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Induction of cytochrome P-450 isozymes by chromanamine derivatives in rat liver.
Tsukidate, K; Sagami, F; Horie, T; Fukuda, T; Kitada, M; Kanakubo, Y.
Afiliación
  • Tsukidate K; Tsukuba Research Laboratory, Eisai Co. Ltd, Ibaraki, Japan.
Xenobiotica ; 19(8): 901-12, 1989 Aug.
Article en En | MEDLINE | ID: mdl-2815832
1. Pretreatment of rats with 6-(3-picolyl)amino-2,2,5,8-tetramethylchromane (PATC) for 7 days resulted in a significant increase in the activities of benzphetamine N-demethylase, p-nitroanisole O-demethylase and aniline hydroxylase in liver microsomes prepared 24 h after the last treatment. 2. Analysis by Western blot showed that PATC induces cytochrome P-450 b, P-450 c and P-450 d, which are the major forms of cytochrome P-450 in liver microsomes of rats when pretreated with phenobarbital and 3-methylcholanthrene. 3. Exposure of liver sections to the antibodies to cytochrome P-450 b and P-450 c resulted in intense immunostaining within the centrilobular regions, but produced staining of considerably weaker intensity in the perilobular region. Semiquantitative immunochemical analysis, by image analyser, of cytochrome P-450 b and P-450 c showed that centrilobular hepatocytes were stained more intensively than perilobular hepatocytes. 4. These results indicate that PATC induces cytochromes P-450 b and P-450 c, in the centrilobular hepatocytes to a greater degree than those in the perilobular hepatocytes. 5. Co-administration of PATC with pentobarbital caused a significant increase in pentobarbital sleeping time. Furthermore, PATC was found to cause a decrease in the activity of benzphetamine N-demethylase in liver microsomes prepared 30 min after treatment with the drug.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Picolinas / Benzopiranos / Cromanos / Sistema Enzimático del Citocromo P-450 / Hígado Límite: Animals Idioma: En Revista: Xenobiotica Año: 1989 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Picolinas / Benzopiranos / Cromanos / Sistema Enzimático del Citocromo P-450 / Hígado Límite: Animals Idioma: En Revista: Xenobiotica Año: 1989 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido