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, 2C11, and 2C12), and on drug-metabolizing enzyme activities were examined in vivo and in vitro. Treatment of rats with 4-CBP resulted in the induction of P450 and drug-metabolizing enzymes in a dose-dependent manner, but it was markedly 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 dimethylnitrosamine N-demethylase activity. The present findings provide information on the induction and inhibition effect of chlorinated benzylpyridine on hepatic microsomal P450s and drug-metabolizing enzymes in vivo and in vitro.
Kobayashi
Y
Y
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Ohshiro
N
N
Sasaki
T
T
Tokuyama
S
S
Tobe
T
T
Yoshida
T
T
Yamamoto
T
T
D000818:Animals; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D065607:Cytochrome P-450 Enzyme Inhibitors; D011725:Pyridines; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D019362:Cytochrome P-450 CYP2B1