Enzyme induction and hepatic glycerolipid synthesis in rats treated with 3-methylcholanthrene.

Abstract

Fasting male rats fed 3-methylcholanthrene in a daily dose of 40 mg . kg body weight-1 gave evidence of hepatic microsomal enzyme induction after 3 days through significantly increased hepatic aryl hydrocarbon hydroxylase activity, cytochrome P448 content, and characteristic changes in microsomal proteins analysed by sodium dodecyl sulfate--polyacrylamide gel electrophoresis. Concomitantly, activities of aminopyrine N-demethylase and microsomal gamma-glutamyltransferase, which are increased in phenobarbital-treated rats, significantly declined. In contrast to phenobarbital, which has been previously shown to increase hepatic triacylglycerol content and in vitro glycerolipid synthesis, 3-methylcholanthrene did not affect hepatic triacylglycerol content, but did inhibit glycerolipid synthesis by cell-free preparations of rat liver and significantly reduced serum triacylglycerol concentration. Thus, the two prototypical drugs inducing characteristically different changes in microsomal enzyme and hemoprotein response also seem to differ in their effect upon another important microsomal function, hepatic glycerolipid synthesis.