Clotrimazole-induced modulation of hepatic cytochrome P450 enzymes in Syrian and Chinese hamsters.
Clotrimazole, an imidazole antifungal drug, is known to induce cytochrome P450 isozymes of the P450IIIA and P450IIB subfamilies in rats. This agent modulated hepatic cytochrome P450 enzymes differently in golden Syrian and Chinese hamsters and also in hamsters and rats. Clotrimazole at a daily intraperitoneal dose of 100 mg/kg for three days increased the amount of cytochrome P450 in the livers of the two hamster strains. In Syrian hamsters, clotrimazole significantly induced the activities of 7-pentoxyresorufin O-dealkylase, coumarin 7-hydroxylase, benzphetamine N-demethylase and testosterone 15 alpha- and 16 alpha-hydroxylases, but reduced those of testosterone 15 beta-, 7 alpha-, 6 beta-, 2 alpha- and 2 beta-hydroxylases. In Chinese hamsters, clotrimazole markedly stimulated the activities of coumarin 7-hydroxylase and testosterone 15 alpha, 16 alpha- and 2 alpha-hydroxylases as well as the formation of androstenedione. Western blot analysis revealed that clotrimazole treatment induced mainly cytochrome P450 isozymes immunorelated to the P450IIB and P450IIA subfamilies in Syrian hamsters and isozymes immunorelated to the P450IIA subfamily in Chinese hamsters. In contrast, in both hamster strains, clotrimazole did not induce the isozymes corresponding to the P450IIIA subfamily.
Antignac
E
E
Department of Pharmaceutical Sciences, Institute of Public Health, Tokyo, Japan.
Fakuhara
M
M
Kimura
M
M
Ushio
F
F
D000818:Animals; D015153:Blotting, Western; D003022:Clotrimazole / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D006900:Hydroxylation / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D013739:Testosterone / Q000378:metabolism
D007527:Isoenzymes; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D003022:Clotrimazole