Heidari Reza, Babaei Hossein, Eghbal Mohammad Ali
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Arh Hig Rada Toksikol. 2013 Jun;64(2):15-24. doi: 10.2478/10004-1254-64-2013-2297.
Isoniazid is one of the most commonly used drugs to treat tuberculosis. Its administration is associated with a high incidence of hepatotoxicity. The aim of this study was to establish the protective effects of taurine against cytotoxicity induced by isoniazid and its suspected toxic metabolite hydrazine in isolated rat hepatocytes by measuring reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial depolarisation, reduced glutathione (GSH), and oxidised glutathione (GSSG). Isoniazid caused no significant ROS formation in normal hepatocytes, but in glutathione-depleted cells it was considerable. Hydrazine caused ROS formation and lipid peroxidation in both intact and glutathione-depleted cells. Both isoniazid and hydrazine caused mitochondrial membrane depolarisation. Hydrazine lowered cellular GSH reserve and increased GSSG. Taurine (200 μmol L(-1)) and N-acetylcysteine (200 μmol L(-1)) effectively countered the toxic effects of isoniazid and/or hydrazine by decreasing ROS formation, lipid peroxidation, and mitochondrial damage. Taurine prevented depletion of GSH and lowered GSSG levels in hydrazine-treated cells. This study suggests that the protective effects of taurine against isoniazid and its intermediary metabolite hydrazine cytotoxicity in rat hepatocytes could be attributed to antioxidative action.
异烟肼是治疗结核病最常用的药物之一。其给药与高肝毒性发生率相关。本研究的目的是通过测量活性氧（ROS）形成、脂质过氧化、线粒体去极化、还原型谷胱甘肽（GSH）和氧化型谷胱甘肽（GSSG），确定牛磺酸对异烟肼及其疑似有毒代谢物肼在分离的大鼠肝细胞中诱导的细胞毒性的保护作用。异烟肼在正常肝细胞中未引起显著的ROS形成，但在谷胱甘肽耗尽的细胞中ROS形成相当可观。肼在完整细胞和谷胱甘肽耗尽的细胞中均引起ROS形成和脂质过氧化。异烟肼和肼均引起线粒体膜去极化。肼降低细胞内GSH储备并增加GSSG。牛磺酸（200μmol L⁻¹）和N-乙酰半胱氨酸（200μmol L⁻¹）通过减少ROS形成、脂质过氧化和线粒体损伤有效对抗异烟肼和/或肼的毒性作用。牛磺酸可防止肼处理细胞中GSH的消耗并降低GSSG水平。本研究表明，牛磺酸对大鼠肝细胞中异烟肼及其中间代谢物肼细胞毒性的保护作用可能归因于抗氧化作用。
