Mice were pretreated with OC (300, 200 or 100 mg路kg鈭?, body weight) or N-acetyl-L-cysteine (NAC) (300 mg路kg鈭?, body weight) for 3 times at 24 h intervals. APAP was administered 2 h after OC last dose. Chang liver cells were incubated with the medium containing OC (50, 100, 200 mg路mL鈭?) or NAC (10 mmol路L鈭?) with the presence or absence of APAP (10 mmol路L鈭?) for 24 h.
OC showed remarkable hepatoprotective effect 12 h after APAP administration by decreased aspartate aminotransferase and alanine aminotransferase levels, reduced the products of lipid peroxidation, improved the activity of catalase, superoxide dismutase and glutathione peroxidase, inhibited the caspase-3 cleavage and hypoxia inducible factor-1伪 accumulation in vivo. In vitro, OC significantly decreased the activities of metabolism enzyme cytochrome P450 2E1 (CYP2E1) and cyclooxygenase-2 (COX-2) induced by APAP.
OC possesses the ability to protect hepatocyte from APAP-induced liver damage, suggesting that the hepatoprotective mechanism of OC might be related to antioxidation via blocking the CYP2E1, and mediating reactive oxygen species scavenging and accumulation of hypoxia-inducible factor (HIF)-1伪.