The Role of Ferroptosis in Hepatocyte Injury Induced by α-Amanitin
10.12116/j.issn.1004-5619.2024.440411
- VernacularTitle:铁死亡在α-鹅膏毒肽诱导肝细胞损伤中的作用
- Author:
Hao-Wei WANG
1
;
Xiao-Xing ZHANG
;
Gen-Meng YANG
;
Shang-Wen WANG
;
Xiao-Feng ZENG
Author Information
1. 昆明医科大学法医学院,云南 昆明 650500
- Keywords:
forensic pathology;
forensic toxicology;
α-amanitin;
ferroptosis;
oxidative stress;
hepatic in-jury;
L-02 cell;
mice
- From:
Journal of Forensic Medicine
2025;41(2):152-159
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore whether ferroptosis is involved in α-amanitin-induced hepatocyte in-jury 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.Methods The poi-soning 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).Results Compared 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.Con-clusion Ferroptosis 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.