title: Asiatic acid derivatives protect primary cultures of rat hepatocytes against carbon tetrachloride-induced injury via the cellular antioxidant system.
abstract: We attempted to elucidate the hepatoprotective mechanism of two asiatic acid (AS) derivatives, 3beta,23-dihydroxyurs-2-oxo-12-ene-28-oic acid (AS-10) and 3beta,23-dihydroxyurs-12-ene-28-oic acid (AS-14), which exhibited significant protective activity against carbon tetrachloride (CCl4)-induced hepatotoxicity in primary cultures of rat hepatocytes. Our findings showed that AS-10 and AS-14 preserved the level of glutathione and the activities of antioxidant enzymes such as glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. In addition, these compounds ameliorated lipid peroxidation, as demonstrated by a reduction in the production of malondialdehyde. Furthermore, AS-10 and AS-14 did not restore the reduced total GSH level by BSO, indicating that the hepatoprotective activities of these compounds may be involved, in part, by regulating GSH synthesis. From these results, we suggest that both AS-10 and AS-14 exerted their hepatoprotective activities against CCl4-induced injury by preserving the cellular antioxidative defense system.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, 599 Gwanak-Ro, Gwanak-Gu, Seoul 151-742, Republic of Korea.
authors.forename: Mi Kyeong
authors.initials: MK
authors.lastname: Lee
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Hyekyung
authors.initials: H
authors.lastname: Yang
authors.forename: Doo-Yeon
authors.initials: DY
authors.lastname: Lim
authors.forename: Je-Ho
authors.initials: JH
authors.lastname: Ryu
authors.forename: Eung Seok
authors.initials: ES
authors.lastname: Lee
authors.forename: Sang-Sup
authors.initials: SS
authors.lastname: Jew
authors.forename: Hyeung-Guen
authors.initials: HG
authors.lastname: Park
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Sung
authors.forename: Young Choong
authors.initials: YC
authors.lastname: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes
chemical_list: C543278:3,23-dihydroxyurs-12-ene-28-oic acid; C543277:3,23-dihydroxyurs-2-oxo-12-ene-28-oic acid; D000975:Antioxidants; D012503:Saponins; D014315:Triterpenes; D002251:Carbon Tetrachloride