Tekwani B L, Tripathi L M, Mukerjee S, Gupta S, Pandey V C, Katiyar J C, Ghatak S, Shukla O P
Central Drug Research Institute, Lucknow, India.
Exp Mol Pathol. 1990 Jun;52(3):330-9. doi: 10.1016/0014-4800(90)90073-m.
Experimental infection of golden hamsters with the hookworm, Ancylostoma ceylanicum, caused a profound decline in the hepatic microsomal cytochrome P450 content. Concomitant decrease was also noticed in aminopyrine N-demethylase and benzo[a]pyrene hydroxylase activities. However, aniline hydroxylase activity was only marginally elevated during the infection. Microsomal markers, viz., cytochrome b5, NADH-cytochrome-c reductase, and glucose-6-phosphatase, were not significantly altered. Hepatic tissue exhibited an accumulation of lipids, especially phospholipids, triglycerides, and cholesterol, resulting in fatty necrosis around the central vein region. Isolated hepatic microsomes showed a decrease in phosphatidylcholine content. Impairment in hepatic mixed function oxidase (MFO) activities was further confirmed by prolongation in hexobarbital sleeping time and zoxazolamine-induced paralysis. The hepatic MFO system of A. ceylanicum-infected hamsters responded qualitatively and quantitatively in a manner similar to that of control hamsters, upon stimulation with selective chemical inducers like phenobarbitone and 3-methylcholanthrene. Kinetic and in vitro substrate binding studies revealed that for aminopyrine the substrate affinity and the maximum enzyme activity (Vmax) were decreased, while for aniline the binding affinity was decreased and the binding capacity was enhanced. Results indicate specific/selective impairment of the hepatic microsomal cytochrome P450 system during hookworm infection and may have many practical implications in toxicology and pharmacology.
用锡兰钩虫对金黄仓鼠进行实验性感染，导致肝脏微粒体细胞色素P450含量大幅下降。氨基比林N-脱甲基酶和苯并[a]芘羟化酶活性也随之降低。然而，感染期间苯胺羟化酶活性仅略有升高。微粒体标志物，即细胞色素b5、NADH-细胞色素c还原酶和葡萄糖-6-磷酸酶，没有显著变化。肝组织出现脂质蓄积，尤其是磷脂、甘油三酯和胆固醇，导致中央静脉区域周围出现脂肪坏死。分离的肝微粒体显示磷脂酰胆碱含量降低。己巴比妥睡眠时间延长和唑沙宗诱导的麻痹进一步证实了肝脏混合功能氧化酶（MFO）活性受损。在用苯巴比妥和3-甲基胆蒽等选择性化学诱导剂刺激后，感染锡兰钩虫的仓鼠的肝脏MFO系统在定性和定量方面的反应与对照仓鼠相似。动力学和体外底物结合研究表明，对于氨基比林，底物亲和力和最大酶活性（Vmax）降低，而对于苯胺，结合亲和力降低，结合能力增强。结果表明，钩虫感染期间肝脏微粒体细胞色素P450系统存在特异性/选择性损伤，这可能在毒理学和药理学中有许多实际意义。
