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 increasing 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 dehydrogenase (G6PDH), Se-glutathione peroxidase (GPX), and gamma-glutamylcysteine synthetase (GCS) were down-regulated to varying degrees in a dose-dependent manner. While there were biphasic changes in hepatic reduced glutathione (GSH) level as well as susceptibility of hepatic tissue homogenates to in vitro peroxide-induced GSH depletion, a gradual decrease in hepatic malondialdehyde content was observed. The beneficial effect of Sch B on the hepatic GSH anti-oxidant system became more evident after CCl4 challenge. The same Sch B pretreatment regimen caused a dose-dependent protection against carbon tetrachloride (CCl4)-induced hepatotoxicity. The hepatoprotection was associated with significant enhancement in hepatic GSH status, as indicated by the substantial increase in tissue GSH levels and the corresponding decrease in susceptibility of tissue homogenates to GSH depletion. Where the activities of GST and GRD were increased linearly over non-CCl4 control values, there was also a gradual elevation in G6PDH activity upon administration of increasing doses of Sch B. In contrast, GPX activity was moderately down-regulated. The ensemble of results suggests that the hepatoprotection afforded by Sch B pretreatment may mainly be attributed to the enhancement in the functioning of the hepatic GSH anti-oxidant system, possibly through stimulating the activities of GSH related enzymes.
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology / Q000378:metabolism*; D034242:Cyclooctanes; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D017705:Lignans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D010946:Plants, Medicinal / Q000737:chemistry; D011083:Polycyclic Compounds / Q000494:pharmacology*
D000975:Antioxidants; D034242:Cyclooctanes; D017705:Lignans; D011083:Polycyclic Compounds; C015499:schizandrin B; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione