Nano‐selenium attenuates mitochondrial‐associated apoptosis via the PI3K / AKT pathway in nickel‐induced hepatotoxicity in vivo and in vitro

作者：Caixia Wang, Zhangyu Gu, Xueyan Gu, Xinyue Tan, Shuang Wang, Rui Zhang, Ruifen Li, Mingkun Sun, Chunyan Gui, Sheng Li, Yixing Ye, Jianhua Ma, Li Su, Changhao Liang · 发表于：Environmental Toxicology · 年份：2021 · DOI：10.1002/tox.23381 · 被引用次数：21 · 研究领域：Heavy Metal Exposure and Toxicity、Trace Elements in Health、Selenium in Biological Systems

Abstract The aim of this study was to investigate the protective effects of Nano‐Se against nickel (Ni)‐induced hepatotoxicity and the potential mechanism. Hence, we constructed in vivo and in vitro models of Ni‐induced hepatotoxicity. Sprague–Dawley (SD) rats were exposed to nickel sulfate (NiSO 4 , 5.0 mg/kg, i.p.) with or without Nano‐Se (0.5, 1, and 2 mg/kg, oral gavage) co‐administration for 14 days, and HepG2 cells were exposed to NiSO 4 (1500 μM) with or without Nano‐Se (20 μM) for 24 h. Nano‐Se obviously prevented Ni‐induced hepatotoxicity indicated by ameliorating pathological change and decreasing Ni accumulation in rat livers. Ni induced a significant increase in hepatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSH‐Px), and malondialdehyde (MDA) level, decreased the glutathione (GSH) content while compared to those in the control group. Nano‐Se administration improved the hepatic antioxidant capacity through increase hepatic GSH contents and GSH‐Px activity, decrease the activities of SOD, CAT, and MDA level. Nano‐Se improved the cell viability, decreased active oxygen (ROS) generation and ameliorated morphological changes of nuclear structures in Ni‐treated HepG2 cells. In addition, Nano‐Se inhibited the Ni‐induced increases of cytochrome c, caspase‐9, cleaved caspase‐3, increased PI3K and AKT phosphorylation both in vivo and in vitro. Besides, the PI3K inhibitor Y294002 could inhibit the protective effects of Nano‐Se on apo...