Abstract:
Objective To explore the effects of cobalt chloride exposure on the indicators of oxidative damage and ferroptosis in the liver of mice.
Methods A total of 24 male C57BL/6 specific pathogen free(SPF) grade mice were randomly divided into three exposure groups and one control group to receive intraperitoneal injection of cobalt chloride solution at doses of 4, 8, and 12 mg/kg and an equal volume of saline, respectively, once daily, for a total of 30 days. Then the mice were sacrificed to obtain the liver to calculate the organ coefficient. The liver homogenate supernatant was prepared to determine the content of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and oxidized glutathione (GSSG) by kits. Western blot was performed to measure the protein expression levels of glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1) and long-chain acyl coenzyme A synthetase 4 (ACSL4) in the liver tissue.
Results Compared with that of the control group, the liver coefficient was significantly increased in the 4 mg/kg exposure group (F=6.15, P=0.027). The content of SOD was significantly decreased in the 12 mg/kg exposure group than in the control group (F=6.56, P=0.028). As the dose of cobalt chloride increased, the content of MDA was significantly increased (F=30.93, P < 0.001), the GSH content and GSH/GSSG ratio were significantly decreased (F=22.78, 24.57, both P < 0.01), the levels of GPX4 and FSP1 were significantly decreased (F=41.47, 19.397, both P < 0.01), and the level of ACSL4 was significantly increased (F=16.01, P=0.004).
Conclusion Cobalt chloride exposure can cause hepatic oxidative damage in mice, and promote hepatic ferroptosis by downregulating GPX4 and FSP1 and upregulating ACSL4.