earticle

영어

Acetaminophen (APAP; paracetamol) is widely used as an antipyretic and analgesic, and that in high doses can result in extensive liver injury. The protective effects of an aqueous extract from the fruits of a Stauntonia hexaphylla (S. hexaphylla) on acetaminophen (APAP)-induced hepatotoxicities and the possible protective mechanisms involved were investigated in mice. Pretreatment with an aqueous extracts from fruits of S. hexaphylla (AEFSH) prior to the administration of APAP significantly prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activity and hepatic lipid peroxidation in a dose-dependent manner. APAP-induced hepatotoxicity was also essentially prevented as evidenced by liver histopathology. Hepatic glutathione levels and glutathione-S-transferase activities were not affected by treatment with AEFSH alone, but pretreatment with CK protected the APAP-induced depletion of hepatic glutathione levels. The effects of CK on cytochrome P450 (P450) 2E1, the major isozyme involved in APAP bioactivation, were investigated. In microsomal incubations, AEFSH effectively inhibited the P450 2E1-dependent p-nitrophenol and aniline hydroxylase. These results indicate that the protective effects of S. hexaphylla against the APAP-induced hepatotoxicity may, at least in part, be due to its ability to block P450-mediated APAP bioactivation.