CYTOPROTECTIVE EFFECTS OF TAURINE AGAINST TOXICITY INDUCED BY ISONIAZID AND HYDRAZINE IN ISOLATED RAT HEPATOCYTES
CYTOPROTECTIVE EFFECTS OF TAURINE AGAINST TOXICITY INDUCED BY ISONIAZID AND HYDRAZINE IN ISOLATED RAT HEPATOCYTES
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DOI：
10.2478/10004-1254-64-2013-2297
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发表时间：
2013-06-01
影响因子：
2.1
通讯作者：
Eghbal, Mohammad Ali
中科院分区：
文献类型：
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作者：
Heidari, Reza;Babaei, Hossein;Eghbal, Mohammad Ali
异烟肼是治疗结核病最常用的药物之一。其给药与肝毒性的高发生率相关。本研究的目的是建立牛磺酸对异烟肼及其可疑毒性代谢物肼诱导的细胞毒性的保护作用，通过测量活性氧（ROS）的形成，脂质过氧化，线粒体去极化，还原型谷胱甘肽（GSH），氧化型谷胱甘肽（GSSG）在离体大鼠肝细胞。异烟肼在正常肝细胞中不会引起显着的活性氧形成，但在谷胱甘肽耗尽的细胞中，活性氧形成相当大。肼引起的ROS形成和脂质过氧化反应，在完整的和谷胱甘肽耗尽的细胞。异烟肼和肼引起线粒体膜去极化。肼降低细胞GSH储备，增加GSSG。牛磺酸（200 μ mol L-1）和N-乙酰半胱氨酸（200 μ mol L-1）通过减少ROS形成、脂质过氧化和线粒体损伤，有效地对抗了异烟肼和/或肼的毒性作用。牛磺酸可防止GSH耗竭，并降低肼处理细胞中的GSSG水平。本研究提示牛磺酸对异烟肼及其中间代谢产物肼的肝细胞毒性的保护作用可能与抗氧化作用有关。
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 mu mol L-1) and N-acetylcysteine (200 mu mol 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.