The crucial antioxidant action of schisandrin B in protecting against carbon tetrachloride hepatotoxicity in mice: A comparative study with butylated hydroxytoluene

A comparison between the effects of schisandrin B (Sch B) and butylated hydroxytoluene (BHT) treatments on hepatic antioxidant status was made to identify the critical antioxidant action of Sch B involved in hepatoprotection in mice. Whereas Sch B treatment (3 mmol/kg/day × 3, p.o.) increased the hepatic mitochondrial-reduced glutathione (GSH) level, BHT treatment at the same dosage regimen decreased it. However, both 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 became more apparent after carbon tetrachloride (CCl 4) challenge. Pretreatment with Sch B could sustain the hepatic mitochondrial GSH level in CCl 4-intoxicated mice and protect against CCl 4 hepatotoxicity. BHT pretreatment did not produce any protective effect on CCl 4-induced GSH depletion in mitochondrion and hepatocellular damage. Although both Sch B and BHT treatments increased hepatic ascorbic acid (VC) level in control animals, only Sch B pretreatment sustained a high hepatic VC level in CCl 4-intoxicated mice. Moreover, Sch B pretreatment prevented the CCl 4-induced decrease in the hepatic α-tocopherol (VE) level. However, Sch B inhibited NADPH oxidation in mouse liver microsomes incubated with CCl 4 in vitro, whereas BHT stimulated this oxidation. The ensemble of results suggests that the ability to sustain the hepatic mitochondrial GSH level and the hepatic VC and VE levels may represent the crucial antioxidant action of Sch B in protection against CCl 4 hepatotoxicity. The possible inhibition of CCl 4 metabolism by Sch B may also contribute to its hepatoprotective action.