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 (NiSO₄, 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 NiSO₄ (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 apoptosis. Thus, Nano-Se significantly activates PI3K/AKT signaling to ameliorate apoptosis in Ni-induced hepatotoxicity.

中文翻译：

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纳米硒通过 PI3K/AKT 通路在镍诱导的体内和体外肝毒性中减弱线粒体相关细胞凋亡

本研究的目的是研究纳米硒对镍 (Ni) 诱导的肝毒性的保护作用及其潜在机制。因此，我们构建了 Ni 诱导的肝毒性的体内和体外模型。Sprague-Dawley (SD) 大鼠暴露于硫酸镍 (NiSO ₄ , 5.0 mg/kg, ip) 与或不与 Nano-Se (0.5, 1, 和 2 mg/kg, 口服管饲) 共同给药 14 天，和 HepG2 细胞暴露于 NiSO ₄(1500 μM) 有或没有 Nano-Se (20 μM) 24 小时。纳米硒通过改善大鼠肝脏的病理变化和减少镍的积累，明显地防止了镍诱导的肝毒性。与对照组相比，Ni诱导肝脏超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽还原酶（GSH-Px）和丙二醛（MDA）水平的活性显着增加，谷胱甘肽（GSH）含量降低. 纳米硒给药通过增加肝脏 GSH 含量和 GSH-Px 活性，降低 SOD、CAT 和 MDA 水平的活性来改善肝脏抗氧化能力。Nano-Se 提高了细胞活力，减少了活性氧 (ROS) 的产生并改善了 Ni 处理的 HepG2 细胞核结构的形态变化。此外，Nano-Se 在体内和体外抑制 Ni 诱导的细胞色素 c、caspase-9、裂解的 caspase-3 增加，增加 PI3K 和 AKT 磷酸化。此外，PI3K抑制剂Y294002可以抑制Nano-Se对细胞凋亡的保护作用。因此，Nano-Se 显着激活 PI3K/AKT 信号传导以改善 Ni 诱导的肝毒性中的细胞凋亡。