硝基杂环药物对大鼠肝脏提取物中脂质过氧化和谷胱甘肽含量的影响。
Effect of nitroheterocyclic drugs on lipid peroxidation and glutathione content in rat liver extracts.
作者信息
Dubin M, Goijman S G, Stoppani A O
出版信息
Biochem Pharmacol. 1984 Nov 1;33(21):3419-23. doi: 10.1016/0006-2952(84)90114-x.
Incubation of rat liver cell-free extracts with an NADPH-generating system and with nifurtimox or benznidazole (two nitroheterocyclic drugs used in the treatment of Chagas' disease) produced oxidation of reduced glutathione (GSH) and increased lipid peroxidation, as shown by the generation of thiobarbituric-acid-reacting intermediates. Nifurtimox and benznidazole inhibited GSSG-reductase, but not GSH-peroxidase, the former inhibition contributing to GSH depletion. In every case, nifurtimox was more effective than benznidazole. Addition of GSH or free-radical scavengers (catalase, superoxide dismutase, mannitol, sodium benzoate or L-histidine) prevented the effect of nifurtimox on lipid peroxidation reactions. These results support the assumption [M. Dubin, S. N. J. Moreno, E. E. Martino, R. Docampo and A. O. M. Dubin, Biochem. Pharmac. 32, 483 (1983)] that, in the rat liver, GSH exerts a protective action against oxygen radicals generated by the nitroheterocyclic drugs.
将大鼠肝细胞游离提取物与一个能产生NADPH的系统以及硝呋替莫或苯硝唑（两种用于治疗恰加斯病的硝基杂环药物）一起孵育，会导致还原型谷胱甘肽（GSH）氧化并增加脂质过氧化，硫代巴比妥酸反应性中间体的生成就表明了这一点。硝呋替莫和苯硝唑抑制谷胱甘肽二硫化物还原酶，但不抑制谷胱甘肽过氧化物酶，前者的抑制作用导致了GSH耗竭。在每种情况下，硝呋替莫都比苯硝唑更有效。添加GSH或自由基清除剂（过氧化氢酶、超氧化物歧化酶、甘露醇、苯甲酸钠或L-组氨酸）可防止硝呋替莫对脂质过氧化反应的影响。这些结果支持了这样一种假设[M. 杜宾、S. N. J. 莫雷诺、E. E. 马蒂诺、R. 多坎波和A. O. M. 杜宾，《生物化学与药物学》32卷，483页（1983年）]，即在大鼠肝脏中，GSH对硝基杂环药物产生的氧自由基具有保护作用。
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