Oxidative stress in the human heart is associated with changes in the antioxidative defense as shown after heart transplantation

Molecular and Cellular Biochemistry - Tập 204 - Trang 89-96 - 2000
Ingolf Schimke1, Martin Schikora1, Rudolf Meyer2, Hans-Peter Dübel1, Diethelm Modersohn3, Franz Kleber4, Gert Baumann1
1Medizinische Klinik (Kardiologie, Angiologie, Pneumologie), Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Berlin, Germany
2Deutsches Herzzentrum Berlin, Berlin, Germany
3Klinik für Kardiovaskuläre Chirurgie, Universitätsklinikum Chartiét Humboldt-Universität zu Berlin, Berlin, Germany
4Unfallkrankenhaus Berlin, Berlin, Germany

Tóm tắt

The study was designed to demonstrate - for the first time in humans - that oxidative stress in the heart indicated by lipid peroxidation is associated with time--dependent changes in the enzymatic antioxidative defense. For this purpose, we analyzed the oxygen radical metabolism in 69 myocardial biopsies (taken between the fifth day and 6 years after transplantation) of 31 heart transplant recipients who were suspected of suffering from increased formation of oxygen radicals in the allograft. The levels of lipid peroxides (LPO), glutathione peroxidase (GSH-Px), total-, copper/zinc- and manganese superoxide dismutase (t-SOD, CuZnSOD, MnSOD) were compared in 3 post-transplantation periods (5-90 d vs. 91-365 d vs. 1 y). Significantly increased LPO levels were found (0.27±0.04 vs. 0.13±0.02 vs. 0.27±0.04 nmol/mg protein) in the first and third period. Increased activities of GSH-Px (39.8±3.8 vs. 30.2±4.1 vs. 76.±6.5 mU/mg protein), t-SOD (1.57±0.10 vs. 1.30±0.14 vs. 2.44±0.23 U/mg protein) and CuZnSOD (1.09±0.08 vs. 0.93±0.13 vs. 2.05±0.21 U/mg protein) occurred only in the third period. For calculation of time courses more precisely, the single data with respect to time were analyzed with a curve fitting program. Except for the first period, the allograft LPO and GSH-Px levels rose for up to 6 years after transplantation. However, the t-SOD and CuZnSOD activities switched from increase to decrease in the third period. The study provided indication for: first, the potency of the human heart to time-limited increase of the enzymatic antioxidative defense, and secondly, the inability of human heart allografts - despite this adaptation - for complete prevention of myocardial oxidative stress.

Từ khóa


Tài liệu tham khảo

Coetzee IH, Lochner A: Free radical effects on myocardial membrane microviscosity. Cardioscience 4: 205-215, 1993

Kaneko M, Matsumoto Y, Hayashi H, Kobayashi A, Yamazaki N: Oxygen free radicals and calcium homeostasis in the heart. Mol Cell Biochem 139: 91-100, 1994

Schimke I, Haberland A, Will-Shahab L, Küttner I, Papies B: In vitro effects of reactive O2 species on the myocardial β-receptoradenylyl cyclase-system. Mol Cell Biochem 110: 41-46, 1992

Singal PK, Kirshenbaum LA: A relative deficit in antioxidant reserve may contribute in cardiac failure. Can J Cardiol 6: 47-49, 1990

Billigham ME, Berry GJ: The pathology of cardiac transplantation. In: S.J. Shumway, and N.E. Shumway (eds). Thoracic Transplantation. Blackwell Science, Cambridge, 1995, pp 309-347

Belch JJ, Bridges AB, Scott N, Chopra M: Oxygen free radicals and congestive heart failure. Br Heart J 65: 245-248, 1991

Schimke I, Haberland A: Sauerstoff-Radikale und Herz-Kreislauf-Krankheiten: Pathogenetische Mechanismen, therapeutische Möglichkeiten. Z Kardiol 82: 601-609, 1993

Dhalla AK, Singal PK: Antioxidant changes in hypertrophied and failing guinea pig heart. Am J Physiol 266: H1280-1285, 1994

Witztum JL: The oxidation hypothesis of atherosclerosis. Lancet 344: 793-7935, 1994

Ghatak A, Brar MJ, Agarwal A, Goel N, Rastogi AK, Vaish AK, Sircar AR, Chandra M: Oxy free radical system in heart failure and therapeutic role of oral vitamin E. Int J Cardiol 57: 119-127, 1996

Boyle EM, Shumway SJ, Bolman III RM: Immunosuppression regimens in thoracic transplantation. In: S.J. Shumway and N.E. Shumway (eds). Thoracic Transplantation. Blackwell Science, Cambridge, 1995, pp 195-204

Ohkawa H, Ohishi N, Yagi K: Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem 95: 351-358, 1978

Beauchamp C, Fridovich I: Superoxide dismutase: improved assay and an assay applicable to acrylamide gels. J Anal Biochem 44: 276-287, 1971

Mizuno Y: Changes in superoxide dismutase, catalase, glutathion peroxidase, and glutathione reductase activities and thiobarbituric acid-reactive products levels in early stages of development in dystrophic chickens. Exp Neurol 84: 58-73, 1984

Paglia DE, Valentine WN: Studies on the quantitative and qualitative characterization of erythrocytes glutathione peroxidase. J Lab Clin Med 29: 143-148, 1967

Billingham ME, Cary NRB, Hammond ME, Kemnitz J, Marboe CH, McCallister HA, Snovar DC, Winters GL, Zerbe A: A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: Heart rejection study group. J Heart Transplant 9: 587-593, 1990

Hosenpud JD, Novick RJ, Breen TJ, Keck BM, Daily DP: The Registry of the International Society for Heart and Lung Transplantation. Twelfth Official Report–1995. J Heart & Lung Transplant 15: 655-674, 1996

Edes I, Piros G, Forster T, Csanady M: Alcohol-induced congestive cardiomyopathy in adult turkeys: effects on myocardial antioxidant defence systems. Basic Res Cardiol 82: 551-556, 1987

Zheng YM: The relationship between experimental myocardial hypertrophy and oxygen free radicals. Ching Hua Hsin Hsueh Kuan Ping Tsa Chinh 21: 379-382, 1993

Gupka M, Sigal PK: Higher antioxidative capacity during a chronic stable heart hypertrophy. Circ Res 64: 398-406, 1989

Coles JG, Romaschin AD, Wilson GJ, Mickle DA, Dasmahapatra H, Martell M, Mehra A, Tsao P: Oxygen free radical-mediated lipid peroxidation injury in acute cardiac allograft rejection. Transplantation 54: 175-178, 1992

Kloc M, Mailer K, Stepowski S: Superoxide dismutase decrease in cardiac transplants. Transplantation 41: 794-796, 1986

Roza AM, Pieper G, Moore-Hilton G, Johnson CP, Adams MB: Free radicals in pancreatic and cardiac allograft rejection. Transpl Proc 26: 544-555, 1994

Sobotka PA, Gupka DK, Lansky DM, Costano MR, Zarling EJ: Breath pentane is a marker of acute cardiac allograft rejection. J Heart & Lung Transplant 13: 224-229, 1994

Auer T, Khoschsorur GA, Rabl H, Iberer F, Petutschnigg B, Wasler A, Tscheliessnigg KH: Detection of lipid peroxidation products by malondialdehyde (MDA-TBA reaction) in organ transplantation. Transplant Proc 27: 2749-2751, 1995

Chancerelle Y, de Lorgeril M, Viret R, Chiron B, Dureau G, Renaud S, Kergonou JF: Increased lipid peroxidation in cyclosporin-treated heart transplant recipients. Am J Cardiol 68: 813-816 1991

de Lorgeril M, Richard MJ, Arnaud J, Boissonat P, Guidollet J, Dureau G, Renaud S, Favier A: Lipid peroxides and antioxidant defenses in accelerated transplantation-associated coronary arteriosclerosis. Am Heart J 125: 974-980, 1993

Janero DR: Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 9: 515-540, 1990

Bondo K, Senoo Y: Oxygen-derived free radical damage in canine heart transplantation. J Surg Res 46: 152-156, 1989

Vreugdenhil PK, Belzer FO, Southard JH: Effect of cold storage on tissue and cellular glutathione. Cryobiology 28: 143-149, 1991

Janssen M, Kostner JF, Bos E, de Jong JM: Malondialdehyde and glutathione production in isolated perfused human and rat hearts. Circ Res 73: 681-688, 1993

Lehmann I, Papies B, Parsi RA, Romaniuk P, Schimke I, Parsi E, Koenig ML, Wagenknecht C: Enzyme pattern and lipid peroxides in endomyocardial biopsies from patients with cardiomyopathy and myocarditis. Clin Chim Acta 173: 193-200, 1988

Nowak D, Zieba M, Zawiasa D, Rozniecki J, Krol M: Changes of serum concentration of lipid peroxidation products in patients with pneumonia. Monardi Arch Chest Dis 51: 188-93, 1996

Schwarz KB: Oxidative stress during viral infection: a review. Free Radic Biol Med 21: 641-649, 1996

Kanter KR, Hertzler GL, Gravanis MB: Cardiac transplantation. In: M.B. Gravanis (ed). Cardiovascular Disorders. Pathogenesis and Pathophysiology. Mosby, St Louis, 1993, pp 463-488

Miyazawa T, Suzuki T, Fujimoto K, Kinoshita M: Age-related changes of phosphatidylcholine hydroperoxide and phosphatidyletanolamine hydroperoxide levels in normal human red blood cells. Mech Ageing Dev 86: 145-150, 1996

Schimke I, Romaniuk P, Schimke E, Papies B: Konzentration von Thiobarbitursäure-reaktiver Substanzen im Plasma von Patienten mit Atherosklerose unterschiedlicher Lokalisation und unterschiedlichen Schweregrades. Z Med Lab Diagn 31: 176-180, 1990

Kumar KV, Das UN. Are free radicals involved in the pathology of human essential hypertension. Free Radic Res Commun 19: 59-66, 1993

Schimke I, Schimke E: Plasma concentration of thiobarbituric acid reactive substances (TBARS) in type I diabetics. Diabetes Research 21: 65-72, 1992

Niwa Y, Ilizawa O, Ishimoto K, Akamatsu H, Kanoh T: Agedependent basal level and induction capacity of copper-zinc and manganese superoxide dismutase and other scavenging enzyme activities in leukocytes from young and elderly adults. Am J Pathol 143: 312-320, 1993

Sohal RS, Agarwal S, Sohal BH: Oxidative stress and aging in the Mongolian gerbil (Meriones unguiculatus). Mech Ageing Dev 81: 15-25, 1995

Haberland A, Henke W, Grune T, Siems W, Jung K, Schimke I: Different response of the oxygen radical metabolism in rat heart, liver and kidney on cyclosporine A treatment. Inflamm Res 46: 452-454, 1997

le Gal YM, Scott T, Prabhakaran VM, Zhang J, Pushpanathan C, Morrissey L: Heart-lung protection from ischemic injury during 8 hour hypothermic preservation. Acta Biomed Ateneo Parmense 65: 181-198, 1994

Lapenna D, Mezzetti A, de Gioia S, Pierdomenico SD, Verna AM, Daniele F, Marzio L, di Ilio C, Clafiore AM, Cuccurullo F: Blood cardioplegia reduces oxidant burden in the ischemic and reperfused human myocardium. Ann Thorac Surg 57: 1522-1525, 1994

Slakey DP, Roza AM, Pieper GM, Johnson CP, Adams MB: Delayed cardiac allograft rejection due to combined cyclosporine and antioxidant therapy. Transplantation 56: 1305-1309, 1993