Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Biol Trace Elem Res. 2022 Mar;200(3):1190-1200. doi: 10.1007/s12011-021-02712-3. Epub 2021 Apr 17.
Arsenic as a heavy metal and toxic pollutant has been established that has the hepatotoxic effect in animal and human models. Previous studies showed that mitochondria as the first target of arsenic toxicity has a pathogenic role in liver diseases. This study investigated alpha lipoic acid (ALA) as an antioxidant could ameliorate against liver toxicity induced by arsenic in rat mitochondria. First, mitochondria were isolated by the liver tissue centrifugation protocol. Then, isolated mitochondria were exposed with different concentrations of ALA and arsenic in different times for receiving the optimum dose and time. Finally, mitochondria were pretreated with the optimum concentrations and times of ALA and then treated with optimum concentration and time of arsenic (160 μg/ml; 30 min). The results demonstrated a significant decrease in total mitochondrial dehydrogenase activity (mitochondrial complex II) by 3, 4 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay after arsenic exposure. Mitochondria treated with arsenic also showed a significant increase in ROS generation, MMP, and MDA levels. The activity of mitochondrial catalase and mitochondrial GSH significantly decreased after exposure of mitochondria with arsenic. Pretreatment of mitochondria with ALA improved mitochondrial complex II activity; decreased mitochondrial membrane damage, MDA, and ROS amounts; and ameliorated mitochondrial GSH levels and mitochondrial catalase activity. These findings revealed that arsenic induced oxidative stress and mitochondria dysfunction, while ALA improved mitochondrial function through increasing of antioxidant defense or preserving of complex II, but suggested that ALA could prevent from mitochondria dysfunction.
砷作为一种重金属和有毒污染物，已被证实对动物和人类模型具有肝毒性作用。先前的研究表明，线粒体作为砷毒性的第一个靶点，在肝脏疾病中具有发病作用。本研究探讨了作为抗氧化剂的α-硫辛酸 (ALA) 是否能减轻大鼠线粒体砷毒性。首先，通过肝组织离心方案分离线粒体。然后，将分离的线粒体暴露于不同浓度的 ALA 和砷中不同时间，以获得最佳剂量和时间。最后，用最佳浓度和时间的 ALA 预处理线粒体，然后用最佳浓度和时间的砷（160μg/ml；30 分钟）处理。结果表明，砷暴露后，3,4 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定法测定的总线粒体脱氢酶活性（线粒体复合物 II）显著下降。用砷处理的线粒体也显示 ROS 生成、MMP 和 MDA 水平显著增加。线粒体中砷暴露后，线粒体过氧化氢酶和线粒体 GSH 的活性显著降低。用 ALA 预处理线粒体可改善线粒体复合物 II 活性；减少线粒体膜损伤、MDA 和 ROS 含量；并改善线粒体 GSH 水平和线粒体过氧化氢酶活性。这些发现表明，砷诱导氧化应激和线粒体功能障碍，而 ALA 通过增加抗氧化防御或保护复合物 II 来改善线粒体功能，但表明 ALA 可以防止线粒体功能障碍。
