Autor: |
Wang, Caixia1 (AUTHOR), Gu, Zhangyu2,3 (AUTHOR), Gu, Xueyan1 (AUTHOR), Tan, Xinyue1 (AUTHOR), Wang, Shuang1 (AUTHOR), Zhang, Rui1 (AUTHOR), Li, Ruifen1 (AUTHOR), Sun, Mingkun1 (AUTHOR), Gui, Chunyan1 (AUTHOR), Li, Sheng4 (AUTHOR), Ye, Yixing3 (AUTHOR), Ma, Jianhua1 (AUTHOR), Su, Li1,5 (AUTHOR) sul@lzu.edu.cn, Liang, Changhao3 (AUTHOR) chliang@issp.ac.cn |
Předmět: |
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Zdroj: |
Environmental Toxicology. Jan2022, Vol. 37 Issue 1, p101-119. 19p. |
Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
Databáze: |
GreenFILE |
Externí odkaz: |
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