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 x 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 (CCl4) challenge. Pretreatment with Sch B could sustain the hepatic mitochondrial GSH level in CCl4-intoxicated mice and protect against CCl4 hepatotoxicity. BHT pretreatment did not produce any protective effect on CCl4-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 CCl4-intoxicated mice. Moreover, Sch B pretreatment prevented the CCl4-induced decrease in the hepatic alpha-tocopherol (VE) level. However, Sch B inhibited NADPH oxidation in mouse liver microsomes incubated with CCl4 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 CCl4 hepatotoxicity. The possible inhibition of CCl4 metabolism by Sch B may also contribute to its hepatoprotective action.
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Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong.
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D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D034242:Cyclooctanes; D005260:Female; D017705:Lignans; D008099:Liver / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009249:NADP / Q000378:metabolism; D011083:Polycyclic Compounds / Q000494:pharmacology*
D000975:Antioxidants; D034242:Cyclooctanes; D017705:Lignans; D011083:Polycyclic Compounds; C015499:schizandrin B; D002084:Butylated Hydroxytoluene; D009249:NADP; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase