title: Comparative induction of cytochrome P4504A in rat hepatocyte culture by the peroxisome proliferators, bifonazole and clofibrate.
abstract: 1. The influence of imidazole and triazole antifungal drugs on cytochrome P450 levels in male Wistar primary rat hepatocyte culture for 70 h has been investigated and compared with clofibrate. 2. Bifonazole, clotrimazole, geniconazole clofibrate induced total P450 in hepatocytes, whereas itraconazole, miconazole and UK-47,265 did not. 3. When the CYP4A subfamily was examined, only bifonazole and clofibrate induced CYP4A as assessed by both Western blot analysis and the 11- and 12-hydroxylation of lauric acid. 4. By analysis of concentration-response curves in hepatocyte culture, bifonazole was 160 and 40 times more potent than clofibrate for induction of the 11- and 12-hydroxylation of lauric acid respectively. 5. Taken collectively, our data have identified bifonazole as a relatively potent, non-carboxylate inducer of CYP4A and the mechanism of induction and specificity of this azole is discussed.
authors.affiliation: Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, UK.
authors.forename: O
authors.initials: O
authors.lastname: Sabzevari
authors.forename: M
authors.initials: M
authors.lastname: Hatcher
authors.forename: M
authors.initials: M
authors.lastname: O'Sullivan
authors.forename: P
authors.initials: P
authors.lastname: Kentish
authors.forename: G
authors.initials: G
authors.lastname: Gibson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002994:Clofibrate / Q000494:pharmacology*; D003022:Clotrimazole / Q000494:pharmacology; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D007093:Imidazoles / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008825:Miconazole / Q000494:pharmacology; D008830:Microbodies / Q000187:drug effects; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007093:Imidazoles; D008825:Miconazole; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; D003022:Clotrimazole; D002994:Clofibrate; C036596:bifonazole