Mechanism of ferroptosis in mice liver induced by cadmium exposure
Cadmium(Cd)is an important environmental toxicant that can cause serious damage to various organs including severe hepatotoxicity in intoxicated animals.The purpose of this study is to reveal the role and mechanism of Cd exposure on ferroptosis in mice liver.Twenty-four 8-week-old ICR mice were randomly divided into the control group and 3 cadmium exposure groups(group Cd).Mice in the Cd group were injected with CdCl2 of 1,2 and 3 mg/kg intraperitoneally every day,while the control group was injected with the same volume of saline for 7 days.All mice were killed on the 8 th day,and the histopathological and ultra-pathological changes of liver were observed.The activity of liver functional enzymes(ALT,AST)in serum,the contents of malondial-dehyde(MDA),glutathione peroxidase(GSH-Px)and Cd in liver and the protein expression levels of ferroptosis related factors were detected.The results showed that interstitial congestion of liver,loss of hepatocyte cords,flocculent dense substance in mitochondria and matrix degeneration ridge were observed in liver of the CdCl2 treatment mice.The results showed that serum levels of ALT and AST,the contents of MDA and Cd in liver were increased significantly,while the activity of GSH-Px in liver was significantly decreased(P＜0.01)in CdCl2 exposed mice.Protein levels of GPX4,SLC7A11,FTH1 and FTL were decreased significantly,but protein levels of ACSL4 and HO-1 were significantly increased in CdCl2 exposed mice.Thereby,Cd exposure caused disruption of iron metabolism in mice liver,decreased antioxidant levels and lipid peroxidation in ICR mice,mediating the occurrence of liver ferroptosis.This study provides an important theoretical data for further improving the hepatotoxicity mechanism of Cd exposure.
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