Attenuation of Hyperinsulinemia-induced DNA Damage of Peripheral Lymphocytes by Carvedilol

Abstract

Context: Most people with diabetes suffer from cardiovascular problems; however, increased oxidative stress caused by diabetes can increase the risk of DNA damage and cancer. Carvedilol is a third-generation beta-blocker that can both improve heart function and prevent oxidative stress. Aims: The present study aimed to assess carvedilol’s genoprotective effects against hyperinsulinemia-induced DNA strand break in rats. Materials and Methods: To evaluate the extent of DNA damage caused by high insulin concentrations and the effect of carvedilol on these lesions, isolated lymphocytes of high-fat type 2 diabetic rats were evaluated using the comet method. Results: Our results in this study using the comet method showed that hyperinsulinemia and hyperglycemia of high-fat diet have significant genotoxic parameters in rats (tail length 84.35 ± 0.23 vs. 0.90 ± 0.02, % DNA in tail 16.09 ± 0.09 vs. 7.63 ± 0.04, and tail moment 13.58 ± 0.09 vs. 0.07 ± 0.01) compared with the control group (P < 0.001). In rats receiving carvedilol, we observed the genoprotective effect in a dose-dependent manner, which is predicted due to the antioxidant activity of carvedilol and its metabolites. Conclusion: It does not have an adverse effect on the blood sugar profile of diabetics and reduction of cardiovascular complications of the disease; carvedilol can prevent genetic damage and cancer risk in hyperinsulinemia induced by the high-fat diet.