绵羊和牛肝脏微粒体对阿苯达唑的比较性硫氧化作用及甲巯咪唑的抑制作用

Comparative sulphoxidation of albendazole by sheep and cattle liver microsomes and the inhibitory effect of methimazole.

Lanusse C E, Nare B, Prichard R K

Institute of Parasitology, McGill University, Ste-Anne de Bellevue, QC, Canada.

Xenobiotica. 1993 Mar;23(3):285-95. doi: 10.3109/00498259309059382.

Abstract

The comparative rates of oxidation of the benzimidazole anthelmintic, albendazole (ABZ), by sheep and cattle liver microsomes, and inhibition by the antithyroid compound methimazole (MTZ) were investigated. 2. ABZ was oxidized to its sulphoxide metabolite (ABZSO) in an NADPH concentration-dependent reaction. Heat inactivation of the microsomal flavin-containing mono-oxygenase system significantly decreased the NADPH consumption of microsomes in the presence of ABZ, MTZ and thiourea. 3. Oxidation of ABZ, MTZ and thiourea by sheep liver microsomes consumed significantly more NADPH than oxidation by cattle microsomes. 4. Neither the pro-ABZ drug, netobimin, nor the ABZ sulphone metabolite (ABZSO2) was modified by incubation with either sheep or cattle liver microsomes. 5. ABZSO was oxidized into ABZSO2 at a very slow rate and only when a high microsomal protein concentration was used. 6. MTZ was a potent inhibitor of ABZ sulphoxidation and the inhibition was significantly lower in cattle than in sheep microsomes.

摘要

研究了绵羊和牛肝微粒体对苯并咪唑驱虫药阿苯达唑（ABZ）的氧化比较速率，以及抗甲状腺化合物甲巯咪唑（MTZ）对其的抑制作用。2. ABZ在依赖烟酰胺腺嘌呤二核苷酸磷酸（NADPH）浓度的反应中被氧化为其亚砜代谢物（ABZSO）。微粒体含黄素单加氧酶系统的热失活显著降低了在存在ABZ、MTZ和硫脲的情况下微粒体对NADPH的消耗。3. 绵羊肝微粒体对ABZ、MTZ和硫脲的氧化消耗的NADPH比牛微粒体的氧化消耗的显著更多。4. 前体ABZ药物奈托比明和ABZ砜代谢物（ABZSO2）与绵羊或牛肝微粒体孵育后均未发生修饰。5. ABZSO以非常缓慢的速率被氧化为ABZSO2，且仅在使用高微粒体蛋白浓度时才会发生。6. MTZ是ABZ硫氧化的强效抑制剂，且在牛微粒体中的抑制作用明显低于绵羊微粒体。