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...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2001, Vol.24(5), pp.505-509
Main Authors: KOBAYASHI, Yasuna, OHSHIRO, Naomi, SASAKI, Tadanori, TOKUYAMA, Shogo, TOBE, Takashi, YOSHIDA, Takemi, YAMAMOTO, Toshinori
Format: Article
Language:English
Subjects:
4-(4-chlorobenzyl)pyridine
Animals
Biological and medical sciences
Chemical and industrial products toxicology. Toxic occupational diseases
Cytochrome P-450 CYP2B1 - biosynthesis
Cytochrome P-450 CYP2E1 - biosynthesis
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System - biosynthesis
cytochrome P450
Dose-Response Relationship, Drug
enzyme induction
Enzyme Induction - drug effects
Female
Male
Medical sciences
Microsomes, Liver - enzymology
pyridine
Pyridines - pharmacology
Rats
Rats, Wistar
Solvents
Toxicology
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Summary: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.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.24.505