Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significanly correlated with cytochrome P450 suppression

摘要

AIM:To investigate the hepatoprotective activity of tea polyphenols(TP)and its relation with cytochrome P450(CYP450)expression in mice. METHODS:Hepatic CYP450 and CYPb5 levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP(25,50 and 100 mg/kg per day). Then the mice were intragastricly pre-treated with TP (100,200 and 400 mg/kg per day)for six days before paracetamol(1000 mg/kg)was given.Their acute mortality was compared with that of control mice. The mice were pre-treated with TP(100,200,and 400 mg/kg per day)for five days before paracetamol (500 mg/kg)was given.Hepatic CYP2E1 and CYP1A2 protein and mRNA expression levels were evaluated by Western blotting,immunohistochemical staining and transcriptase-polymerase chain reaction. RESULTS:The hepatic CYP450 and CYPb5 levels in mice of TP-treated groups(100,200 and 400 mg/kg per day)were decreased in a dose-dependent manner compared with those in the negative control mice.TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice.Furthermore,TP reduced CYP2E1 and CYP1A2 expression at both protein and mRNA levels in a dose-dependent manner.