Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
권호 표지

Effect of Antioxidants on Myocardial Damage in Streptozotocin-Induced Diabetic Rats

당뇨 유발 백서에서의 심근손상에 대한 항산화제 효과

Koh, Jong-Hoon;Ryu, Kyu-Hyung;Lim, Sung-Hee;Hong, Kyung-Soon;Choi, Yung-Jin;Park, Sung-Woo
고종훈;유규형;임성희;홍경순;최영진;박성우

  • Published : 20060000
⟨ Previous Next ⟩

Abstract

Background and Objectives：Many diabetic patients suffer from cardiomyopathy, even in the absence of vascular disease. The aim of this study was to see if dietary antioxidant supplementation has an inhibitory effect on the progression of cardiac tissue damage in streptozotocin (STZ)-induced diabetic rats. Materials and Methods：Sprague-Dawley male rats (n=60) were used as experimental animals; they were divided into the normal control group and the diabetic group. Eight weeks after STZ injection (65 mg/kg of body weight), the products of lipid peroxidation (malondialdehydes, MDA), and the antioxidant enzyme superoxide dismutase (SOD), and catalase activities were determined in the cardiac tissue homogenates. The cardiac tissues were studied by light microscopy (LM) and electron microscopy (EM), and the tissue lesions were graded by a semiquantitative score. Results：The histologic scores for perivascular fibrosis, interstitial fibrosis and myocardial necrosis according to LM were significantly lower in the combined vitamin C & E treated rats than in the diabetic control rats. The ultrastructural scores for the overall cardiac morphology, mitochondria and myofilaments, according to EM, were significantly lower in the vitamin E treated rats and the combined vitamin C & E treated rats than in the diabetic control rats, even though this was of less magnitude than that in the insulin-treated diabetic rats. Conclusion：These results suggest that antioxidants such as vitamin C & E might have a beneficial effect on diabetes as an adjunct therapy against lipid peroxidation and diabetic cardiomyopathy, in addition to the effects of instituting strict measures for controlling the blood glucose. (Korean Circulation J 2006;36:261-271)

Keywords

References

  1. Shapiro LM, Leatherdale BA, Coyne ME, Fletcher RF, Mackinnon J. Prospective study of heart disease in untreated matureity onset diabetics. Br Heart J 1980;44:342-8 https://doi.org/10.1136/hrt.44.3.342
  2. Ryu WS, Ryoo UH, Seo JD, Lee YW. A study on the cardiac myofifillar ATPase actitity in Diabetic rats. Korean Circ J 1987;17: 479-90 https://doi.org/10.4070/kcj.1987.17.3.479
  3. Scott JA, King GL. Oxidative stress and antioxidant treatment in diabetes. Ann NY Acad Sci 2004;1031:204-13 https://doi.org/10.1196/annals.1331.020
  4. Yan SD, Schmidt AM, Anderson GM, et al. Enhanced cellular oxidant stress by the interaction of advanced glycosylation end products with their receptors/binding proteins. J Biol Chem 1994; 269:9889-97
  5. Gonzalez-Vilchez F, Ayuela J, Ares M, Pi J, Castillo L, Martin- Duran R. Oxidative stress and fibrosis in incipient myocardial dysfunction in type 2 diabetic patients. Int J Cardiol 2005;101:53-8 https://doi.org/10.1016/j.ijcard.2004.03.009
  6. Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 1999;48:1-9 https://doi.org/10.2337/diabetes.48.1.1
  7. Ceriello A. New insights on oxidative stress and diabetic complications may lead to a 'causal' antioxidant therapy. Diabetes Care 2003;26:1589-96 https://doi.org/10.2337/diacare.26.5.1589
  8. Jun JE, Jong H, Chun BY, et al. Effect of antioxidant supplementation on the lipid peroxidation and antioxidative enzyme activities in patients with coronary heart disease. Korean Circ J 2001;31:1215-24 https://doi.org/10.4070/kcj.2001.31.11.1215
  9. Jain SK, Krueger KS, McVie R, Jaramillo JJ, Palmer M, Smith T. Relationship of blood thromboxane-B2 (TxB2) with lipid peroxides and effect of vitamin E and placebo supplementation on TxB2 and lipid peroxide levels in type 1 diabetic patients. Diabetes Care 1998;21:1511-6 https://doi.org/10.2337/diacare.21.9.1511
  10. On YK, Chung WY, Chae IH, et al. Improvement in endothelial by angiotensin-converting enzyme Inhibitor and vitamin C in essential hypertension. Korean Circ J 2001;31:411-9 https://doi.org/10.4070/kcj.2001.31.4.411
  11. Ting HH, Timimi FK, Boles KS, Creager SJ, Ganz P, Creager MA. Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1996;97:22-8 https://doi.org/10.1172/JCI118394
  12. Karasu C, Ozansoy G, Bozkurt O, Erdogan D, Omeroglu S. Antioxidant and triglyceride-lowering effects of vitamin E associated with the prevention of abnormalities in the reactivity and morphology of aorta from streptozotocin-diabetic rats: Antioxidants in Diabetes-induced Complications (ADIC) study group. Metabolism 1997;46:872-9 https://doi.org/10.1016/S0026-0495(97)90072-X
  13. Fiordaliso F, Bianchi R, Staszewsky L, et al. Antioxidant treatment attenuates hyperglycemia-induced cardiomyocyte death in rats. J Mol Cell Cardiol 2004;37:959-68 https://doi.org/10.1016/j.yjmcc.2004.07.008
  14. Liang Q, Carlson EC, Donthi RV, Kralik PM, Shen X, Epstein PN. Overexpression of metallothionein reduces diabetic cardiomyopathy. Diabetes 2002;51:174-81 https://doi.org/10.2337/diabetes.51.1.174
  15. Ye G, Metreveli NS, Donthi RV, et al. Catalase protects cardiomyocyte function in models of type 1 and type 2 diabetes. Diabetes 2004;53:1336-43 https://doi.org/10.2337/diabetes.53.5.1336
  16. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95: 351-8 https://doi.org/10.1016/0003-2697(79)90738-3
  17. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974;47:469-74 https://doi.org/10.1111/j.1432-1033.1974.tb03714.x
  18. Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121-6 https://doi.org/10.1016/S0076-6879(84)05016-3
  19. Akula A, Kota MK, Gopisetty SG, et al. Biochemical, histological and echocardiographic changes during experimental cardiomyopathy in STZ-induced diabetic rats. Pharmacol Res 2003;48: 429-35 https://doi.org/10.1016/S1043-6618(03)00191-9
  20. Shoff SM, Mares-Perlman JA, Cruickshanks KJ, Klein R, Klein BE, Ritter LL. Glycosylated hemoglobin concentrations and vitamin E, vitamin C, and beta-carotene intake in diabetic and nondiabetic older adults. Am J Clin Nutr 1993;58:412-6 https://doi.org/10.1093/ajcn/58.3.412
  21. Diepeveen SH, Verhoeven GW, van der Palen J, et al. Effects of atorvastatin and vitamin E on lipoproteins and oxidative stress in dialysis patients: a randomized-controlled trial. J Intern Med 2005;257:438-45 https://doi.org/10.1111/j.1365-2796.2005.01484.x
  22. Fernandez-Robredo P, Moya D, Rodriguez JA, Garcia-Layana A. Vitamins C and e reduce retinal oxidative stress and nitric oxide metabolites and prevent ultrastructural alterations in porcine hypercholesterolemia. Invest Ophthalmol Vis Sci 2005;46:1140-6 https://doi.org/10.1167/iovs.04-0516
  23. Muruganandan S, Gupta S, Kataria M, Lal J, Gupta PK. Mangiferin protects the streptozotocin-induced oxidative damage to cardiac and renal tissues in rats. Toxicology 2002;176:165-73 https://doi.org/10.1016/S0300-483X(02)00069-0
  24. Haider B, Yeh CK, Thomas G, Oldewurtel HA, Lyons MM, Regan TJ. Influence of diabetes on the myocardium and coronary arteries of rheums monkeys fed an atherogenic diet. Circ Res 1981;49:1278-88 https://doi.org/10.1161/01.RES.49.6.1278
  25. Dillmann WH. Diabetes mellitus induces changes in cardiac myosin of the rat. Diabetes 1980;29:579-82 https://doi.org/10.2337/diab.29.7.579
  26. Koltai MZ, Balogh I, Wagner M, Pogatsa G. Diabetic myocardial alterations in ultrastructure and function. Exp Pathol 1984;25: 215-21 https://doi.org/10.1016/S0232-1513(84)80023-7
  27. Regan TJ, Wu CF, Yeh CK, Oldewurtel HA, Haider B. Myocardial composition and function in diabetes: the effect of the chronic insulin use. Circ Res 1981;49:1268-77 https://doi.org/10.1161/01.RES.49.6.1268
  28. Mirsky I, Laks MM. Time course of changes in the mechanical properties of the canine right and left ventricles during hypertrophy caused by pressure overload. Circ Res 1980;46:530-42 https://doi.org/10.1161/01.RES.46.4.530
  29. Thompson EW. Structural manifestations of diabetic cardiomyopathy in the rats and its reversal by insulin treatment. Am J Anat 1988;182:270-82 https://doi.org/10.1002/aja.1001820308
  30. Granado F, Olmedilla B, Gil-Marinez E, Blanco I, Millan I, Rojas- Hidalgo E. Carotenoids, retinol and tocopherols in patients with insulin-dependent diabetes mellitus and their immediate relatives. Clin Sci 1998;94:189-95 https://doi.org/10.1042/cs0940189