EFFECT OF SCHISANDRIN-B ON HEPATIC GLUTATHIONE ANTIOXIDANT SYSTEM IN MICE - PROTECTION AGAINST CARBON-TETRACHLORIDE TOXICITY

Pretreating female Balb/c mice with schisandrin B (Sch B) at increasin g daily doses (1-4 mmol/kg) for 3 days caused dose-dependent increases in hepatic glutathione S-transferase (GST) and glutathione reductase (GRD) activities. However, the activities of glucose-6-phosphate dehyd rogenase (G6PDH), Se-glutathione peroxidase (GPX), and gamma-glutamylc ysteine synthetase (GCS) were down-regulated to varying degrees in a d ose-dependent manner. While there were biphasic changes in hepatic red uced glutathione (GSH) level as well as susceptibility of hepatic tiss ue homogenates to in vitro peroxide-induced GSH depletion, a gradual d ecrease in hepatic malondialdehyde content was observed. The beneficia l effect of Sch B on the hepatic GSH antioxidant system became more ev ident after CCl4 challenge. The same Sch B pretreatment regimen caused a dose-dependent protection against carbon tetrachloride (CCl4)-induc ed hepatotoxicity. The hepatoprotection was associated with significan t enhancement in hepatic GSH status, as indicated by the substantial i ncrease in tissue GSH levels and the corresponding decrease in suscept ibility of tissue homogenates to GSH depletion. Where the activities o f GST and GRD were increased linearly over non-CCl4 control values, th ere was also a gradual elevation in G6PDH activity upon administration of increasing doses of Sch B. In contrast, GPX activity was moderatel y down-regulated. The ensemble of results suggests that the hepatoprot ection afforded by Sch B pretreatment may mainly be attributed to the enhancement in the functioning of the hepatic GSH antioxidant system, possibly through stimulating the activities of GSH related enzymes.