Species and strain differences in the butylated hydroxytoluene (BHT)-producing induction of hepatic drug oxidation enzymes.
Species and strain differences in the butylated hydroxytoluene (BHT)-producing induction of hepatic drug oxidation enzymes.
复制标题
产丁基羟基甲苯（BHT）诱导肝药物氧化酶的物种和菌株差异。
DOI：
10.1254/jjp.30.861
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
K. Hiraga
中科院分区：
文献类型：
--
作者：
S. Kawano;T. Nakao;K. Hiraga
5周龄Wistar-JCL雄性和雌性大鼠以及C57 BL/6 N雄性小鼠给予含0.5%丁基羟基甲苯（BHT）的饲料6天，导致肝脏重量和微粒体蛋白含量显著增加。然而，细胞色素P-450含量和药物氧化活性的增加更为显著，即在体重基础上分别观察到2.5倍和3倍以上的增加。BHT诱导的细胞色素P-450与苯巴比妥诱导的细胞色素在许多方面不能区分：（1）广泛的底物特异性;（2）CO结合差谱无蓝移;（3）异氰乙烷差谱峰高比无升高;（4）α-萘醌对对硝基茴香醚脱甲基酶活性无抑制作用; 5）SDS-聚丙烯酰胺凝胶电泳显示分子量为50，000和54，000的多肽明显增加。然而，BHT在大鼠中对46，000分子量多肽的诱导比PB更明显，在小鼠中未观察到这种诱导。与这种明显的诱导相反，对MC无反应的DBA/2N小鼠给予BHT既不产生肝肿大，也不诱导细胞色素，但没有产生极高的死亡率。
Five week-old, Wistar-JCL male and female rats and C57BL/6N male mice give a 0.5% butylated hydroxytoluene (BHT)-containing diet for 6 days produced a marked increase in hepatic weight and microsomal protein content. However, the augmentations of cytochrome P-450 content and drug oxidation activities were much more significant, i.e. 2.5-fold and more than three-fold increases were observed on a body weight basis, respectively. BHT-induced cytochrome P-450 cannot be distinguished from phenobarbital (PB)-induced cytochrome in many respects we have examined: i.e. 1) a broad substrate specificity; 2) absence of the blue shift in the CO-binding difference spectrum; 3) no rise in the peak height ratio of ethylisocyanide difference spectrum; 4) absence of alpha-naphthoflavone inhibition of p-nitroanisole demethylase activity; 5) marked increases of 50,000 and 54,000 molecular weight polypeptides in SDS-polyacrylamide gel electrophoresis. However, the induction of 46,000 molecular weight polypeptide by BHT in rats was more conspicuous than that by PB, and this induction was not observed in mice. In contrast to this marked induction, the administration of BHT to MC nonresponsive DBA/2N mice produced neither heptic enlargement nor induction of cytochromes, but did not produce an extremely high mortality.