Acanthoic acid, a diterpene in Acanthopanax koreanum, protects acetaminophen-induced hepatic toxicity in mice

The protective effect of a diterpenoid acanthoic acid (M) isolated from Acanthopanax koreanum Nakai was investigated in acetaminophen (APAP)-induced hepatic toxicity. Drug-induced hepatotoxicity induced by an intraperitoneal (i p.) injection of 300 mg/kg (sub-lethal dose) of APAP. Pretreatment with AA (50 and 100 mg/kg) orally 2 h before the APAP administration attenuated the APAP-Induced acute increase in serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activites, replenished the depleted hepatic glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (CSH-Px) activities, decreased malondialdehyde (MDA) level and considerably reduced the histopathological alterations in a manner similar to silymarin (Sily) Immunohistochemical analyses also demonstrated that AA could reduce the appearance of necrosis regions as well as caspase-3 and hypoxia inducible factor-1 alpha (HIF-1 alpha) expression in liver tissue Our results indicated that AA protected liver tissue from the oxidative stress elicites by APAP-inducecl liver damage and suggestes that the hepatic protection mechanism of AA would relate to antioxidation and hypoxia factor on APAP-induced hepatotoxicity (C) 2009 Elsevier GmbH All rights reserved.