nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное обществоnid-1987Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESРоль оксидативного стресса в патологии сердечно-сосудистой системы у больных с заболеваниями почек (Сообщение I. Патофизиология оксидативного стресса)The impact of oxidative stress on cardiovascular pathology in patients with kidney diseases (Part I. Pathophisiology of Oxidative Stress)СаенкоЮ. В.SaenkoYu. V.noemail@neicon.ruШутовА. М.ShutovA. M.amshu@mail.ruКафедра экспериментально-клинической фармакологии и биохимии и кафедра терапии и профессиональных болезней Ульяновского государственного университета, г. УльяновскRussian Federation200427062025614753Copyright © Саенко Ю.В., Шутов А.М., 20252025Саенко Ю.В., Шутов А.М.Saenko Y.V., Shutov A.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/1987

Оксидативный стресс является составной частью патогенеза многих заболеваний. Причиной возникновения окислительного стресса является увеличение продукции свободных радикалов и (или) снижение эффективности антиоксидантных систем организма. В обзоре рассмотрены основные типы свободно-радикальных молекул и радикальных реакций. Освещены основные источники возникновения свободно-радикальных молекул в клетках и представлены механизмы свободно-радикального повреждения клеток и тканей. Особое внимание уделено внеклеточным и внутриклеточным физиологическим антиоксидантным системам. Дана характеристика основных типов антиоксидантных молекул и ферментов, а также их роли в поддержании внутриклеточного окислительно-восстановительного потенциала. Первое сообщение касается патофизиологии оксидативного стресса, второе будет посвящено клиническим аспектам проблемы.

Oxidative stress is a disturbance of the balance between oxidants and anti-oxidant system. Oxidative stress accompanies many renal diseases. Here we review recent data about toxic oxygen radicals and related compounds. Oxygen radicals can modify macromolecules such as lipids, proteins and nucleic acids inducing damage of cells and tissues. Cell anti-oxidant system is reviewed. Pathological mechanisms of oxidative stress as well as clinical aspects of the problem are discussed.

заболевания почекоксидативный стресссердечно-сосудистая патологияхроническая почечная недостаточностьReferencesРозанцев Э.Г., Шолле В.Д. Органическая химия свободных радикалов. М., 1979.Розанцев Э.Г., Шолле В.Д. Органическая химия свободных радикалов. М., 1979.Семенов Н.Н. Цепные реакции. М., 1986.Семенов Н.Н. Цепные реакции. М., 1986.Эммануэль Н.М. Цепные реакции окисления углеводородов в жидкой фазе. М., 1965.Эммануэль Н.М. Цепные реакции окисления углеводородов в жидкой фазе. М., 1965.Abe M.K., Chao T.S., Solway J. et al. Hydrogen peroxide stimulates mitogen-activated protein kinase in bovine tracheal myocytes: implications for human airway disease. Am J Respir Cell Mol Biol 1994; 11: 577-585.Abe M.K., Chao T.S., Solway J. et al. Hydrogen peroxide stimulates mitogen-activated protein kinase in bovine tracheal myocytes: implications for human airway disease. Am J Respir Cell Mol Biol 1994; 11: 577-585.Allen R.G., Tresini M. Oxidative stress and gene regulation. Free Rad Biol Med 2000; 28: 463-499.Allen R.G., Tresini M. Oxidative stress and gene regulation. Free Rad Biol Med 2000; 28: 463-499.Arai N., Imai M., Koumura H. et al. Mitochondrial phospholipid hydroperoxide glutathione peroxidase plays a major role in preventing oxidative injury to cells. J Biol Chem 1999; 274: 4924-4933.Arai N., Imai M., Koumura H. et al. Mitochondrial phospholipid hydroperoxide glutathione peroxidase plays a major role in preventing oxidative injury to cells. J Biol Chem 1999; 274: 4924-4933.Arteel G.E., Briviba K., Sies H. Protection against peroxinitrite. FEBS Letters 1999; 445: 226-230.Arteel G.E., Briviba K., Sies H. Protection against peroxinitrite. FEBS Letters 1999; 445: 226-230.Awasthi Y.C., Zimniak P., Singhal S.S., Awasthi S. Physiological role of glutathione S-transferases in protection mechanisms against lipid peroxidation: A commentary. Biochem Arch 1995; 11: 47-54.Awasthi Y.C., Zimniak P., Singhal S.S., Awasthi S. Physiological role of glutathione S-transferases in protection mechanisms against lipid peroxidation: A commentary. Biochem Arch 1995; 11: 47-54.Babibor B.M. NADPH oxidase: An update. Blood 1999; 93: 1464-1476.Babibor B.M. NADPH oxidase: An update. Blood 1999; 93: 1464-1476.Beckman K.B., Ames B.N. Oxidative decay of DNA. J Biol Chem 1997; 272: 19633-19636.Beckman K.B., Ames B.N. Oxidative decay of DNA. J Biol Chem 1997; 272: 19633-19636.Beckman K.B., Ames B.N. The free radical theory of aging matures. Phys Rev 1998; 78: 548-581.Beckman K.B., Ames B.N. The free radical theory of aging matures. Phys Rev 1998; 78: 548-581.Berlett B.S., Stadtman E.R. Protein oxidation in aging, desease, and oxidative stress. J Biol Chem 1997; 272: 20313-20316.Berlett B.S., Stadtman E.R. Protein oxidation in aging, desease, and oxidative stress. J Biol Chem 1997; 272: 20313-20316.Bourdon E., Blache D. The importance of proteins in defense against oxidation. Antioxid Redox Signal 2001; 3: 293-311.Bourdon E., Blache D. The importance of proteins in defense against oxidation. Antioxid Redox Signal 2001; 3: 293-311.Brigelius-Flohe R., Traber M.G. Vitamin E: function and metabolism. FASEB J 1999; 13: 1145-1155.Brigelius-Flohe R., Traber M.G. Vitamin E: function and metabolism. FASEB J 1999; 13: 1145-1155.Cai H., Harrison D.G. Endothelial disfunction in cardiovascular diseases. The role of oxidant stress. Circ Res 2000; 87: 840-844.Cai H., Harrison D.G. Endothelial disfunction in cardiovascular diseases. The role of oxidant stress. Circ Res 2000; 87: 840-844.Candel N.S., Schumacker P.T. Cellular oxygen sensing by mitochondria: old questions, new insight. J Appl Physiol 2000; 88: 1880-1889.Candel N.S., Schumacker P.T. Cellular oxygen sensing by mitochondria: old questions, new insight. J Appl Physiol 2000; 88: 1880-1889.Carr C.A., Zhu B.-Z., Frei B. Potential antiatherogenic mechanisms of ascorbate (vitamin C) and á-tocopherol (vitamin E). Circ Res 2000; 87: 349-354.Carr C.A., Zhu B.-Z., Frei B. Potential antiatherogenic mechanisms of ascorbate (vitamin C) and á-tocopherol (vitamin E). Circ Res 2000; 87: 349-354.Crane F.L. Biochemical functions of Coenzyme Q10. J Am Coll Nutr 2001; 20: 591-598.Crane F.L. Biochemical functions of Coenzyme Q10. J Am Coll Nutr 2001; 20: 591-598.Croteau D.L., Bohr V. Repair of oxidative damage to nuclear and mitochondrial DNA in mammalian cells. J Biol Chem 1997; 272: 25409-25412.Croteau D.L., Bohr V. Repair of oxidative damage to nuclear and mitochondrial DNA in mammalian cells. J Biol Chem 1997; 272: 25409-25412.Davis K.L., Martin E., Turko I.V., Murad F. Novel effects of nitric oxide. Annu Rev Pharmacol Toxicol 2001; 41: 203-236.Davis K.L., Martin E., Turko I.V., Murad F. Novel effects of nitric oxide. Annu Rev Pharmacol Toxicol 2001; 41: 203-236.Droge W. Free radicals in the physiological control of cell function. Physiol Rev 2002; 82: 47-95.Droge W. Free radicals in the physiological control of cell function. Physiol Rev 2002; 82: 47-95.Frey B., Haupt R., Alms S. et al. Increase in fragmented phosphatidylcholine in blood plasma by oxidative stress. J Lipid Res 2000; 41: 1145-1153.Frey B., Haupt R., Alms S. et al. Increase in fragmented phosphatidylcholine in blood plasma by oxidative stress. J Lipid Res 2000; 41: 1145-1153.Fridovich I. Superoxide anion radical (O.2-), superoxide dismutases, and related matters. J Biol Chem 1997; 272: 18515-18517.Fridovich I. Superoxide anion radical (O.2-), superoxide dismutases, and related matters. J Biol Chem 1997; 272: 18515-18517.Fridovich I. Superoxide radical and superoxide dismutases. Annu Rev Biochem 1995; 64: 97-112.Fridovich I. Superoxide radical and superoxide dismutases. Annu Rev Biochem 1995; 64: 97-112.Girotti A.W. Lipid hydroperoxide generation, turnover, and effectors action in biological systems. J Lipid Res 1998; 39: 1529-1542.Girotti A.W. Lipid hydroperoxide generation, turnover, and effectors action in biological systems. J Lipid Res 1998; 39: 1529-1542.Griendling K.K., Sorescu D., Lassegue B., Usio-Fukai M. Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler. Thromb Vasc Biol 2000; 20: 2175-2183.Griendling K.K., Sorescu D., Lassegue B., Usio-Fukai M. Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler. Thromb Vasc Biol 2000; 20: 2175-2183.Griendling K.K., Sorescu D., Ushio-Fukai M. NAD(P)H oxidase. Role in cardiovascular biology and disease. Circ Res 2000; 86: 494-501.Griendling K.K., Sorescu D., Ushio-Fukai M. NAD(P)H oxidase. Role in cardiovascular biology and disease. Circ Res 2000; 86: 494-501.Halliwell B. Antioxidant defence mechanisms: from the beginning to the end (of the beginning). Free Radic Res 1999; 1: 261-272.Halliwell B. Antioxidant defence mechanisms: from the beginning to the end (of the beginning). Free Radic Res 1999; 1: 261-272.Halliwell B., Gutteridge J.M. The antioxidants of human extracellular fluids. Arch Biochem Biophys 1990; 280: 1-8.Halliwell B., Gutteridge J.M. The antioxidants of human extracellular fluids. Arch Biochem Biophys 1990; 280: 1-8.Hoidal J.R. Reactive oxygen species and cell signaling. Am J Respir Cell Mol Biol 2001; 25: 661-663.Hoidal J.R. Reactive oxygen species and cell signaling. Am J Respir Cell Mol Biol 2001; 25: 661-663.Hoimgren A. Thioredoxin and Glutaredoxin Systems. J Biol Chem 1989; 264: 13963-13966.Hoimgren A. Thioredoxin and Glutaredoxin Systems. J Biol Chem 1989; 264: 13963-13966.Irani K. Oxidant signaling in vascular cell growth, death, and survival. Circ Res 2000; 87: 179-183.Irani K. Oxidant signaling in vascular cell growth, death, and survival. Circ Res 2000; 87: 179-183.Jones D.P., Mody V.C., Carlson J.L. et al. Redox analysis of human plasma allows separation of pro-oxidant events of again from decline in antioxidant defenses. Free Rad Biol Med 2002; 33: 1290-1300.Jones D.P., Mody V.C., Carlson J.L. et al. Redox analysis of human plasma allows separation of pro-oxidant events of again from decline in antioxidant defenses. Free Rad Biol Med 2002; 33: 1290-1300.Kavanagh R.J., Kam P.C.A. Lazaroids: efficacy and mechanism of action of the 21-aminosteroids in neuroprotection. Br J Anaesth 2001; 86: 110-119.Kavanagh R.J., Kam P.C.A. Lazaroids: efficacy and mechanism of action of the 21-aminosteroids in neuroprotection. Br J Anaesth 2001; 86: 110-119.Klatt P., Lamas S. Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. Eur J Biochem 2000; 267: 4928-4944.Klatt P., Lamas S. Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. Eur J Biochem 2000; 267: 4928-4944.Klotz L.-O. Oxidant-induced signaling: Effects of peroxynitrite and singlet oxygen. Biol Chem 2002; 383: 443-456.Klotz L.-O. Oxidant-induced signaling: Effects of peroxynitrite and singlet oxygen. Biol Chem 2002; 383: 443-456.Koken T., Serteser M., Kahraman A., Gokce C. Oxidative stress markers in hepatitis C infected hemodialysis patients. J Nephrol 2002; 15: 302-307.Koken T., Serteser M., Kahraman A., Gokce C. Oxidative stress markers in hepatitis C infected hemodialysis patients. J Nephrol 2002; 15: 302-307.Kontos H.A., Wei E.P., Ellis E.F. et al. Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats. Circ Res 1985; 57: 142-150.Kontos H.A., Wei E.P., Ellis E.F. et al. Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats. Circ Res 1985; 57: 142-150.Koshi J.K. (ed). Free radicals. NY, 1980Koshi J.K. (ed). Free radicals. NY, 1980Kourie J.I. Interaction of reactive oxygen species with ion transport mechanisms. Am J Physiol 1998; 275: C1-C24.Kourie J.I. Interaction of reactive oxygen species with ion transport mechanisms. Am J Physiol 1998; 275: C1-C24.Kramer J.H., Dickens B.F., Weglicki W.B. Phospholipid hydroperoxides are precursors of lipid alkoxyl radicals produced from anoxia/reoxygenated endothelial cells. J Mol Cell Cardiol 1995; 27: 371-381.Kramer J.H., Dickens B.F., Weglicki W.B. Phospholipid hydroperoxides are precursors of lipid alkoxyl radicals produced from anoxia/reoxygenated endothelial cells. J Mol Cell Cardiol 1995; 27: 371-381.Kuhn H. Biosynthesis, metabolization and biological importance of the primary 15-lipoxygenase matabolites 15-hydro(pero)xy-5Z,8Z,11Z,13E-eicosatetraenoic acid and 13-hydro(pero)xy-9Z,11E-octadecadienoic acid. Prog Lipid Res 1997; 35: 203-206.Kuhn H. Biosynthesis, metabolization and biological importance of the primary 15-lipoxygenase matabolites 15-hydro(pero)xy-5Z,8Z,11Z,13E-eicosatetraenoic acid and 13-hydro(pero)xy-9Z,11E-octadecadienoic acid. Prog Lipid Res 1997; 35: 203-206.Kunsch C., Medford R.M. Oxidative Stress as a Regulator of Gene Expression in the Vasculature. Circ Res 1999; 85: 753-766.Kunsch C., Medford R.M. Oxidative Stress as a Regulator of Gene Expression in the Vasculature. Circ Res 1999; 85: 753-766.Manna S.K., Zhang H.J., Yan T. Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappa â and activated protein-1. J Biol Chem 1998; 273: 13245-13254.Manna S.K., Zhang H.J., Yan T. Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappa â and activated protein-1. J Biol Chem 1998; 273: 13245-13254.Mashima R., Yamamoto Y., Yoshimura S. Reduction of phosphatidylcholine hydroperoxide by apolipoprotein A-I: purification of the hydroperoxidereducing proteins from human blood plasma. J Lipid Res 1998; 39: 1133-1140.Mashima R., Yamamoto Y., Yoshimura S. Reduction of phosphatidylcholine hydroperoxide by apolipoprotein A-I: purification of the hydroperoxidereducing proteins from human blood plasma. J Lipid Res 1998; 39: 1133-1140.Mates J.M., Perez-Gomez C., Nunez de Castro I. Antioxidant enzymes and human diseases. Clin Biochem 1999; 32: 595-603.Mates J.M., Perez-Gomez C., Nunez de Castro I. Antioxidant enzymes and human diseases. Clin Biochem 1999; 32: 595-603.May J.M. Is ascorbic acid an antioxidant for the plasma membrane. FASEB J 1999; 13: 995-1006.May J.M. Is ascorbic acid an antioxidant for the plasma membrane. FASEB J 1999; 13: 995-1006.May M.J., Cobb C.E., Mendiratta S. et al. Reduction of the Ascorbyl free radical to ascorbate by thioredoxin reductase. J Biol Chem 1998; 273: 22039-23045.May M.J., Cobb C.E., Mendiratta S. et al. Reduction of the Ascorbyl free radical to ascorbate by thioredoxin reductase. J Biol Chem 1998; 273: 22039-23045.Mayer M. Association of serum bilirubin concentration with risk of coronary artery disease. Clin Chem 2000; 46: 1723-1727.Mayer M. Association of serum bilirubin concentration with risk of coronary artery disease. Clin Chem 2000; 46: 1723-1727.Mc Hugh J., Cheek D.J. Nitric oxide and regulation of vascular tone: pharmacological and physiological considerations. Am J Critical Care 1998; 7: 131-140.Mc Hugh J., Cheek D.J. Nitric oxide and regulation of vascular tone: pharmacological and physiological considerations. Am J Critical Care 1998; 7: 131-140.Meister A. Glutathione-ascorbic acid antioxidant system in animals. J Biol Chem 1994; 269: 9397-9400.Meister A. Glutathione-ascorbic acid antioxidant system in animals. J Biol Chem 1994; 269: 9397-9400.Meister A. Glutatione, ascorbat, and cellular protection. Cancer Res 1994; 54: 1969-1975.Meister A. Glutatione, ascorbat, and cellular protection. Cancer Res 1994; 54: 1969-1975.Mizuto O., Yoshimitsu K., Tomohiko A. et al. Oxidative stress by tumor-derived macrophages suppresses the expression of CD3 chain of T-cell receptor complex and antigen-specific T-cell responses. Proc Natl Acad Sci USA 1996; 93: 13119-13124.Mizuto O., Yoshimitsu K., Tomohiko A. et al. Oxidative stress by tumor-derived macrophages suppresses the expression of CD3 chain of T-cell receptor complex and antigen-specific T-cell responses. Proc Natl Acad Sci USA 1996; 93: 13119-13124.Mooradian A.D. Antioxidant properties of steroid. J Steroid Biochem Mol Biol 1993; 45: 509-511.Mooradian A.D. Antioxidant properties of steroid. J Steroid Biochem Mol Biol 1993; 45: 509-511.Moosman B., Behl C. Cytoprotective antioxidant function of tyrosine and tryptophan residues in transmembrane proteins. Eur J Biochem 2000; 267: 5687-5692.Moosman B., Behl C. Cytoprotective antioxidant function of tyrosine and tryptophan residues in transmembrane proteins. Eur J Biochem 2000; 267: 5687-5692.Morehouse K.M., Mason R.P. The transition metal-mediated formation of the hydroxyl free radical during the reduction of molecular oxygen by ferredoxin-ferredoxin: NADP+Oxidoreductase. J Biol Chem 1988; 263: 1204-1211.Morehouse K.M., Mason R.P. The transition metal-mediated formation of the hydroxyl free radical during the reduction of molecular oxygen by ferredoxin-ferredoxin: NADP+Oxidoreductase. J Biol Chem 1988; 263: 1204-1211.Neuzil J., Stocker R. Free and albumin-bound bilirubin are efficient co-antioxidants for á-Tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. J Biol Chem 1994; 269: 16712-16719.Neuzil J., Stocker R. Free and albumin-bound bilirubin are efficient co-antioxidants for á-Tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. J Biol Chem 1994; 269: 16712-16719.Nielsen F., Mikkelsen B.B., Nielsen J.B. et al. Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem 1997; 43: 1209-1214.Nielsen F., Mikkelsen B.B., Nielsen J.B. et al. Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem 1997; 43: 1209-1214.Paolicchi A., Dominichi S., Pompella A. Glutathione catabolism as a signaling mechanism. Biochem Pharmacol 2002; 64 (5-6): 1027-1035.Paolicchi A., Dominichi S., Pompella A. Glutathione catabolism as a signaling mechanism. Biochem Pharmacol 2002; 64 (5-6): 1027-1035.Pinchuk I., Schnitzer E., Lichtenberg D. Kinetic analysis of copper-induced peroxidation of LDL. Biochim Biophys Acta 1998; 1389: 155-172.Pinchuk I., Schnitzer E., Lichtenberg D. Kinetic analysis of copper-induced peroxidation of LDL. Biochim Biophys Acta 1998; 1389: 155-172.Pou S., Pou W.S., Bredt D.S. et al. Generation of superoxide by purified brain nitric oxide synthase. J Biol Chem 1992; 267: 24173-24176.Pou S., Pou W.S., Bredt D.S. et al. Generation of superoxide by purified brain nitric oxide synthase. J Biol Chem 1992; 267: 24173-24176.Practico D., Barry O.P., Lawson J.A. et al. IPF2a-I: An index of lipid peroxidation in humans. Proc Natl Acad Sci USA 1998; 95: 3449-3454.Practico D., Barry O.P., Lawson J.A. et al. IPF2a-I: An index of lipid peroxidation in humans. Proc Natl Acad Sci USA 1998; 95: 3449-3454.Rauchova H., Drahota Z., Lenaz G. Function of Coenzyme Q in the cell: Some biochemical and physiological properties. Physiol Res 1995; 44: 209-216.Rauchova H., Drahota Z., Lenaz G. Function of Coenzyme Q in the cell: Some biochemical and physiological properties. Physiol Res 1995; 44: 209-216.Reiter R.J. Melatonin: Lowering the High Price of Free Radicals. News Physiol Sci 2000; 15: 246-250.Reiter R.J. Melatonin: Lowering the High Price of Free Radicals. News Physiol Sci 2000; 15: 246-250.Rice-Evance C.A., Diplock A.T., Symons M.C.R. Thechniques in free radical research. Elsevier, Amsterdam, 1991.Rice-Evance C.A., Diplock A.T., Symons M.C.R. Thechniques in free radical research. Elsevier, Amsterdam, 1991.Salonen J.T., Nyyssonen K., Salonen R. et al. Lipoprotein oxidation and progression of carotid atherosclerosis. Circulation 1997; 95: 840-845.Salonen J.T., Nyyssonen K., Salonen R. et al. Lipoprotein oxidation and progression of carotid atherosclerosis. Circulation 1997; 95: 840-845.Sanders S.A., Eisenthal R., Harrison R. NADH oxidase activity of human xanthine oxidoreductase - generation of superoxide anion. Eur J Biochem 1997; 245: 541-548.Sanders S.A., Eisenthal R., Harrison R. NADH oxidase activity of human xanthine oxidoreductase - generation of superoxide anion. Eur J Biochem 1997; 245: 541-548.Schachinger V., Zeiher A.M. Atherogenesis - recent insights into basic mechanisms and their clinical impact. Nephrol Dial Transplant 2002; 17: 2055-2064.Schachinger V., Zeiher A.M. Atherogenesis - recent insights into basic mechanisms and their clinical impact. Nephrol Dial Transplant 2002; 17: 2055-2064.Schafer F.Q., Buettner R.G. Redox environment of the cell as viewed through the redox state of the glutathion disulfide/glutathione couple. Free Radic Biol Med 2001; 30: 1191-1212.Schafer F.Q., Buettner R.G. Redox environment of the cell as viewed through the redox state of the glutathion disulfide/glutathione couple. Free Radic Biol Med 2001; 30: 1191-1212.Taylor R.W. Mechanical deformation of the arterial wall in hypertension: A mechanism for vascular pathology. Am J Med Sci 1998; 316: 156-161.Taylor R.W. Mechanical deformation of the arterial wall in hypertension: A mechanism for vascular pathology. Am J Med Sci 1998; 316: 156-161.Teixeira H.D., Schumacher R.I., Meneghini R. Lower intracellular hydrogen peroxide levels in cells overexpressing CuZn-superoxide dismutase. Proc Natl Acad Sci 1998; 95: 7872-7875.Teixeira H.D., Schumacher R.I., Meneghini R. Lower intracellular hydrogen peroxide levels in cells overexpressing CuZn-superoxide dismutase. Proc Natl Acad Sci 1998; 95: 7872-7875.Thannickal V.J., Fanburg B.L. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 2000; 279: L1005-L1028.Thannickal V.J., Fanburg B.L. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 2000; 279: L1005-L1028.United States Renal Data System. USRDS Annual Data Report. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. 1999.United States Renal Data System. USRDS Annual Data Report. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. 1999.Vanden Hoek T.L., Becker L.B., Shao Z. et al. Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes. J Biol Chem 1998; 272: 18092-18098.Vanden Hoek T.L., Becker L.B., Shao Z. et al. Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes. J Biol Chem 1998; 272: 18092-18098.White C.R., Brock T.A., Chang L.-Y. et al. Superoxide and peroxynitrite in atherosclerosis. Proc Natl Acad Sci USA 1994; 91: 1044-1048.White C.R., Brock T.A., Chang L.-Y. et al. Superoxide and peroxynitrite in atherosclerosis. Proc Natl Acad Sci USA 1994; 91: 1044-1048.Wolfler A., Abujia P.M., Schauenstein K., Liebmann P.M. N-acetylserotonin is a better extra- and intracellular antioxidant than melatonin. FEBS Letters 1999; 449: 206-210.Wolfler A., Abujia P.M., Schauenstein K., Liebmann P.M. N-acetylserotonin is a better extra- and intracellular antioxidant than melatonin. FEBS Letters 1999; 449: 206-210.Wolin M.S. Interactions of oxidants with vascular signaling systems. Arterioscler Thromb Vasc Biol 2000; 20: 1430-1442.Wolin M.S. Interactions of oxidants with vascular signaling systems. Arterioscler Thromb Vasc Biol 2000; 20: 1430-1442.Yang Y., Cheng J.-Z., Singhal S.S. et al. Role of glutathione S-transferases in protection against lipid peroxidation. J Biol Chem 2001; 276: 19220-19230.Yang Y., Cheng J.-Z., Singhal S.S. et al. Role of glutathione S-transferases in protection against lipid peroxidation. J Biol Chem 2001; 276: 19220-19230.Zhao Y., Wang Z.B., Xu J.-X. Effect of cytochrome c on the generation and elimination of O2* and H2O2 in mitochondria. J Biol Chem 2003; 278: 2356-2360.Zhao Y., Wang Z.B., Xu J.-X. Effect of cytochrome c on the generation and elimination of O2* and H2O2 in mitochondria. J Biol Chem 2003; 278: 2356-2360.

The authors declare that there are no conflicts of interest present.