STRUCTURE-ACTIVITY RELATIONSHIP OF SCHISANDRINS IN ENHANCING LIVER MITOCHONDRIAL GLUTATHIONE STATUS IN CCL4-POISONED MICE

ATM: To explore whether the methylenedioxy group and cyclooctadiene ri ng of the dibenzocyclooctadiene skeleton of schisandrins (Sch) play a role in the liver mitochondrial glutathione system status enhancing ac tivity. METHOD: The effects of three dibenzoclooctadiene derivatives, Sch A, Sch B, Sch C, and a synthetic intermediate of Sch C, (dimethyl biphenyl dicarboxylate, DBD) on carbon tetrachloride (CCl4)-hepatotoxi city and liver mitochondrial glutathione status were examined in mice. RESULTS: Pretreating mice with intragastric Sch B, Sch C, or DBD 1. m mol.kg(-1).d(-1) for 3 d protected against CCl4-hepatotoxicity. The he patoprotection afforded by Sch B or Sch C pretreatment was associated with increases in liver mitochondrial reduced glutathione (mtGSH) leve l and glutathione reductase (mtGRD) activity, an indication of enhance d mitochondrial glutathione status. In contrast, the hepatoprotective action of DBD was not accompanied by any detectable changes in mtGSH l evel and mtGRD activity. CONCLUSION: Both the methylenedioxy group and the cyclooctadiene ring of the dibenzocyclooctadiene molecule are imp ortant structural determinants in the enhancement of Liver mitochondri al glutathione status.