Comparison of liver injury induced by Perfluorooctanoic Acid in mice of different exposure models

• 1、School of Food Science and Technology, Jiangnan University, Wuxi, 214122

Abstract：Objective: To investigate the liver damage in mice caused by perfluorooctanPFOAoic acid with different doses/time span. Methods: C57BL/6J male mice were exposed to PFOA with subacute way (14 days, 0 mg/kg BW, 3 mg/kg BW, 30 mg/kg BW) and chronic way (30 days, 0 mg/kg BW, 2.5 mg/kg BW, 5 mg/kg BW, 10 mg/kgBW). The body weight and the changes of various organs weight (liver, kidney, spleen) of each mice were measured. The content of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (γ-GT) in serum, and oxidative stress levels [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) activity and malondialdehyde (MDA) content] in liver homogenates were also investigated. Histopathological changes of the liver were evaluated. Results: In the subacute model, the liver/body ratio increased and the spleen/body ratio decreased significantly in the mice exposed to PFOA, with a dose-dependent manner. Content of ALT and ALP in serum increased significantly, but AST and γ-GT not. In the liver homogenate, the activity of SOD and GSH were inhibited significantly, and the level of MDA also decreased obviously. Hepatocyte hypertrophy was observed in the subacute 3 mg/kg BW and 30 mg/kg BW groups, and hepatic focal necrosis was observed in some livers in a dose-dependent manner. In the chronic model, body weight decreased in a dose-dependent manner after 30th day of PFOA exposure, and the liver/body ratio of the mice exposed to PFOA elevated significantly. The spleen/body ratio showed a significant decrease in the group exposed to highest dose (10 mg/kg BW) of PFOA. The activities of SOD, GSH and CAT in liver homogenate were inhibited significantly, and contents of serum ALT and ALP increased obviously. In the chronic high, medium and low dose exposure groups, hepatic hypertrophy was found in the central lobe of the lobules, and hepatocyte necrosis was also observed in some livers in a dose-dependent manner. Conclusion: PFOA exposure in different manner inhibited the body weight gain of C57BL/6J mice and even caused weight loss, resulting in liver enlargement and spleen atrophy in mice. Spleen atrophy is more pronounced in the subacute toxicity model. The changes of liver oxidative stress and serum transaminase levels were more obvious in the chronic toxicity model.

Keywords： PFOA exposure subacute toxicity model chronic toxicity model liver toxicity