THE CRUCIAL ANTIOXIDANT ACTION OF SCHISANDRIN-B IN PROTECTING AGAINSTCARBON-TETRACHLORIDE HEPATOTOXICITY IN MICE - A COMPARATIVE-STUDY WITH BUTYLATED HYDROXYTOLUENE

A comparison between the effects of schisandrin B (Sch B) and butylate d hydroxytoluene (BHT) treatments on hepatic antioxidant status was ma de to identify the critical antioxidant action of Sch B involved in he patoprotection in mice. Whereas Sch B treatment (3 mmol/kg/day x 3, p. o.) increased the hepatic mitochondrial-reduced glutathione (GSH) leve l, BHT treatment at the same dosage regimen decreased it. However, bot h Sch B and BHT increased, albeit to a different extent, the activity of mitochondrial glutathione reductase. The differential effect of Sch B and BHT treatment on hepatic mitochondrial glutathione status becam e more apparent after carbon tetrachloride (CCl4) challenge. Pretreatm ent with Sch B could sustain the hepatic mitochondrial GSH level in CC l4-intoxicated mice and protect against CCl4 hepatotoxicity. BHT pretr eatment did not produce any protective effect on CCl4-induced GSH depl etion in mitochondrion and hepatocellular damage. Although both Sch B and BHT treatments increased hepatic ascorbic acid (VC) level in contr ol animals, only Sch B pretreatment sustained a high hepatic VC level in CCl4-intoxicated mice. Moreover, Sch B pretreatment prevented the C Cl4-induced decrease in the hepatic alpha-tocopherol (VE) level. Howev er, Sch B inhibited NADPH oxidation in mouse liver microsomes incubate d with CCl4 in vitro, whereas BHT stimulated this oxidation. The ensem ble of results suggests that the ability to sustain the hepatic mitoch ondrial GSH level and the hepatic VC and VE levels may represent the c rucial antioxidant action of Sch B in protection against CCl4 hepatoto xicity. The possible inhibition of CCl4 metabolism by Sch B may also c ontribute to its hepatoprotective action. Copyright (C) 1996 Elsevier Science Inc.