Antiapoptotic effect of carvedilol and vitamin E in diabetic nephropathy and cardiomyopathy

ABSTRACT

Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has close connection with antioxidant stress destruction in many diseases including diabetes. BcI-2 gene also has anti apoptotic effect. Carvedilol, is novel beta-adrenoreceptor blocker, which has antioxidant and free radical scavenger properties. In physicochemical, biochemical and cellular assay carvedilol inhibited the formation of reactive oxygen radicals and lipid peroxidation and prevented the depletion of endogenous antioxidants. Moreover, it was reported that carvedilol enhanced the expression of Bcl-2 gene which has antioxidant and anti-apoptotic effects. There are few researches on the effect of Carvedilol on diabetic cardiomyopathy and nephropathy. Whether carvedilol can improve cardiac or renal function in diabetic animal models and the ability of carvedilol to express the Bcl-2 gene and compare its antioxidant effect with a traditional antioxidant like vitamin E is our aim of the current study. In this study we used streptozotocin to induce diabetes mellitus in male albino rats, we investigated carvedilol-administrated in healthy and streptozotocin-induced diabetic rats for 6 weeks as well as vitamin E to compare their effects on biochemical parameters [blood glucose level, lipid profile, serum levels of thiobarbetioric acid [TBAS] and total antioxidant status [TAOS], renal function tests, creatinin phosphokinase [CPK], expression of Bcl-2 protein in the cardiac and renal tissues and histopathological examination in the cardiac and renal tissues. The study showed that, the diabetic rats not only had cardiac and renal dysfunction, high levels of blood glucose and lipid peroxide, lower levels of TAOS, but also showed lower expression of Bcl-2 protein. Carvedilol and vitamin E treatments improved renal and cardiac functions, lowered blood glucose, serum lipids and lipid peroxide, increased levels of TAOS and expression of Bcl-2 protein in healthy rats as well as diabetic rats. In addition they have protective effects on cardiac and renal tissues. These results indicated that carvedilol and vitamin E partly improve cardiac and renal function via their antioxidant properties in diabetic rats