Cytochrome P450 2E1 participation in the pathogenesis of experimental metabolic syndrome in guinea pigs.

Abstract

In this work the experimental metabolic syndrome on the basis of protamine sulfate modeling in guinea pigs was reproduced and pathological processes in the liver of experimental animals were studied. We determined the level of free radicals and markers of liver damage in the blood of experimental animals. We investigated the liver glycogen content and K+,Na+-ATPase activity in the liver of experimental animals as well as measured the cytochrome P450 2E1 (CY P2E1) expression – one of the main factors of oxidative stress. Evidence of development of hepatotoxic processes, increasing of the CY P2E1 level as well as of the free radical level in the animals with metabolic syndrome were found. Using of CY P2E1 inhibitors had shown that the free radical level in the blood of experimental animals depended on the level of the enzyme expression and activity. The obtained results suggest that the changes in the CY P2E1 expression play an important role in the development of hepatotoxic processes upon experimental metabolic syndrome. It was assumed that pharmacological correction of the enzyme expression may be an important mechanism for the influence on the metabolic syndrome clinical course.