against Carbon Tetrachloride Liver Toxicity by Enantiomers of Schisandrin B
Associated with Differential Changes in Hepatic Glutathione Antioxidant System
Ko K-M.; Poon M.K.T.; Ip S-P.; Wu K.
Two enantiomers of schisandrin B (Sch B), an active ingredient isolated from the fruit of Schisandra chinensis , were chirally separated. Pretreating mice with (+)Sch B or (-)Sch B at a daily oral dose of 1 mmol/kg for 3 days protected against carbon tetrachloride (CCl 4 ) hepatotoxicity, as evidenced by highly significant decreases in plasma alanine aminotransferases activity and hepatic malondialdehyde level. The hepatoprotection afforded by pretreatment with the enantiomers was associated with increases in hepatic glutathione S-transferases and glutathione reductase (GRD) activities as well as mitochondrial reduced glutathione (GSH) level. However, only the (+)Sch B pretreated animals showed a reduction in the extent of CCl 4 -induced inhibition of hepatic Se-glutathione peroxidase activity. In addition, (+)Sch B pretreatment produced a more potent stimulatory effect on hepatic GRD activity and mitochondrial GSH level in CCl 4 -treated mice. The differential ability between (+)Sch B and (-)Sch B in enhancing hepatic glutathione antioxidant system in CCl 4 -intoxicated mice may implicate the presence of a chiral-/stereo-specific intracellular target for mediating the antioxidant action of Sch B.