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Alpha lipoic acid attenuates cadmium-induced nephrotoxicity via the mitochondrial apoptotic pathways in rat
Journal of Inorganic Biochemistry ( IF 3.8 ) Pub Date : 2018-04-07
Shihao Chen, Gang Liu, Mengfei Long, Hui Zou, Hengmi Cui

Alpha lipoic acid (α-LA), a potent antioxidant, is protective against acute nephrotoxicity. In the present study, the attenuation of cadmium (Cd)-induced kidney injury by α-LA on was investigated in a rat model. Exposure to 50 mg/L Cd for 12 weeks increased kidney index and Cd content, malondialdehyde (MDA) levels, and histological damage to the renal cortex, and decreased the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Treatment with 50 mg/L Cd also damaged renal cell mitochondria and nuclei, and activated the mitochondrial apoptosis pathway, indicated by increased gene and protein expression/activation of caspase-9, caspase-3, poly ADP-ribose polymerase (PARP) and Bcl-2 adenovirus E1a nineteen kilodalton interacting protein 3 (BNIP3), and translocation of cytochrome c (cyt c), apoptosis-inducing factor (AIF), and endonuclease G (Endo G). However, simultaneous supplementation with α-LA (50 mg/kg·bw) protected kidney cells from Cd-induced cytotoxicity by reducing MDA levels and Cd content, restoring endogenous enzyme activities, renewing mitochondrial function, and preventing activation of the mitochondria apoptosis pathway.



中文翻译:

α硫辛酸通过大鼠线粒体凋亡途径减轻镉诱导的肾毒性

硫辛酸(α-LA)是一种有效的抗氧化剂,可防止急性肾毒性。在本研究中,在大鼠模型中研究了α-LA对镉(Cd)诱导的肾脏损伤的缓解作用。暴露于50 mg / L Cd中12周会增加肾脏指数和Cd含量,丙二醛(MDA)水平以及对肾皮质的组织学损害,并降低谷胱甘肽过氧化物酶(GSH-Px),超氧化物歧化酶(SOD)的活性,过氧化氢酶(CAT)和谷胱甘肽(GSH)。用50 mg / L的镉处理也会破坏肾细胞线粒体和细胞核,并激活线粒体凋亡途径,这表明caspase-9,caspase-3,poly ADP-核糖聚合酶(PARP)和Bcl的基因和蛋白质表达/激​​活增加-2腺病毒E1a十九道尔顿相互作用蛋白3(BNIP3)和细胞色素易位c(cyt c),凋亡诱导因子(AIF)和核酸内切酶G(Endo G)。然而,同时补充α-LA(50 mg / kg·bw)可通过降低MDA水平和Cd含量,恢复内源酶活性,更新线粒体功能并阻止线粒体凋亡途径的活化来保护肾脏细胞免受Cd诱导的细胞毒性。

更新日期:2018-04-08
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