Effect of 4-(4-chlorobenzyl)pyridine on rat hepatic microsomal cytochrome P450 and drug-metabolizing enzymes in vivo and in vitro

The effect of 4-(4-chlorobenzyl)pyridine (4-CBP) on rat hepatic microsomal cytochrome P450 (P450) and its molecular species (CYP2B1, 2E1, 3A2, 2Cl1, a nd 2Cl2), and on drug-metabolizing enzyme activities were examined in vivo and in vitro. Treatment of rats with 4-CBP resulted in the induction of P45 0 and drug-metabolizing enzymes in a dose-dependent manner, but it,vas mark edly inhibitory at higher dose levels. Immunoblot analyses revealed that 4- CBP induces both CYP2B1 and 2E1; however, both were decreased by increasing the dose of 4-CBP, The in vitro inhibitory experiment revealed that 4-CBP strongly inhibited benzphetamine N-demethylase activity, but not dimethylni trosamine N-demethylase activity.. The present findings pl cn ide informati on on the induction and inhibition effect of chlorinated benzylpyridine on hepatic microsomal P450s and drug-metabolizing enzymes in vivo and in vitro .