硝呋替莫和苯硝唑在肝脏微粒体中的硝基还原生物转化的物种和性别差异。

Species and sex differences in the liver microsomal nitroreductive biotransformation of nifurtimox and benznidazole.

作者信息

Aguilar E G, Koldobsky C, de Toranzo E G, Castro J A

出版信息

Arch Int Pharmacodyn Ther. 1987 Jun;287(2):181-7.

Abstract

Nifurtimox (NFX) and Benznidazole (Bz) are two drugs effective against acute Chagas' disease. Both have considerable toxic side effects related to nitroreductive biotransformation. In this work, we studied the species and sex differences in liver microsomal NFX (NFX-ase) and Bz nitroreductase activity (Bz-ase). Animal species tested were rats, mice, hamsters and guinea-pigs. Bz-ase is significantly higher in male rats and hamsters than in females. No significant sex difference was observed in mice or guinea-pigs. Bz-ase in the males is: hamsters greater than mice greater than guinea-pig approximately equal to rat and in females it is: mice approximately equal to guinea-pig approximately equal to hamster greater than rat. NFX-ase is higher in either male rats or female mice than in either female rats or male mice. No sex difference was observed in the other species. In males NFX-ase is: hamsters approximately equal to mice greater than rat approximately equal to guinea-pig, while in females it is mice approximately equal to hamsters greater than guinea-pig approximately equal to rat. Results suggest that hamsters and mice might be the most suitable species to study toxic effects related to their liver microsomal nitroreductive biotransformation. This might be of particular relevance for carcinogenicity studies.

摘要

硝呋替莫（NFX）和苯硝唑（Bz）是两种对急性恰加斯病有效的药物。两者都有与硝基还原生物转化相关的相当大的毒副作用。在这项研究中，我们研究了肝脏微粒体中NFX（NFX酶）和Bz硝基还原酶活性（Bz酶）的物种和性别差异。所测试的动物物种有大鼠、小鼠、仓鼠和豚鼠。雄性大鼠和仓鼠的Bz酶活性显著高于雌性。在小鼠或豚鼠中未观察到显著的性别差异。雄性的Bz酶活性为：仓鼠＞小鼠＞豚鼠≈大鼠，雌性为：小鼠≈豚鼠≈仓鼠＞大鼠。雄性大鼠或雌性小鼠的NFX酶活性高于雌性大鼠或雄性小鼠。在其他物种中未观察到性别差异。雄性的NFX酶活性为：仓鼠≈小鼠＞大鼠≈豚鼠，而雌性为：小鼠≈仓鼠＞豚鼠≈大鼠。结果表明，仓鼠和小鼠可能是研究与其肝脏微粒体硝基还原生物转化相关的毒性作用最合适的物种。这可能对致癌性研究特别重要。