亚甲二氧基苯基化合物对细胞色素P-450的诱导作用：亚甲基碳的重要性。

Induction of cytochrome P-450 by methylenedioxyphenyl compounds: importance of the methylene carbon.

作者信息

Cook J C, Hodgson E

出版信息

Toxicol Appl Pharmacol. 1983 Mar 30;68(1):131-9. doi: 10.1016/0041-008x(83)90362-9.

Abstract

Induction of hepatic microsomal cytochrome P-450 in Dub:ICR male mice treated with phenobarbital, 3-methylcholanthrene, safrole, isosafrole, 5-tert.-butyl-1,3-benzodioxole (BBD), 2-methyl-5-tert.-butyl-1,3-benzodioxole (MBBD), and 2,2-dimethyl-5-tert.-butyl-1,3-benzodiozole (DBBD) was evaluated by measuring the cytochrome P-450 content, Type II:Type 1 binding ratio, ethylisocyanide pH equilibrium point, biphenyl 2- and 4-hydroxylase, ethylmorphine N-demethylase, ethoxyresorufin O-deethylase, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Safrole and isosafrole treatment of mice produced a phenobarbital-type induction. BBD, but not MBBD and DBBD, induced cytochrome P-450 and formed a Type III metabolite-cytochrome P-450 complex, in vitro and in vivo. SDS-PAGE revealed that DBBD does induce proteins other than cytochrome P-450. These data suggest that the methylene carbon plays an important role in cytochrome P-450 induction.

摘要

通过测量细胞色素P-450含量、II型与I型结合比率、乙基异氰酸酯pH平衡点、联苯2-和4-羟化酶、乙基吗啡N-脱甲基酶、乙氧异羟肟酸O-脱乙基酶以及十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE），评估用苯巴比妥、3-甲基胆蒽、黄樟素、异黄樟素、5-叔丁基-1,3-苯并二恶唑（BBD）、2-甲基-5-叔丁基-1,3-苯并二恶唑（MBBD）和2,2-二甲基-5-叔丁基-1,3-苯并二恶唑（DBBD）处理的Dub:ICR雄性小鼠肝微粒体细胞色素P-450的诱导情况。用黄樟素和异黄樟素处理小鼠产生了苯巴比妥型诱导。BBD在体内外均诱导细胞色素P-450并形成III型代谢物-细胞色素P-450复合物，而MBBD和DBBD则未诱导。SDS-PAGE显示DBBD确实诱导了除细胞色素P-450之外的蛋白质。这些数据表明亚甲基碳在细胞色素P-450诱导中起重要作用。