The Role of Ferroptosis in Hepatocyte Injury Induced by α-Amanitin

ObjectiveTo explore whether ferroptosis is involved in α-amanitin-induced hepatocyte injury by detecting iron deposition in mice liver tissues, oxidative stress indicators in hepatocytes and L-02 cells, and expressions of ferroptosis-related proteins after α-amanitin exposure.MethodsThe poisoning mo...

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Main Authors: WANG Hao-wei, ZHANG Xiao-xing, YANG Gen-meng, WANG Shang-wen, ZENG Xiao-feng
Format: Article
Language:zho
Published: Editorial Office of Journal of Forensic Medicine 2025-04-01
Series:Fayixue Zazhi
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Online Access:http://www.fyxzz.cn/CN/10.12116/j.issn.1004-5619.2024.440411
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Summary:ObjectiveTo explore whether ferroptosis is involved in α-amanitin-induced hepatocyte injury by detecting iron deposition in mice liver tissues, oxidative stress indicators in hepatocytes and L-02 cells, and expressions of ferroptosis-related proteins after α-amanitin exposure.MethodsThe poisoning models of α-amanitin C57BL/6J mice and L-02 cell were established. The Lillie ferrous iron staining and Prussian blue staining were used to detect iron deposition; the kits were applied to detect the levels of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione (GSH). Western blotting was performed to analyze expressions of p53, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4).ResultsCompared with the control group, after α-amanitin exposure, positive cell rates of Fe2+ and Fe3+ in mice liver tissues increased significantly. In the liver tissues of medium (0.35 mg/kg) and high (0.45 mg/kg) dose groups and L-02 cells treated with 1 μmol/L α-amanitin, the level of GSH decreased, the level of MDA increased, and the activities of SOD and CAT decreased significantly. In addition, α-amanitin upregulated the expression of p53 in a concentration- and time-dependent manner and inhibited the expressions of SLC7A11 and GPX4.ConclusionFerroptosis plays an important role in α-amanitin-induced hepatocyte injury. Abnormalities of ferroptosis-related indicators can provide references for the forensic identification of α-amanitin poisoning.
ISSN:1004-5619