Role of ferroptosis in acute cadmium-induced liver injury in mice

Objective To investigate the role of ferroptosis in acute liver injury induced by cadmium (Cd) exposure in mice.

Methods Healthy and clean male ICR mice of 8-10 weeks were randomly divided into control group, and Cd exposure group. The mice in the Cd exposure group were injected with an equal amount of CdCl₂ (4 mg·kg^-1) intraperitoneally. Liver tissues and blood were collected after Cd treatment for 6h, 12h and 24h, respectively. The mice in the control group were injected with normal saline in the same way. The hematoxylineosin (HE) staining method was used to observe the pathological injury of liver. The contents of ALT, AST, total iron, GSH, SOD, H₂O₂ and MDA in serum were detected by corresponding kits. The expression of key genes of ferroptosis in liver tissues of mice were detected by real-time fluorescence quantitative PCR (RT-qPCR) and western blotting.

Results The acute Cd exposure reduced liver weight and organ coefficient in mice, and significantly caused liver function and pathological damage. Compared with the control group, the contents of GSH and SOD in the Cd exposure group were decreased, the contents of ALT, AST, and MDA were increased, and the content of H₂O₂ was significantly increased (P < 0.05). In addition, Cd significantly increased the total iron content in liver of mice, induced the protein expression of HO-1 and FTH1 in liver tissue of mice, while the protein expression of GPX4 was significantly decreased in the Cd exposure group (P < 0.05).

Conclusion Acute Cd exposure can cause oxidative stress, increase iron content, and alter transcription and protein expression of genes associated with ferroptosis in the liver, suggesting that ferroptosis may be involved in liver injury induced by acute Cd exposure.