Guo Hongrui, Yin Heng, Zuo Zhicai, Yang Zhuangzhi, Yang Yue, Wei Ling, Cui Hengmin, Deng Huidan, Chen Xia, Chen Jian, Zhu Yanqiu, Ouyang Ping, Geng Yi, Du Zongjun, Tang Huaqiao, Wang Fengyuan, Fang Jing
College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China; Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu 611130, China.
College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China.
Ecotoxicol Environ Saf. 2021 Nov 2;228:112954. doi: 10.1016/j.ecoenv.2021.112954.
As an extensively environmental pollution, Nickel (Ni) represents a serious hazard to human health. The present study focused on exploring the mechanism of Ni-mediated nephrotoxicity, such as apoptosis, autophagy and oxidative stress. In the current work, NiCl treatment could induce kidney damage. Meanwhile, NiCl treatment elevated ROS production and MDA content and suppressed the antioxidant activity, which was characterized by reducing T-AOC, CAT, SOD activity and GSH content. For investigating the role of oxidative stress on NiCl-mediated nephrotoxicity, N-acetyl cysteine (NAC, effective antioxidant and free radical scavenger) was co-treated with NiCl. The results showed that NAC significantly suppressed the NiCl-mediated oxidative stress and mitigated NiCl-induced the kidney damage. Then, whether oxidative stress-induced autophagy and apoptosis were involved in NiCl-induced nephrotoxicity was explored. The findings demonstrated that NAC relieved NiCl-induced autophagy and reversed the activation of Akt/AMPK/mTOR pathway. Concurrently, the results indicated that NAC attenuated NiCl-induced apoptosis, as evidenced by reduction of apoptotic cells and cleaved-caspase-3/- 8/- 9 together with cleaved-PARP protein levels. To sum up, our findings suggested that NiCl-mediated renal injury was associated with oxidative stress-induced apoptosis and autophagy. This study provides new theoretical basis for excess Ni exposure nephrotoxic researches.
作为一种广泛存在的环境污染物质，镍（Ni）对人类健康构成严重危害。本研究聚焦于探索镍介导的肾毒性机制，如细胞凋亡、自噬和氧化应激。在当前工作中，氯化镍处理可诱导肾脏损伤。同时，氯化镍处理提高了活性氧的产生和丙二醛含量，并抑制了抗氧化活性，其表现为总抗氧化能力、过氧化氢酶、超氧化物歧化酶活性和谷胱甘肽含量降低。为研究氧化应激在氯化镍介导的肾毒性中的作用，将N-乙酰半胱氨酸（NAC，有效的抗氧化剂和自由基清除剂）与氯化镍共同处理。结果表明，NAC显著抑制了氯化镍介导的氧化应激，并减轻了氯化镍诱导的肾脏损伤。然后，探讨了氧化应激诱导的自噬和凋亡是否参与了氯化镍诱导的肾毒性。研究结果表明，NAC减轻了氯化镍诱导的自噬，并逆转了Akt/AMPK/mTOR信号通路的激活。同时，结果表明NAC减轻了氯化镍诱导的凋亡，表现为凋亡细胞减少，以及半胱天冬酶-3/-8/-9和聚（ADP-核糖）聚合酶蛋白裂解水平降低。综上所述，我们的研究结果表明，氯化镍介导的肾损伤与氧化应激诱导的凋亡和自噬有关。本研究为过量镍暴露肾毒性研究提供了新的理论依据。
