Reciprocal Modulation of Hepatic Cytochrome P450 Gene Expressions with Streptozotocin Induced Diabetes and Resveratrol

Abstract

Cytochrome P450s are very large and diverse superfamily of hemoproteins found in all domains of life and diverse array of compounds can influence the relative concentrations and/or activities of P450s. Expression of P450s is modulated not only by exposure to various chemicals, but also by some pathophysiological conditions such as diabetes, hypertension and obesity. Six different Cytochrome P450 isoforms namely; 1A1, 2A1, 2E1, 2C11, 3A1, 4A1 were quantified by quantitative Real Time PCR to assess the relative expressions of CYPs mRNA in control and diabetic rat liver tissues. At the same time, effects of resveratrol (RSV) on these isoforms were evaluated. According to results, diabetes enhanced the CYP1A1, CYP2E1 and CYP3A1 gene expression and RSV reduced to these increments toward the control values. Furthermore, while CYP2C11 and CYP4A1 expressions were found to be reduced by diabetes, application of RSV decreased these isoforms’expressions further. Additionally, diabetes and RSV treatment did not alter the CYP2A1&2 expressions significantly.As a result, expressions of cytochrome P450 were altered not only by diabetes but also by exposure to antioxidants such as resveratrol and levels of expressions of each isoforms are important factors determining the biological consequences of xenobiotics and antioxidant defense systems in diabetes

Keywords

• Diabetes, Cytochrome P450, Resveratrol, Real Time PCR.