Climbazole is a new potent inducer of rat hepatic cytochrome P450.
- 1 January 2001
- journal article
- Published by Japanese Society of Toxicology in The Journal of Toxicological Sciences
- Vol. 26 (3) , 141-150
- https://doi.org/10.2131/jts.26.141
Abstract
We examined the effect of climbazole on the induction of rat hepatic microsomal cytochrome P450 (P450), and compared the induction potency with other N-substituted azole drugs such as clorimazole. We found that climbazole is found to be a potent inducer of rat hepatic microsomal P450 as clorimazole. Induced level of P450 by climbazole was almost similar in extent to clorimazole when compared with other imidazole drugs in a dose- and time-dependent manner. Parallel to the increase in P450, climbazole increased aminopyrine and erythromycin N-demethylase, ethoxycoumarin O-deethylase, and androstenedione 16β- and 15α/6β hydroxylase activities; however, clorimazole did not induce aminopyrine N-demethylase activity irrespective of its marked increase in P450 content. Immunoblot analyses revealed that climbazole induced CYP2B1, 3A2 and 4A1. The present findings indicate that climbazole is a new potent inducer of hepatic microsomal P450 and drug-metabolizing enzymes like clorimazole, but it may have some differential mechanism(s) for these enzymes’ induction in rat liver.Keywords
This publication has 25 references indexed in Scilit:
- Effect of 4-(4-Chlorobenzyl)pyridine on Rat Hepatic Microsomal Cytochrome P450 and Drug-Metabolizing Enzymes in Vivo and in Vitro.Biological & Pharmaceutical Bulletin, 2001
- Concurrent induction of rat hepatic microsomal cytochrome P450 and haem oxygenase by 2,2'-dipyridyl ketone: comparison with the effect of 2,2'-dipyridyl amineXenobiotica, 2000
- Regio-Related Differential Induction of Hepatic Microsomal Heme Oxygenase and Cytochrome P450 by Substituted Imidazole and Pyridine Compounds in Rats.Eisei kagaku, 1996
- Differential Induction of Hepatic and Renal Microsomal Cytochrome P450 by N-Phenylalkylimidazoles in Rats.Eisei kagaku, 1996
- The Induction of Cytochrome P4502E1 by Nitrogen- and Sulfur-Containing Heterocycles: Expression and Molecular RegulationToxicology and Applied Pharmacology, 1993
- Whether cytochrome p450 induction accompanies glucuronosyl and glutathione transferase induction by isomers of dipyridyl appears unrelated to dose and iron chelation propertiesJournal of Biochemical Toxicology, 1992
- Drug metabolizing enzyme induction by simple diaryl pyridines; 2-substituted isomers selectively increase only conjugation enzyme activities, 4-substituted isomers also induce cytochrome P450Toxicology and Applied Pharmacology, 1991
- Acute and subacute effects of miconazole nitrate on hepatic styrene oxide hydrolase and cytochrome P-450-dependent monooxygenase activities in male and female AKR/J miceToxicology, 1988
- Evidence for functional and structural multiplicity of pregnenolone-16.alpha.-carbonitrile-inducible cytochrome P-450 isozymes in rat liver microsomesBiochemistry, 1987
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970