Apoptosis of cardiomyocytes assessed by a novel apoptotic marker [annexin V] and the role of vitamin E in cardioprotection in diabetic rats

ABSTRACT

Recently it has been shown that annexin V is an apoplolic marker in the heart. The aim of the present study was to explore whether annexin V content in the heart changes during diabetes in order to use it as a prognostic tailor in diabetic cardiac affection. In addition, the study attempted to show the effect of treatment of insulin and vitamin E [300mg and 600mg/Kg] used separately or in combination. The study included 70 male albino rats weighing I70-200gm. They were divided into the following groups of 10 rats each Group I [cont] Control group, Group II [DM] Diabetic, untreated group. Diabetes was induced by intraperitoneal injection of streptozotocin [stz] at a dose of 40mg/kg body weight, Group III [Ins] Diabetic group, treated with 1 unit insulin injected subcutaneously, Group IV [E-300] Diabetic group, receiving 300mg/kg vitamin E injected intramuscularly, 3 times/week for one month, Group V [E-600] Diabetic group, receiving vitamin E i.m injection at a dose of 600mg/kg, 3 times/week for one month, Group VI [I+E-300] Diabetic group treated with insulin and vitamin E [300mg/kg/dose] and Group VII [I+E-600] Diabetic group treated with insulin and vitamin E [600mg/kg/dose]. Annexin V and inducible nitric oxide synthase [iNOS] were examined in the hearts of animals by RT-PCR. Also, cGMP, malondialdehyde [MDA], glutathione peroxidase [GPX] and cardiac enzymes were measured. There were three major new findings in the present study. First; annexin V levels were significantly elevated in the heart of diabetic rats compared to controls. This elevation in annexin V content indicates that apoptosis is the basis of cardiac injury as shown by the elevated cardiac enzymes AST, ALT and CPK. Second, levels of iNOS protein of the heart were elevated in diabetic rats. On the basis of theses findings, we can suggest that inflammation could play a role in the pathogenesis of diabetic cardiomyopathy in type I diabetes. Third, the effect of various types of treatment of diabetes which were used here showed the beneficial effects of the use of the antioxidant, vitamin E. These results suggest that annexin V can be used as a prognostic factor in cardiac affection in DM. In addition, they provide further evidence that pharmacological intervention by different antioxidants may have significant implications in the prevention of the pro-oxidant features of diabetes