Clotrimazole induction of cytochrome P-450: dose-differentiated isozyme induction.
Mol Pharmacol
; 31(2): 135-9, 1987 Feb.
Article
en En
| MEDLINE
| ID: mdl-3100941
Treatment of male rats for 3 days with the N-substituted imidazole, clotrimazole, produced up to a 4-fold induction of hepatic microsomal cytochrome P-450. The monooxygenase activities induced varied with the dose administered. At low doses (less than 25 mg/kg), p-nitroanisole demethylase and aniline hydroxylase activities were induced. Only at higher doses were other monooxygenase activities (erythromycin and ethylmorphine demethylases and cytochrome P-450 metabolic-intermediate complex formation from troleandomycin) induced. Microsomal UDP-glucuronosyltransferase activity toward morphine was induced at low doses in a manner similar to that of p-nitroanisole demethylase. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of microsomes indicated that low doses of clotrimazole caused the intensification of a 48,000 molecular weight protein band, whereas at high doses, there was a marked intensification of an additional 50,500 molecular weight protein, the same molecular weight band as was intensified in phenobarbital- and dexamethasone-induced microsomes. The observations suggest a phenomenon of "dose-differentiated" isozyme induction for cytochrome P-450.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Microsomas Hepáticos
/
Clotrimazol
/
Sistema Enzimático del Citocromo P-450
/
Oxigenasas de Función Mixta
/
Imidazoles
Límite:
Animals
Idioma:
En
Revista:
Mol Pharmacol
Año:
1987
Tipo del documento:
Article
Pais de publicación:
Estados Unidos