METHYLENEDIOXY GROUP AS DETERMINANT OF SCHISANDRIN IN ENHANCING HEPATIC MITOCHONDRIAL GLUTATHIONE IN CARBON TETRACHLORIDE-INTOXICATED MICE

As a preliminary approach to exploring whether the methylenedioxy grou p of the dibenzocyclooctadiene skeleton of schisandrins plays an impor tant role in hepatic mitochondrial-reduced glutathione (GSH) stimulato ry activity, we examined the effects of three schisandrins, namely sch isandrin A (Sch A), schisandrin B (Sch B), and schisandrin C (Sch C), on carbon tetrachloride (CCl4) hepatotoxicity and hepatic mitochondria l GSH status in mice. Pretreating mice with Sch A at a daily oral dose of 1 mmol/kg for 3 days did not protect against CCl4 hepatotoxicity, whereas pretreatment with Sch B or Sch C at the same dosage regimen pr oduced almost complete protection. The hepatoprotection afforded by Sc h B or Sch C pretreatment was associated with significant increases in the hepatic mitochondrial GSH level and glutathione reductase (EC 1.6 .4.2) activity. Our results indicate that the methylenedioxy group of the dibenzocyclooctadiene skeleton of schisandrin is an important stru ctural determinant in the stimulation of hepatic mitochondrial GSH, pa rticularly under conditions of CCl4 intoxication. (C) 1997 Elsevier Sc ience Inc.