Induction of rat hepatic epoxide hydratase by dietary antioxidants.
Induction of rat hepatic epoxide hydratase by dietary antioxidants.
复制标题
通过膳食抗氧化剂诱导大鼠肝环氧化物水合酶。
DOI：
10.1016/0041-008x(79)90315-6
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发表时间：
1979
影响因子：
3.8
通讯作者：
U. Wulff
中科院分区：
文献类型：
--
作者：
R. Kahl;U. Wulff
在大鼠饲料中添加丁基羟基甲苯(BHT)、丁基羟基苯甲醚或乙氧基喹，可提高肝脏环氧化物水合酶活性。0.1%的增幅最为明显，0.5%的增幅达到200-400%。随着活性的提高，在SDS-聚丙烯酰胺凝胶中环氧化物水合酶带的比例增加，这表明该酶是被诱导的。乙氧基香豆素脱乙基酶活性和细胞色素b5浓度适度升高，而细胞色素P-450浓度和芳烃羟基酶活性保持在对照水平。BHT处理后的细胞色素P-450与苯巴比妥处理后的细胞色素P-450的亲和力增强，而非7，8-苯并黄酮对单加氧酶活性的优先抑制作用，以及还原的细胞色素P-450与苯巴比妥的亲和力增强。本研究中使用的抗氧化剂在体外对环氧化物水合酶活性没有影响，只在苯巴比妥刺激的微粒体中抑制单加氧酶的活性，而在3-甲基胆菲刺激的微粒体中不抑制单加氧酶的活性。饲料抗氧化剂和3-甲基胆蒽联合处理可显著诱导环氧化物水合酶活性，而3-甲基胆蒽介导的芳烃羟基酶活性的增加被部分抑制。来自饲喂抗氧化剂的动物的肝微粒体不能有效地催化氚化苯并[a]芘与小牛胸腺DNA的共价结合。经抗氧化剂和3-甲基胆蒽联合处理后，共价结合能力明显降低。抗氧化剂引起的微粒体酶谱变化可能与其抑制化学致癌作用有关。
Supplementation of rat diet with butylated hydroxytoluene (BHT), butylated hydroxyanisole, or ethoxyquin resulted in increased liver epoxide hydratase activity. The increase was obvious at 0.1% and amounted to 200–400% at 0.5%. Increased activity was accompanied by increased proportion of the epoxide hydratase band in SDS polyacrylamide gels, indicating induction of the enzyme. Ethoxycoumarin deethylase activity and cytochrome b5concentrations were moderately elevated while cytochrome P-450 concentrations and aryl hydrocarbon hydroxylase activity remained at control levels. Preferential inhibition of monooxygenase activity by metyrapone and not 7,8-benzoflavone, as well as increased affinity of the reduced cytochrome P-450 for metyrapone as a ligand, indicated that the cytochrome P-450 population after BHT treatment was similar to that found after phenobarbital treatment. The antioxidants used in this study had no in vitro effect on epoxide hydratase activity and inhibited monooxygenase activity only in phenobarbital-stimulated microsomes but not in 3-methylcholanthrene-stimulated microsomes. Combined treatment with dietary antioxidants and intraperitoneally administered 3-methylcholanthrene resulted in marked induction of epoxide hydratase activity while the 3-methylcholanthrene-mediated increase in aryl hydrocarbon hydroxylase activity was partially depressed. Covalent binding of tritiated benzo[a]pyrene to calf thymus DNA was less effectively catalyzed by liver microsomes from animals fed antioxidants. The depression of covalent binding was marked after combined treatment with antioxidants and 3-methylcholanthrene. The shift in the microsomal enzyme pattern caused by antioxidants may be related to their inhibitory effects on chemical carcinogenesis.