2-乙酰氨基芴对药物代谢酶诱导作用的表征

Characterization of the induction of drug-metabolizing enzymes by 2-acetylaminofluorene.

作者信息

Aström A, DePierre J W

出版信息

Biochim Biophys Acta. 1981 Mar 18;673(3):225-33. doi: 10.1016/0304-4165(81)90330-5.

Abstract

Changes in hepatic drug-metabolizing enzymes after intraperitoneal treatment of rats with 2-acetylaminofluorene have been investigated. This treatment was found to increase microsomal epoxide hydrolase to 762%, cytochrome P-450 to 143%, NADPH-cytochrome c reductase to 160%, cytochrome b5 to 171%, cytoplasmic DT-diaphorase to 229% and soluble glutathione S-transferase activities to 200-250% of control values. These increases were time- and dose-dependent, being maximal after injection of 50 mg 2-acetylaminofluorene/kg body wt. once daily for 5 days. Enzyme markers for the plasma membrane, mitochondria, lysosomes and the soluble cytoplasm were not affected by treatment with 2-acetylaminofluorene. The present study indicates that this induction is different from that obtained with phenobarbital and 3-methylcholanthrene and more closely resembles that seen with trans-stilbene oxide.

摘要

已对用2-乙酰氨基芴腹腔注射处理大鼠后肝脏药物代谢酶的变化进行了研究。发现这种处理可使微粒体环氧化物水解酶增加至对照值的762%，细胞色素P-450增加至143%，NADPH-细胞色素c还原酶增加至160%，细胞色素b5增加至171%，胞质DT-黄递酶增加至229%，可溶性谷胱甘肽S-转移酶活性增加至对照值的200 - 250%。这些增加具有时间和剂量依赖性，在以50 mg 2-乙酰氨基芴/千克体重每日注射一次、持续5天时达到最大值。质膜、线粒体、溶酶体和可溶性细胞质的酶标志物不受2-乙酰氨基芴处理的影响。本研究表明，这种诱导不同于用苯巴比妥和3-甲基胆蒽所获得的诱导，并且更类似于反式氧化 stilbene所观察到的诱导。