes. Diab Nutr Metab 2004;17:95–102.Google Scholar
  34. 34.
    Colak E, Majkic-Singh N, Stankovic S, Sreckovic-Dimitrijevic V, Djordjevic PB, Lalic K, Lalic N. Parameters of antioxidative defense in type 2 diabetic patients with cardiovascular complications. Ann Med 2005;37:613–620.PubMedCrossRefGoogle Scholar
  35. 35.
    Cotton SC, Sharp L, Little J, Brockton N. Glutathione S-transferase polymorphisms and colorectal cancer: a HuGE review. Am J Epidemiol 2000;151:7–32.PubMedGoogle Scholar
  36. 36.
    Darley-Usmar VM, Severn A, O’Leary VJ, Rogers M. Treatment of macrophages with oxidized low-density lipoprotein increases their intracellular glutathione content. Biochem J 1991;278:429–434.PubMedGoogle Scholar
  37. 37.
    de Bruin WCC, Wagenmans MJM, Board PG, Peters WHM. Expression of glutathione S-transferase r class isoenzymes in human colorectal and gastric cancers. Carcinogenesis 1999;20:1453–1457.PubMedCrossRefGoogle Scholar
  38. 38.
    De Flora S, Izzotti A, Walsh D, Degan P, Petrilli GL, Lewtas J. Molecular epidemiology of atherosclerosis. FASEB J 1997;11:1021–1031.PubMedGoogle Scholar
  39. 39.
    de Haan JB, Witting PK, Stefanovic N, Pete J, Daskalakis M, Kola I, Stocker R, Smolich JJ. Lack of the antioxidant glutathione peroxidase-1 does not increase atherosclerosis in C57BL/J6 mice fed a high-fat diet. J Lipid Res 2006;47:1157–1167.PubMedCrossRefGoogle Scholar
  40. 40.
    De Mattia G, Bravi MC, Laurenti O, Cassone-Faldetta M, Proietti A, De Luca O, Armiento A, Ferri C. Reduction of oxidative stress by oral N-acetyl-L-cysteine treatment decreases plasma soluble vascular cell adhesion molecule-1 concentrations in non-obese, non-dyslipidaemic, normotensive, patients with non-insulin-dependent diabetes. Diabetologia 1998;41:1392–1396.PubMedCrossRefGoogle Scholar
  41. 41.
    de Waart FG, Kok FJ, Smilde TJ, Hijmans A, Wollersheim H, Stalenhoef AF. Effect of glutathione S-transferase M1 genotype on progression of atherosclerosis in lifelong male smokers. Atherosclerosis 2001;158:227–231.PubMedCrossRefGoogle Scholar
  42. 42.
    Diaz MN, Frei B, Vita JA, Keaney Jr. JF. Antioxidants and atherosclerotic heart disease. N Engl J Med 1997;337:408–414.PubMedCrossRefGoogle Scholar
  43. 43.
    Dogru-Abbasoglu S, Kanbagli O, Bulur H, Babalik E, Ozturk S, Aykac-Toker G, Uysal M. Lipid peroxides and antioxidant status in serum of patients with angiographically defined coronary atherosclerosis. Clin Biochem 1999;32:671–672.PubMedCrossRefGoogle Scholar
  44. 44.
    Dominguez C, Ruiz E, Gussinye M, Carrascosa A. Oxidative stress at onset and in early stages of type 1 diabetes in children and adolescents. Diabetes Care 1998;21:1736–1742.PubMedCrossRefGoogle Scholar
  45. 45.
    Doney AS, Lee S, Leese GP, Morris AD, Palmer CN. Increased cardiovascular morbidity and mortality in type 2 diabetes is associated with the glutathione S transferase theta-null genotype: a Go-DARTS study. Circulation 2005;111:2927–2934.PubMedCrossRefGoogle Scholar
  46. 46.
    Dubois-Rande JL, Artigou JY, Darmon JY, Habbal R, Manuel C, Tayarani I, Castaigne A, Grosgogeat Y. Oxidative stress in patients with unstable angina. Eur Hrt J 1994;15: 179–183.Google Scholar
  47. 47.
    Dwivedi VK, Chandra M, Misra PC, Misra A, Misra MK. Status of some free radical scavenging enzymes in the blood of myocardial infarction patients. J Enzyme Inhib Med Chem 2006;21:43–46.PubMedCrossRefGoogle Scholar
  48. 48.
    Efe H, Deger O, Kirci D, Karahan SC, Orem A, Calapoglu M. Decreased neutrophil antioxidative enzyme activities and increased lipid peroxidation in hyperlipoproteinemic human subjects. Clinica Chimica Acta 1999;279:155–165.CrossRefGoogle Scholar
  49. 49.
    Efe H, Kirci D, Deger O, Yildirmis S, Uydu HA, Orem C. Erythrocyte antioxidant enzyme activities and lipid peroxidation in patients with types IIb and IV hyperlipoproteinemias. Tohoku J Exp Med 2004;202:163–172.PubMedCrossRefGoogle Scholar
  50. 50.
    Ehara S, Ueda M, Naruko T, Haze K, Itoh A, Otsuka M, Komatsu R, Matsua T, Itabe H, Takano T, Tsukamoto Y, Yoshiyama M, Takeuchi K, Yoshikawa J, Becker A.E. Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 2001;103:1955–1960.PubMedGoogle Scholar
  51. 51.
    Emdin M, Pompella A, Paolicchi A. Gamma-glutamyltransferase, atherosclerosis, and cardiovascular disease: triggering oxidative stress within the plaque. Circulation 2000;112: 2078–2080.CrossRefGoogle Scholar
  52. 52.
    Esworthy RS, Chu FF, Geiger P, Girotti AW, Doroshow JH. Reactivity of plasma glutathione peroxidase with hydroperoxide substrates and glutathione. Arch Biochem Biophys 1993;307:29–34.PubMedCrossRefGoogle Scholar
  53. 53.
    Evans DA, Seidegard J, Narayanan N. The GSTM1 genetic polymorphism in healthy Saudi Arabians and Filipinos, and Saudi Arabians with coronary atherosclerosis. Pharmacogenetics 1996;6:365–367.PubMedCrossRefGoogle Scholar
  54. 54.
    Franceschini G, Werba JP, Safa O, Gikalov L, Sirtori CR. Dose-related increase of HDL-cholesterol after N-acetylcysteine in man. Pharmacol Res 1993;2:213–218.CrossRefGoogle Scholar
  55. 55.
    Fisher AB, Dodia C, Manevich Y, Chen JW, Feinstein SI. Phospholipid hydroperoxides are substrates for non-selenium glutathione peroxidase. J Biol Chem 1999;274:21326–21334.PubMedCrossRefGoogle Scholar
  56. 56.
    Frei B, Yamamoto Y, Niclas D, Ames BN. Evaluation of an isoluminol chemiluminescence assay for the detection of hydroperoxides in human blood plasma. Anal Biochem 1988;175:120–130.PubMedCrossRefGoogle Scholar
  57. 57.
    Georgiou I, Filiadis IF, Alamanos Y, Bouba I, Giannakopoulos X, Lolis D. Glutathione S-transferase null genotypes in transitional cell bladder cancer: A case-control study. Eur Urol 2000;37:660–666.PubMedCrossRefGoogle Scholar
  58. 58.
    Girisha KM, Gilmour A, Mastana S, Singh VP, Sinha N, Tewari S, Ramesh V, Sankar VH, Agrawal S. T1 and M1 polymorphism in glutathione S-transferase gene and coronary artery disease in North Indian population. Indian J Med Sci 2004;58:520–526.PubMedGoogle Scholar
  59. 59.
    Go YM, Jones DP. Intracellular proatherogenic events and cell adhesion modulated by extracellular thiol/disulfide redox state. Circulation 2005;111:2973–2980.PubMedCrossRefGoogle Scholar
  60. 60.
    Gokkusu C, Palanduz S, Ademoglu E, Tamer S. Oxidant and antioxidant systems in niddm patients: influence of vitamin E supplementation. Endocrine Res. 2001;27:377–386.CrossRefGoogle Scholar
  61. 61.
    Gotlieb A. Systemic and nontraditional markers of endothelial dysfunction. Can J Cardiol 2000;16(Suppl E):27E–31E.Google Scholar
  62. 62.
    Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Sales Luis AC, Parrot-Rouland FM, Tan KS, Higgins I, Garcon D, Andria G, Medrano MJ, Candito M, Evans AE, Andria G. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. J Amer Med Assoc 1997;277:1775–1781.CrossRefGoogle Scholar
  63. 63.
    Gulick AM, Fahl WE. Mammalian glutathione S-transferase: Regulation of an enzyme system to achieve chemotherapeutic efficacy. Pharmac Ther 1995;66:237–257.CrossRefGoogle Scholar
  64. 64.
    Haber F, Weiss J. The catalytic decomposition of hydrogen peroxide by iron salts. Proc R Soc Lond 1934;147:332–351.CrossRefGoogle Scholar
  65. 65.
    Haberbosch W, Jantos C. Chlamydia pneumoniae infection is not an independent risk factor for arterial disease. Herz 2000;25:79–83.PubMedCrossRefGoogle Scholar
  66. 66.
    Hapyn E, Czerwionka-Szaflarska M, Drewa G. Enzymatic efficiency of erythrocyte antioxidant barrier and lipid peroxidation in children from families with high risk of early atherosclerosis. Med Sci Monit 2001;6:112–116.Google Scholar
  67. 67.
    Hayes JD, Pulford DJ. The glutathione S-transferase supergene family: Regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 1995;30:445–600.PubMedCrossRefGoogle Scholar
  68. 68.
    Holley AE, Slater TF. Measurement of lipid hydroperoxides in normal human blood plasma using HPLC-chemiluminescence linked to a diode array detector for measuring conjugated dienes. Free Radic Res Commun 1991;15:51–63.PubMedCrossRefGoogle Scholar
  69. 69.
    Holtzman JL, Gillette JR, Milne GWA. The incorporation of 18O2 into naphthalene in the enzymatic formation of 1, 2- dihydronaphthalene-1, 2-diol. J Biol Chem 1967;242: 4386–4387.PubMedGoogle Scholar
  70. 70.
    Holtzman JL, Gillette JR, Milne GWA. The metabolic products of naphthalene in mammalian systems. J Am Chem Soc 1967;89:6341–6343.PubMedCrossRefGoogle Scholar
  71. 71.
    Holtzman JL. The role of low levels of the serum glutathione-dependet peroxidase and glutathione and high levels of serum homocysteine in the development of cardiovascualar disease. Clin Lab 2002;48:129–130.PubMedGoogle Scholar
  72. 72.
    Holvoet P, Perez G, Zhao Z, Brouwers E, Bernar H, Collen D. Malondialdehyde-modified low density lipoproteins in patients with atherosclerotic disease. J Clin Invest 1995;95: 2611–2619.PubMedCrossRefGoogle Scholar
  73. 73.
    Huerta JM, Gonzalez S, Fernandez S, Patterson AM, Lasheras C. No evidence for oxidative stress as a mechanism of action of hyperhomocysteinemia in humans. Free Radical Res 2004;38:1215–21.CrossRefGoogle Scholar
  74. 74.
    Hurst R, Bao Y, Jemth P, Mannervik B, Williamson G. Phospholipid hydroperoxide glutathione peroxidase activity of human glutathione transferases. Biochem J 1998;332: 97–100.PubMedGoogle Scholar
  75. 75.
    Imai H, Hirao F, Sakamoto T, Sekine K, Mizukura Y, Saito M, Kitamoto T, Hayasaka M, Hanaoka K, Nakagawa Y. Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene. Biochem Biophys Res Commun 2003;305:278–286.PubMedCrossRefGoogle Scholar
  76. 76.
    Inal M, Sunal E, Kanbak G, Zeytinoglu S. Effects of postmenopausal hormone replacement and alpha-tocopherol on the lipid profiles and antioxidant status. Clinica Chimica Acta 1997;268:21–9.CrossRefGoogle Scholar
  77. 77.
    Inoue H, Kiyohara C, Shinomiya S, Marugame T, Tsuji E, Handa K, Hayabuchi H, Eguchi H, Fukushima Y, Kono S. Glutathione S-transferase polymorphisms and risk of colorectal adenomas. Cancer Lett 2001;163:201–206.PubMedCrossRefGoogle Scholar
  78. 78.
    Izzotti A, De Flora S, Petrilli GL, Gallagher J, Rojas M, Alexandrov K, Bartsch H, Lewtas J. Cancer biomarkers in human atherosclerotic lesions: Detection of DNA adducts. Cancer Epidemiol Prevent 1995;4:105–110.CrossRefGoogle Scholar
  79. 79.
    Izzotti A, Cartiglia C, Lewtas J, De Flora S. Increased DNA alterations in atherosclerotic lesions of individuals lacking the GSTM1 genotype. FASEB J 2001;15:752–727.PubMedCrossRefGoogle Scholar
  80. 80.
    Jayakumari N, Ambikakumari V, Balakrishnan KG, Iyer KS. Antioxidant status in relation to free radical production during stable and unstable anginal syndromes. Atherosclerosis 1992;94:183–190.PubMedCrossRefGoogle Scholar
  81. 81.
    Jones DP, Carlson JL, Samiec PS, Sternberg P, Jr, Mody Jr VC, Reed RL, Brown LA. Glutathione measurement in human plasma. Evaluation of sample collection, storage and derivatization conditions for analysis of dansyl derivatives by HPLC. Clin Chim Acta 1998;275:175–184.Google Scholar
  82. 82.
    Joulain C, Prigent AF, Nemoz G, Lagarde M. Increased glutathione peroxidase activity in human blood mononuclear cells upon in vitro incubation with n-3 fatty acids. Biochem Pharmacol 1994;47:1315–1323.PubMedCrossRefGoogle Scholar
  83. 83.
    Kaji H, Kurasaki M, Ito K, Saito T, Saito K, Niioka T, Kojima Y, Ohsaki Y, Ide H, Tsuji M, Kondo T, Kawakami Y. Increased lipoperoxide value and glutathione peroxidase activity in blood plasma of type 2 (non-insulin-dependent) diabetic women. Klinische Wochenschrift 1985;63:765–768.PubMedCrossRefGoogle Scholar
  84. 84.
    Kashyap MK, Yadav V, Sherawat BS, Jain S, Kumari S, Khullar M, Sharma PC, Nath R. Different antioxidants status, total antioxidant power and free radicals in essential hypertension. Mole Cell Biochem 2005;277:89–99.CrossRefGoogle Scholar
  85. 85.
    Kaur G, Misra MK, Sanwal GG, Shanker K, Chandra M. Levels of glutathione reductase and glutathione peroxidase of human platelets in unstable angina and myocardial infarction. Bollettino Chimico Farmaceutico 1999;138:437–439.PubMedGoogle Scholar
  86. 86.
    Kaviarasan K, Arjunan MM, Pugalendi KV. Lipid profile, oxidant-antioxidant status and glycoprotein components in hyperlipidemic patients with/without diabetes. Clinica Chimica Acta 2005;362:49–56.CrossRefGoogle Scholar
  87. 87.
    Kihara M, Kihara M, Noda, K. Lung cancer risk of GSTM1 null genotype is dependent on the extent of tobacco smoke exposure. Carcinogenesis 1994;15:415–418.PubMedCrossRefGoogle Scholar
  88. 88.
    Kihara M, Kihara M, Noda K. Risk of smoking for squamous and small cell carcinomas of the lung modulated by combinations of CYP1A1 and GSTM1 gene polymorphisms in a Japanese population. Carcinogenesis 1995;16:2331–2336.PubMedCrossRefGoogle Scholar
  89. 89.
    Kinscherf R, Cafaltzis K, Roder F, Hildebrandt W, Edler L, Deigner HP, Breitkreutz R, Feussner, G, Kreuzer J, Werle E, Michel G, Metz J, Droge W. Cholesterol levels linked to abnormal plasma thiol concentrations and thiol/disulfide redox status in hyperlipidemic subjects. Free Rad Biol Med 2003;35:1286–1292.Google Scholar
  90. 90.
    Kobayashi S, Inoue N, Azumi H, Seno T, Hirata K, Kawashima S, Hayashi Y, Itoh H, Yokozaki H, Yokoyama M. Expressional changes of the vascular antioxidant system in atherosclerotic coronary arteries. J Atheroscler Thromb 2002;9:184–190.PubMedGoogle Scholar
  91. 91.
    Kontush A, Spranger T, Reich A, Djahansouzi S, Karten B, Braesen JH, Finckh B, Kohlschutter A, Beisiegel U. Whole plasma oxidation assay as a measure of lipoprotein oxidizability. Biofactors 1997;6:99–109.PubMedCrossRefGoogle Scholar
  92. 92.
    Konukoglu D, Akcay T, Erdem T. Susceptibility of erythrocyte lipids to oxidation and erythrocyte antioxidant status in myocardial infarction. Clin Biochem 1998;31:667–671.PubMedCrossRefGoogle Scholar
  93. 93.
    Koramaz I, Pulathan Z, Usta S, Karahan SC, Alver A, Yaris E, Kalyoncu NI, Ozcan F. Cardioprotective effect of cold-blood cardioplegia enriched with N-acetylcysteine during coronary artery bypass grafting. Ann Thorac Surg 2006;81:613–618.PubMedCrossRefGoogle Scholar
  94. 94.
    Kristal B, Shurtz-Swirski R, Chezar J, Manaster J, Levy R, Shapiro G, Weissman I, Shasha SM, Sela S. Participation of peripheral in the oxidative stress and inflammation in patients with essential hypertension. Am J Hypertension 1998;11:921–928.CrossRefGoogle Scholar
  95. 95.
    Lafuente A, Pujol F, Carretero P, Villa JP, Cuchi A. Human glutathione S-transferase m (GST m) deficiency as a marker for the susceptibility to bladder and larynx cancer among smokers. Cancer Lett 1993;68:49–54.PubMedCrossRefGoogle Scholar
  96. 96.
    Lagrand WK, Visser CA, Hermens WT, Niessen HW, Verheugt FW, Wolbink GJ, Hack CE. C-reactive protein as a cardiovascular risk factor: more than an epiphenomenon? Circulation 1999;100:96–102.PubMedGoogle Scholar
  97. 97.
    Lallas TA, McClain SK, Shahin MS, Buller RE. The glutathione S-transferase M1 genotype in ovarian cancer. Cancer Epidemiol. Biomarkers Prevent. 2000;9: 587–590.Google Scholar
  98. 98.
    Lane J.D, Opara EC, Rose JE, Behm F. Quitting smoking raises whole blood glutathione. Physiol Behav 1996;60:1379–1381.PubMedCrossRefGoogle Scholar
  99. 99.
    Lang M, Pelkonen O. Metabolism of xenobiotics and chemical carcinogenesis. Chapter 3. In: Ryder W (Ed). Metabolic Polymorphisms and Susceptibility to Cancer. IRAC Scientific Publication No. 148.Google Scholar
  100. 100.
    Lapenna D, de Gioia S, Ciofani G, Mezzetti A, Ucchino S, Calafiore AM, Napolitano AM, Di Ilio C, Cuccurullo F. Glutathione-related antioxidant defenses in human atherosclerotic plaques. Circulation 1998;97:1930–1934.PubMedGoogle Scholar
  101. 101.
    Laplaud PM, Dantoine T, Chapman MJ. Paraoxonase as a risk marker for cardiovascular disease: facts and hypotheses. Clin Chem Lab Med 1998;36:431–441.PubMedCrossRefGoogle Scholar
  102. 102.
    Lee DH, Silventoinen K, Jacobs Jr DR, Jousilahti P, Tuomileto J. 1-Glutamyltransferase, obesity, and the risk of type 2 diabetes: Observational cohort study among 20, 158 middle-aged men and women. J Clin Endocrinol Metab 2004;5410–5414.Google Scholar
  103. 103.
    Lee DH, Blomhoff R, Jacobs Jr DR. Is serum gamma glutamyltransderase a marker of oxidative stress? Free Radical Res 2004;38:535–539.CrossRefGoogle Scholar
  104. 104.
    Lemaitre D, Vericel E, Polette A, Lagarde M. Effects of fatty acids on human platelet glutathione peroxidase: possible role of oxidative stress. Biochem Pharmacol 1997;53:479–486.PubMedCrossRefGoogle Scholar
  105. 105.
    Leopold JA, Loscalzo J. Oxidative enzymopathies and vascular disease. Arterioscler Thromb Vasc Biol 2005;25:1332–1340.PubMedCrossRefGoogle Scholar
  106. 106.
    Li R, Boerwinkle E, Olshan AF, Chambless LE, Pankow JS, Tyroler HA, Bray M, Pittman GS, Bell DA, Heiss G. Glutathione S-transferase genotype as a susceptibility factor in smoking-related coronary heart disease. Atherosclerosis 2000;49:451–462.CrossRefGoogle Scholar
  107. 107.
    Li R, Folsom AR, Sharrett AR, Couper D, Bray M, Tyroler HA. Interaction of the glutathione S-transferase genes and cigarette smoking on risk of lower extremity arterial disease: the Atherosclerosis Risk in Communities (ARIC) study. Atherosclerosis 2001;154:729–738.PubMedCrossRefGoogle Scholar
  108. 108.
    Lim PS, Wei YH, Yu YL, Kho B. Enhanced oxidative stress in haemodialysis patients receiving intravenous iron therapy. Nephrol Dial Transplant 1999;14:2680–2687.PubMedCrossRefGoogle Scholar
  109. 109.
    Loeper J, Goy J, Rozensztajn L, Bedu O, Moisson P. Lipid peroxidation and protective enzymes during myocardial infarction. Clinica Chimica Acta 1991;196:119–125.CrossRefGoogle Scholar
  110. 110.
    Loeper J, Goy J, Klein JM, Dufour M, Bedu O, Loeper S, Emerit J. The evolution of oxidative stress indicators in the course of myocardial ischemia. Free Radical Res Commun 1991;2:675–680.CrossRefGoogle Scholar
  111. 111.
    London SJ, Yuan JM, Chung FL, Gao YT, Coetzee GA, Ross RK, Yu MC. Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk: A prospective study of men in Shanghai, China Lancet 2000;356:724–729.CrossRefGoogle Scholar
  112. 112.
    Maddipati KR, Marnett LJ. Characterization of the major hydroperoxide-reducing activity of human plasma. Purification and properties of a selenium-dependent glutathione peroxidase. J Biol Chem 1987;262:17398–17403.PubMedGoogle Scholar
  113. 113.
    Markovic S, Dordevic J, Majkic-Singh N, Vasiljevic Z, Petrovic M, Glavinic L, Letic S, Milosevic A. The importance of antioxidant enzyme and total antioxidant status of patients with acute myocardial infarction on thrombolytic therapy. Clin Lab 2000;46:495–499.PubMedGoogle Scholar
  114. 114.
    Maser RL, Magenheimer BS, Calvet JP. Mouse plasma glutathione peroxidase: dDna sequence analysis and renal proximal tubular expression and secretion. J Biol Chem 1994;269:27066–27073.PubMedGoogle Scholar
  115. 115.
    Matetzky S, Freimark D, Ben-Ami S, Goldenberg I, Leor J, Doolman R, Novikov I, Eldar M, Hod H. Association of elevated homocysteine levels with a higher risk of recurrent coronary events and mortality in patients with acute myocardial infarction. Arch Int Med 2003;163:1933–1942.CrossRefGoogle Scholar
  116. 116.
    Matteucci E, Giampietro O. Oxidative stress in families of type 1 diabetic patients. Diabetes Care 2000;23:1182–1106.PubMedCrossRefGoogle Scholar
  117. 117.
    McMurray J, Chopra M, Abdullah I, Smith WE, Dargie HJ. Evidence for oxidative stress in unstable angina. Br Heart J 1992;68:454–457.PubMedCrossRefGoogle Scholar
  118. 118.
    McWilliams JE, Sanderson BJS, Harris EL, Richert-Boe KE, Henner WD. Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk. Cancer Epidemol. Biomarkers Prevent 1995;4:589–584.Google Scholar
  119. 119.
    Mezzetti A, Lapenna D, Calafiore AM, Proietti-Franceschilli G, Porreca E, De Cesare D, Neri M, Di Ilio C, Cuccurullo F. Glutathione-related enzyme activities and lipoperoxide levels in human internal mammary artery and ascending aorta. Relations with serum lipids. Arteriosc Thromb 1992;12:92–98.Google Scholar
  120. 120.
    Michelet F, Gueguen R, Leroy P, Wellman M, Nicolas A, Siest G. Blood and plasma glutathione measured in healthy subjects by HPLC: Relation to sex, aging, biological variables, and life habits. Clin Chem 1995;41:1509–1517.PubMedGoogle Scholar
  121. 121.
    Mills BJ, Weiss MM, Lang CA, Liu MC, Ziegler C. Blood glutathione and cysteine changes in cardiovascular disease. J Lab Clin Med 2000;135:396–401.PubMedCrossRefGoogle Scholar
  122. 122.
    Minekura H, Kumagai T, Kawamoto Y, Nara F, Uchida K. 4-Hydroxy-2-nonenal is a powerful endogenous inhibitor of endothelial response. Biochem Biophys Res Commun 2001;282:557–561.PubMedCrossRefGoogle Scholar
  123. 123.
    Miyazawa T, Saeki R, Inaba H. Detection of chemiluminescence in lipid peroxidation of biological systems and its application to HPLC. J Biolumin Chemilumin 1990;4: 475–478.CrossRefGoogle Scholar
  124. 124.
    Miyazawa T. Determination of phospholipid hydroperoxides in human blood plasma by a chemiluminescence-HPLC assay. Free Radic Biol Med 1989;7:209–217.PubMedCrossRefGoogle Scholar
  125. 125.
    Miyazawa T, Fujimoto K, Oikawa S. Determination of lipid hydroperoxides in low density lipoprotein from human plasma using high performance liquid chromatography with chemiluminescence detection. Biomed. Chromatogr 1990;4:131–134.PubMedCrossRefGoogle Scholar
  126. 126.
    Moat SJ, Bonham JR, Cragg RA, Powers HJ. Elevated plasma homocysteine elicits an increase in antioxidant enzyme activity. Free Rad Res 2000;32:171–179.CrossRefGoogle Scholar
  127. 127.
    Moghadasian MH, McManus BM, Frohlich JJ. Homocyst(e) ine and coronary artery disease. Clinical evidence and genetic and metabolic background. Arch Intern Med 1997;157: 2299–2308.PubMedCrossRefGoogle Scholar
  128. 128.
    Molcanyiova A, Stancakova A, Javorsky M, Tkac I. Beneficial effect of simvastatin treatment on LDL oxidation and antioxidant protection is more pronounced in combined hyperlipidemia than in hypercholesterolemia. Pharmacol Res 2006;54:203–307.PubMedCrossRefGoogle Scholar
  129. 129.
    Morrison JA, Jacobsen DW, Sprecher DL, Robinson K, Khoury P, Daniels SR. Serum glutathione in adolescent males predicts parental coronary heart disease. Circulation 1999;300:2244–2247.Google Scholar
  130. 130.
    Mullenbach GT, Tabrizi A, Irvine BD, Bell GI, Hallewel RA. Sequence of a cDNA coding for human glutathione peroxidase confirms TGA encodes active site selenocysteine. Nucleic Acids Res 1987;15:5484.PubMedCrossRefGoogle Scholar
  131. 131.
    Nuttall SL, Martin U, Sinclair AJ, Kendall MJ. Glutathione: in sickness and in health. Lancet 1998;351:645–466.PubMedCrossRefGoogle Scholar
  132. 132.
    Nourooz-Zadeh J, Tajaddini-Sarmadi J, Ling K-L, Wolff SP. Low-density lipoprotein is the major carrier of lipid hydroperoxides in plasma. Relevance to determination of total plasma lipid hydroperoxide concentrations. Biochem J 1996;313:781–786.PubMedGoogle Scholar
  133. 133.
    Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997;337:230–236.PubMedCrossRefGoogle Scholar
  134. 134.
    Oen LH, Utomo H, Suyatna F, Hanafiah A, Asikin N. Plasma lipid peroxides in coronary heart disease. Int J Clin Pharmacol Ther Toxicol 1992;30:77–80.PubMedGoogle Scholar
  135. 135.
    Okkels H, Sigsgaard T, Wolf H, Autrup H. Glutathione S-transferase m as a risk factor in bladder tumours. Pharmacogenetics 1996;6:251–256.PubMedCrossRefGoogle Scholar
  136. 136.
    Olshan AF, Li R, Pankow JS, Bray M, Tyroler HA, Chambless LE, Boerwinkle E, Pittman GS, Bell DA. Risk of atherosclerosis: interaction of smoking and glutathione S-transferase genes. Epidemiology 2003;14:321–327.PubMedCrossRefGoogle Scholar
  137. 137.
    Oude Ophuis MB, van Lieshout EM, Roelofs HM, Peters WH, Manni JJ. Glutathione S-transferase M1 and T1 and Cytochrome P4501A1 polymorphisms in relation to the risk for benign and malignant head and neck lesions. Cancer 1998;82:936–943.PubMedCrossRefGoogle Scholar
  138. 138.
    Ozden S, Dildar K, Kadir YH, Gulizar K. The effects of hormone replacement therapy on lipid peroxidation and antioxidant status. Maturitas 1997;38:165–170.CrossRefGoogle Scholar
  139. 139.
    Ozden M, Maral H, Akaydin D, Cetinalp P, Kalender B. Erythrocyte glutathione peroxidase activity, plasma malondialdehyde and erythrocyte glutathione levels in hemodialysis and CAPD patients. Clin Biochem 2002;35:269–273.PubMedCrossRefGoogle Scholar
  140. 140.
    Palanduz S, Ademoglu E, Gokkusu C, Tamer S. Plasma antioxidants and type 2 diabetes mellitus. Res Commun Mol Pathol Pharmacol 2001;109:309–318.PubMedGoogle Scholar
  141. 141.
    Pandey NR, Kaur G, Chandra M, Sanwal GG, Misra MK. Enzymatic oxidant and antioxidants of human blood platelets in unstable angina and myocardial infarction. Int J Cardiol 2000;76:33–38.PubMedCrossRefGoogle Scholar
  142. 142.
    Parthasarathy S, Young SG, Witztum JL, Pittman RC, Steinberg D. Probucol inhibits oxidative modification of low density lipoprotein. J Clin Invest 1986;77:641–644.PubMedCrossRefGoogle Scholar
  143. 143.
    Parthasarathy S, Khoo JC, Miller E, Barnett J, Witztum JL, Steinberg D. Low density lipoprotein rich in oleic acid is protected against oxidative modification: implications for dietary prevention of atherosclerosis. Proc Natl Acad Sci USA 1990;87:3894–3898.PubMedCrossRefGoogle Scholar
  144. 144.
    Pasaoglu H, Sancak B, Bukan N. Lipid peroxidation and resistance to oxidation in patients with type 2 diabetes mellitus. Tohoku J Exp Med 2004;203:211–218.PubMedCrossRefGoogle Scholar
  145. 145.
    Pereira EC, Bertolami MC, Faludi AA, Sevanian A, Abdalla DS. Antioxidant effect of simvastatin is not enhanced by its association with alpha-tocopherol in hypercholesterolemic patients. Free Radical Biol Med 2004;37:1440–1448.CrossRefGoogle Scholar
  146. 146.
    Perera FP. Molecular epidemiology and prevention of cancer. Environ. Health Perspect. 1995;103(Suppl 8):233–236.Google Scholar
  147. 147.
    Pessah-Rasmussen H, Jerntorp P, Stavenow L, Elmstahl S, Hansen F, Seidegard J, Galvard H, Brattstrom L, Hampelt A. Eighty-year-old men without cardiovascular disease in the community of Malmo. Part II. Smoking characteristics and ultrasound findings with special reference to glutathione transferase and pyridoxal-5-phosphate. J Intern Med 1990;228: 17–22.Google Scholar
  148. 148.
    Pessah-Rasmussen H, Stavenow L, Seidegard J, Solem JO, Israelsson B. Lack of glutathione transferase activity in intermittent claudication. Int Angiol 1990;9:70–74.PubMedGoogle Scholar
  149. 149.
    Porter M, Pearson DJ, Suarez-Mendez VJ, Blann AD. Plasma, platelet and erythrocyte glutathione peroxidases as risk factors in ischaemic heart disease in man. Clin Sci 1992;83: 343–345.PubMedGoogle Scholar
  150. 150.
    Rangaswamy S, Penn MS, Saidel GM, Chisolm GM. Exogenous oxidized low-density lipoprotein injures and alters the barrier function of endothelium in rats in vivo. Circ Res 1997;80:37–41.PubMedGoogle Scholar
  151. 151.
    Ridker PM. Evaluating novel cardiovascular risk factors: can we better predict heart attacks?. Ann Intern Med 1999;130:933–937.PubMedGoogle Scholar
  152. 152.
    Rothman N, Hayes RB. Using biomarkers of genetic susceptibility to enhance the study of cancer etiology. Environ. Health Perspect 1995;103(Suppl 8):291–295.Google Scholar
  153. 153.
    Roxborough HE, Mercer C, McMaster D, Maxwell AP, Young IS. Plasma glutathione peroxidase activity is reduced in haemodialysis patients. Nephron 1999;81:278–283.PubMedCrossRefGoogle Scholar
  154. 154.
    Rozenberg O, Shih DM, Aviram M. Paraoxonase 1 (PON1) attenuates macrophage oxidative status: studies in PON1 transfected cells and in PON1 transgenic mice. Atherosclerosis 2005;181:9–18.PubMedCrossRefGoogle Scholar
  155. 155.
    Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med 1999;341:410–418.PubMedCrossRefGoogle Scholar
  156. 156.
    Ruiz C, Alegria A, Barbera R, Farre R, Lagarda MJ. Lipid peroxidation and antioxidant enzyme activities in patients with type 1 diabetes mellitus. Scand J Clin Lab Invest 1999;59: 99–105.PubMedCrossRefGoogle Scholar
  157. 157.
    Ruiz MC, Medina A, Moreno JM, Gomez I, Ruiz N, Bueno P, Asensio C, Osuna A. Relationship between oxidative stress parameters and atherosclerotic signs in the carotid artery of stable renal transplant patients. Transplant Proceed 2005;37:3796–3798.CrossRefGoogle Scholar
  158. 158.
    Ruttmann E, Brant LJ, Concin H, Diem G, Rapp K, Ulmer H. the Vorarlberg Health Monitoring and Promotion Program Study Group. 1-Glutamyltransferase as a risk factor for cardiovascular disease mortality; An epdiemiological investigation in a cohort of 163, 944 Austrian adults. Circulation 2005;112:130–2137.Google Scholar
  159. 159.
    Sakamaki R, Nagano S, Yamazaki S, Ozawa N, Tateishi M, Okuda H, Watabe T. Existence of 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ols in lipoproteins from diabetic patients and normal subjects. J Atheroscler Thromb 1994;1:80–86.PubMedGoogle Scholar
  160. 160.
    Salonen JT, Yla-Herttuala Yamamoto R, Butler S, Korpela H, Salonen R, Nyyssonen K, Palinski W, Witztum JL. Autoantibodies against oxidised LDL and progression of carotid atherosclerosis. Lancet 1992;339:883–887.PubMedCrossRefGoogle Scholar
  161. 161.
    Seidegard J, Pero RW. The hereditary transmission of high glutathione transferase activity towards tran-stilbene oxide in human mononuclear leukocytes from human blood. Human Genet 198569:66–68.Google Scholar
  162. 162.
    Seidegard J, Pero RW, Miller DG, Beattie EJ. A glutathione transferase in human leukocytes as a marker for the susceptibility to lung cancer. Carcinogenesis 1986;7:751–753.PubMedCrossRefGoogle Scholar
  163. 163.
    Sela S, Shurtz-Swirski R, Awad J, Shapiro G, Nasser L, Shasha SM, Kristal B. The involvement of peripheral polymorphonuclear leukocytes in the oxidative stress and inflammation among cigarette smokers. Israel Med Assoc J 2002;4:1015–1019.Google Scholar
  164. 164.
    Serdar Z, Aslan K, Dirican M, Sarandol E, Yesilbursa D, Serdar A. Lipid and protein oxidation and antioxidant status in patients with angiographically proven coronary artery disease. Clin Biochem 2006;39:794–803.PubMedCrossRefGoogle Scholar
  165. 165.
    Sevanian A, Bittolo-Bon G, Cazzolato G, Hodis H, Hwang J, Zamburlini A, Maiorino M, Ursini F. LDL- is a lipid hydroperoxide-enriched circulating lipoprotein. J Lipid Res 1997;38:419–428.PubMedGoogle Scholar
  166. 166.
    Shen L, Sevanian A. OxLDL induces macrophage gamma-GCS-HS protein expression: a role for oxLDL-associated lipid hydroperoxide in GSH synthesis. J Lipid Res 2001;42: 813–823.PubMedGoogle Scholar
  167. 167.
    Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG, Fogelman AM, Lusis AJ. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 1998;394:284–287.PubMedCrossRefGoogle Scholar
  168. 168.
    Shurtz-Swirski R, Sela S, Herskovits AT, Shasha SM, Shapiro G, Nasser L, Kristal B. Involvement of peripheral polymorphonuclear leukocytes in oxidative stress and inflammation in type 2 diabetic patients. Diabetes Care 2001;24:104–110.PubMedCrossRefGoogle Scholar
  169. 169.
    Siemianowicz K, Gminski J, Francuz T, Wojcik A, Posielezna B. Activity of antioxidant enzymes in children from families at high risk of premature coronary heart disease. Scand J Clin Lab Invest 2003;63:151–158.PubMedGoogle Scholar
  170. 170.
    Simic D, Mimic-Oka J, Pljesa M, Milanovic D, Radojevic S, Ivanovic B, Kalimanovska-Ostric D, Matic D, Simic T. Time course of erythrocyte antioxidant activity in patients treated by thrombolysis for acute myocardial infarction. Jpn Heart J 2003;44:823–832.PubMedCrossRefGoogle Scholar
  171. 171.
    Sneddon AA, Wu HC, Farquharson A, Grant I, Arthur JR, Rotondo D, Choe SN, Wahle KW. Regulation of selenoprotein GPx4 expression and activity in human endothelial cells by fatty acids, cytokines and antioxidants. Atherosclerosis 2003;171:57–65.PubMedCrossRefGoogle Scholar
  172. 172.
    Solak ZA, Kabaroglu C, Cok G, Parildar Z, Bayindir U, Ozmen D, Bayindir O. Effect of different levels of cigarette smoking on lipid peroxidation, glutathione enzymes and paraoxonase 1 activity in healthy people. Clin Exp Med 2005;5:99–105.PubMedCrossRefGoogle Scholar
  173. 173.
    Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1998;320:915–924.Google Scholar
  174. 174.
    Stickel F, Osterricher CH, Datz C, Ferinci P, Wolfel M, Norgauer W, Kraus MR, Wrba F, Hellerbrand C, Schuppan D. Prediction of progression to cirrhosis by glutahione S-transferase P1 polymorphism in subjects with hereditary hemochromatosis. Arch Int Med 2005;165:1835–1840.CrossRefGoogle Scholar
  175. 175.
    Sutken E, Inal M, Ozdemir F. Effects of vitamin E and gemfibrozil on lipid profiles, lipid peroxidation and antioxidant status in the elderly and young hyperlipidemic subjects. Saudi Med J 2006;27:453–459.PubMedGoogle Scholar
  176. 176.
    Takahashi K, Avissar N, Whitin J, Cohen H. Purification and characterization of human plasma glutathione peroxidase: a selenoglycoprotein distinct from the known cellular enzymes. Arch Biochem Biophys 1987;256:677–686.PubMedCrossRefGoogle Scholar
  177. 177.
    Takahashi K, Akasaka M, Yamamoto Y, Kobayashi C, Mizoguchi J, Koyama J. Primary structure of human plasma glutathione peroxidase deduced from cDNA sequences. J Biochem (Tokyo) 1990;108:145–148.Google Scholar
  178. 178.
    Tamer L, Sucu N, Polat G, Ercan B, Aytacoglu B, Yucebilgic G, Unlu A, Dikmengil M, Atik U. Decreased serum total antioxidant status and erythrocyte-reduced glutathione levels are associated with increased serum malondialdehyde in atherosclerotic patients. Arch Med Res 2002;33:257–260.PubMedCrossRefGoogle Scholar
  179. 179.
    Tamer L, Ercan B, Camsari A, Yildirim H, Cicek D, Sucu N, Ates NA, Atik U. Glutathione S-transferase gene polymorphism as a susceptibility factor in smoking-related coronary artery disease. Basic Res Cardiol 2004;99:223–229.PubMedCrossRefGoogle Scholar
  180. 180.
    Telci A, Cakatay U, Kayali R, Erdogan C, Orhan Y, Sivas A, Akcay T. Oxidative protein damage in plasma of type 2 diabetic patients. Hormone Metab Res 2000;32:40–43.CrossRefGoogle Scholar
  181. 181.
    Tenkanen L, Manttari M, Kpvanen PT, Virkkunen H, Manninen V. Gemfibrozil in the treatment of dyslipidemia: An 18 year follow-up of the Helsinki Heart Study. Arch Intern Med 2006;166:743–748.PubMedCrossRefGoogle Scholar
  182. 182.
    Thirman MJ, Albrecht JH, Krueger MA, Erickson RR, Cherwitz DL, Park SS, Gelboin HV, Holtzman JL. Induction of Cytochrome CYPIA1 and Formation of Toxic Metabolites of Benzo[a]pyrene by Rat Aorta: A Possible Role in Atherogenesis. Proc Natl Acad Sci USA 1994;91:5397–5401.PubMedCrossRefGoogle Scholar
  183. 183.
    Tkac I, Molcanyiova A, Javorsky M, Kozarova M. Fenofibrate treatment reduces circulating conjugated diene level and increases glutathione peroxidase activity. Pharmacol Res 2006;53:261–264.PubMedCrossRefGoogle Scholar
  184. 184.
    United Kingdom Prospective Diabetes Study United Kingdom Prospective Diabetes Study (UKPDS) 13: relative efficacy of randomly allocated diet, sulfonylurea, insulin or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. Brit Med J 1995;310:83–88.Google Scholar
  185. 185.
    Ursini F, Maiorino M, Valente M, Ferri L, Gregolin C. Purification from pig liver of a protein which protects liposomes and biomembranes from peroxidative degradation and exhibits glutathione peroxidase activity on phosphatidylcholine hydroperoxides. Biochim Biophys Acta 1982;710:197–211.PubMedGoogle Scholar
  186. 186.
    van Schooten FJ, Hirvonen A, Maas LM, de Mol BA, Kleinjan JCS, Bell DA, Durrer JD, Putative susceptibility markers of coronary artery disease: association between VDR genotype, smoking and aromatic DNA adduct levels in human right artial tissue. FASEB J 1998;12:1409–1417.PubMedGoogle Scholar
  187. 187.
    Valentine RJ, Kaplan HS, Green R, Jacobsen DW, Myers SI, Clagett GP. Lipoprotein (a), homocysteine, and hypercoagulable states in young men with premature peripheral atherosclerosis: a prospective, controlled analysis. J Vasc Surg 1996;23:53–61.PubMedCrossRefGoogle Scholar
  188. 188.
    Van Remmen H, Qi W, Sabia M, Freeman G, Estlack L, Yang H, Guo ZM, Huano TT, Strong R, Lee S, Epstein CJ, Richardson A. Multiple deficiencies in antioxidant enzymes in mice result in a compound increase in sensitivity to oxidative stress. Free Rad Biol Med 2004;36:1625–1634.PubMedCrossRefGoogle Scholar
  189. 189.
    Vericel E, Rey C, Calzada C, Haond P, Chapuy PH, Lagarde M. Age-related changes in arachidonic acid peroxidation and glutathione-peroxidase activity in human platelets. Prostaglandins 1992;43:75–85.PubMedCrossRefGoogle Scholar
  190. 190.
    Vento AE, Nemlander A, Aittomaki J, Salo J, Karhunen J, Ramo OJ. N-acetylcysteine as an additive to crystalloid cardioplegia increased oxidative stress capacity in CABG patients. Scand. Cardiovascular J 2003;37:349–355.CrossRefGoogle Scholar
  191. 191.
    Verhoef P, Hennekens CH, Malinow MR, Kok FJ, Willett WC, Stampfer MJ. A prospective study of plasma homocyst(e) ine and risk of ischemic stroke. Stroke 1994;25: 1924–1930.PubMedGoogle Scholar
  192. 192.
    Voetsch B, Jin RC, Bierl C, Benke KS, Kenet G, Simioni P, Ottaviano F, Damasceno BP, Annichino-Bizacchi JM, Handy DE, Loscalzo J. Promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene: a novel risk factor for arterial ischemic stroke among young adults and children. Stroke 2007;38:41–49.PubMedCrossRefGoogle Scholar
  193. 193.
    Voutilainen S, Morrow JD, Roberts 2nd LJ, Alfthan G, Alho H, Nyyssonen K, Salonen JT. Enhanced in vivo lipid peroxidation at elevated plasma total homocysteine levels. Arterioscler Thromb Vasc Biol 1999;19:1263–1266.PubMedGoogle Scholar
  194. 194.
    Wang XL, Greco M, Sim AS, Duarte N, Wang J, Wilcken DE. Glutathione S-transferase mu1 deficiency, cigarette smoking and coronary artery disease. J Cardiovasc Risk 2002;9: 25–31.PubMedCrossRefGoogle Scholar
  195. 195.
    Watson AD, Leitinger N, Navab M, Faull KF, Horkko S, Witztum JL, Palinski W, Schwenke D, Salomon RG, Sha W, Subbanagounder G, Fogelman AM, Berliner JA. Structural identification by mass spectrometry of oxidized phospholipids in minimally oxidzed low density lipoprotein that induce monocyte/endothelial interactions and evidence for their presence in vivo. J Biol Chem 1997;272:13597–13607.PubMedCrossRefGoogle Scholar
  196. 196.
    Wendel A, Cikryt P. The level and half-life of glutathione in human sera. FEBS Lett 1980;120:209–211.PubMedCrossRefGoogle Scholar
  197. 197.
    Willerson JT. Systemic and local inflammation in patients with unstable atherosclerotic plaques. Prog Cardiovasc Dis 2002;44:469–78.PubMedCrossRefGoogle Scholar
  198. 198.
    Wilson MH, Grant PJ, Hardie LJ, Wild CP. Glutathione S-transferase M1 null genotype is associated with a decreased risk of myocardial infarction. FASEB J 2000;14:791–796.PubMedGoogle Scholar
  199. 199.
    Wilson MH, Grant PJ, Kain K, Warner DP, Wild CP. Association between the risk of coronary artery disease in South Asians and a deletion polymorphism in glutathione S-transferase M1. Biomarkers 2003;8:43–50.PubMedCrossRefGoogle Scholar
  200. 200.
    Winter JP, Gong Y, Grant PJ, Wild CP. Glutathione peroxidase 1 genotype is associated with an increased risk of coronary artery disease. Coron Artery Dis 2003;14:149–153.PubMedCrossRefGoogle Scholar
  201. 201.
    Women’s Health Initiative Writing Group. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321–333.CrossRefGoogle Scholar
  202. 202.
    Yagi K, Komura S, Kojima H, Sun Q, Nagata N, Ohishi N, Nishikimi M. Expression of human phospholipid hydroperoxide glutathione peroxidase gene for protection of host cells from lipid hydroperoxide-mediated injury. Biochem Biophys Res Commun 1996;219: 486–491.PubMedCrossRefGoogle Scholar
  203. 203.
    Yamamoto Y, Brodsky MH, Baker JC, Ames BN. Detection and characterization of lipid hydroperoxides at picomole levels by high-performance liquid chromatography. Anal Biochem 1987;160:7–13.PubMedCrossRefGoogle Scholar
  204. 204.
    Yamamoto Y, Takahashi K. Glutathione peroxidase isolated from plasma reduces phospholipid hydroperoxides. Arch Biochem Biophys 1993;305:541–545.PubMedCrossRefGoogle Scholar
  205. 205.
    Yaqoob M, Patrick AW, McClelland P, Stevenson A, Mason H, White MC, Bell GM. Relationship between markers of endothelial dysfunction, oxidant injury and tubular damage in patients with insulin-dependent diabetes mellitus. Clin Sci 1993;85:557–562.PubMedGoogle Scholar
  206. 206.
    Yasuda M, Narita S. Simultaneous determination of phospholipid hydroperoxides and cholesteryl ester hydroperoxides in human plasma by high-performance liquid chromatography with chemiluminescence detection. J Chromatogr B Biomed Appl 1997;693: 211–217.CrossRefGoogle Scholar
  207. 207.
    Yegin A, Yegin H, Aliciguzel Y, Deger N, Semiz E. Erythrocyte selenium-glutathione peroxidase activity is lower in patients with coronary atherosclerosis. Jap Hrt J 1997;38: 793–798.Google Scholar
  208. 208.
    Yilmaz MI, Baykal Y, Kilic M, Sonmez A, Bulucu F, Aydin A, Sayal A, Hakki Kocar IH. Effects of statins on oxidative stress. Biol Trace Element Res 2004;98:119–127.CrossRefGoogle Scholar
  209. 209.
    Yla-Herttuala S, Palinski W, Rosenfeld ME, Parthasarathy S, Carew TE, Butler S, Witztum JL, Steinberg D. Evidence of the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J Clin Invest 1989;84:1086–1095.PubMedCrossRefGoogle Scholar
  210. 210.
    Yoshida H, Sasaki K, Hirowatari Y, Kurosawa H, Sato N, Furutani N, Tada N. Increased serum iron may contribute to enhanced oxidation of low-density lipoprotein in smokers in part through changes in lipoxygenase and catalase. Clinica Chimica Acta 2004;345:161–170.CrossRefGoogle Scholar
  211. 211.
    Zamburlini A, Maiorino M, Barbera P, Roveri A, Ursini F. Direct measurement by single photon counting of lipid hydroperoxides in human plasma and lipoproteins. Anal Biochem 1995;232:107–113.PubMedCrossRefGoogle Scholar
  212. 212.
    Zebrack JS, Anderson JL. The role of inflammation and infection in the pathogenesis and evolution of coronary artery disease. Curr Cardiol Rep 2002;4:278–288.PubMedCrossRefGoogle Scholar
  213. 213.
    Zaltzberg H, Kanter Y, Aviram M, Levy Y. Increased plasma oxidizability and decreased erythrocyte and plasma antioxidative capacity in patients with NIDDM. Israel Med Assoc J 1999;1:228–231.Google Scholar
  214. 214.
    Zitouni K, Nourooz-Zadeh J, Harry D, Kerry SM, Betteridge DJ, Cappuccio FP, Earle KA. Race-specific differences in antioxidant enzyme activity in patients with type 2 diabetes: a potential association with the risk of developing nephropathy. Diabetes Care 2005;28: 1698–1703.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Jordan L. Holtzman
    • 1
  1. 1.Division of Environmental Health SciencesUniversity of MinnesotaMinneapolisUSA

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