Nano‐selenium attenuates mitochondrial‐associated apoptosis via the PI3K / AKT pathway in nickel‐induced hepatotoxicity in vivo and in vitro
| Autor: | Xinyue Tan, Chunyan Gui, Caixia Wang, Rui Zhang, Shuang Wang, Sheng Li, Zhangyu Gu, Jianhua Ma, Yixing Ye, Changhao Liang, Mingkun Sun, Li Su, Xueyan Gu, Ruifen Li |
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| Rok vydání: | 2021 |
| Předmět: |
Health
Toxicology and Mutagenesis Glutathione reductase Apoptosis Management Monitoring Policy and Law Pharmacology Toxicology Antioxidants Rats Sprague-Dawley Superoxide dismutase Phosphatidylinositol 3-Kinases Selenium chemistry.chemical_compound Nickel In vivo Animals Protein kinase B PI3K/AKT/mTOR pathway biology Chemistry Cytochrome c technology industry and agriculture General Medicine Glutathione Rats Oxidative Stress biology.protein Chemical and Drug Induced Liver Injury Proto-Oncogene Proteins c-akt |
| Zdroj: | Environmental Toxicology. 37:101-119 |
| ISSN: | 1522-7278 1520-4081 |
| DOI: | 10.1002/tox.23381 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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