Asiatic acid derivatives protect primary cultures of rat hepatocytes against carbon tetrachloride-induced injury via the cellular antioxidant system.
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.
Lee
Mi Kyeong
MK
College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, 599 Gwanak-Ro, Gwanak-Gu, Seoul 151-742, Republic of Korea.
Kim
Seung Hyun
SH
Yang
Hyekyung
H
Lim
Doo-Yeon
DY
Ryu
Je-Ho
JH
Lee
Eung Seok
ES
Jew
Sang-Sup
SS
Park
Hyeung-Guen
HG
Sung
Sang Hyun
SH
Kim
Young Choong
YC
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
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