Acetaminophen induced gender-dependent liver injury and the involvement of GCL and GPx

Abstract

Acetaminophen (AP) is widely used as the antipyretic and analgesic drug in clinic, and it can induce serious liver injury in the case of excessive abuse. The present study showed that AP (400 mg/kg) induced obvious liver injury, while in male mice the hepatotoxicity induced by AP was much more serious than in female mice as indicated by the results of alanine aminotransferase (ALT) activity and reduced glutathione (GSH) amount. Further, the enzymatic activity and protein expression of glutamate-cysteine ligase (GCL) and glutathione peroxidase (GPx) were all higher in female mice liver than in male after the administration of AP (200 mg/kg). Meanwhile, AP (10 mM) decreased GCL and GPx activity in isolated mouse hepatocytes in the time-dependent manner, while the inhibitors of GCL and GPx can augment AP induced-cytotoxicity. Taken together, our results demonstrate the gender-related liver injury induced by AP and the important role of GCL and GPx in regulating such hepatotoxicity.