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Hence, we constructed in vivo and in vitro models of Ni\u2010induced hepatotoxicity. Sprague\u2013Dawley (SD) rats were exposed to nickel sulfate (NiSO<jats:sub>4<\/jats:sub>, 5.0\u00a0mg\/kg, i.p.) with or without Nano\u2010Se (0.5, 1, and 2\u00a0mg\/kg, oral gavage) co\u2010administration for 14\u2009days, and HepG2 cells were exposed to NiSO<jats:sub>4<\/jats:sub> (1500\u2009\u03bcM) with or without Nano\u2010Se (20\u2009\u03bcM) for 24\u2009h. Nano\u2010Se obviously prevented Ni\u2010induced 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\u2010Px), and malondialdehyde (MDA) level, decreased the glutathione (GSH) content while compared to those in the control group. Nano\u2010Se administration improved the hepatic antioxidant capacity through increase hepatic GSH contents and GSH\u2010Px activity, decrease the activities of SOD, CAT, and MDA level. Nano\u2010Se improved the cell viability, decreased active oxygen (ROS) generation and ameliorated morphological changes of nuclear structures in Ni\u2010treated HepG2 cells. In addition, Nano\u2010Se inhibited the Ni\u2010induced increases of cytochrome c, caspase\u20109, cleaved caspase\u20103, increased PI3K and AKT phosphorylation both in vivo and in vitro. Besides, the PI3K inhibitor Y294002 could inhibit the protective effects of Nano\u2010Se on apoptosis. Thus, Nano\u2010Se significantly activates PI3K\/AKT signaling to ameliorate apoptosis in Ni\u2010induced hepatotoxicity.<\/jats:p>","DOI":"10.1002\/tox.23381","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T17:45:39Z","timestamp":1633715139000},"page":"101-119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Nano\u2010selenium attenuates mitochondrial\u2010associated apoptosis via the <scp>PI3K<\/scp>\/<scp>AKT<\/scp> pathway in nickel\u2010induced hepatotoxicity in vivo and in vitro"],"prefix":"10.1002","volume":"37","author":[{"given":"Caixia","family":"Wang","sequence":"first","affiliation":[{"name":"School of Public Health Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangyu","family":"Gu","sequence":"additional","affiliation":[{"name":"Henan Institute of Advanced Technology Zhengzhou University  Zhengzhou 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