THESIS
1998
xviii, 180 leaves : ill. ; 30 cm
Abstract
Previous studies have demonstrated the hepatoprotective effect of Schisandrin B (Sch B) against carbon tetrachloride (CCl
4) toxicity. Recently, many studies have attributed the protective effect of Sch B to its free radical scavenging activity. Preliminary studies in our laboratory showed that the scavenging activity was not sufficient to explain the hepatoprotection produced by Sch B treatment. Therefore, a detailed investigation is necessary in order to define the protective mechanisms of Sch B treatment.
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Previous studies have demonstrated the hepatoprotective effect of Schisandrin B (Sch B) against carbon tetrachloride (CCl
4) toxicity. Recently, many studies have attributed the protective effect of Sch B to its free radical scavenging activity. Preliminary studies in our laboratory showed that the scavenging activity was not sufficient to explain the hepatoprotection produced by Sch B treatment. Therefore, a detailed investigation is necessary in order to define the protective mechanisms of Sch B treatment.
Using CCl
4-induced toxicity as a model of free radical-mediated hepatocellular damage, our results showed that the hepatoprotection produced by Sch B pretreatment may be due to (1) an increase in reduced glutathione (GSH) levels in hepatic tissue and mitochondria; (2) an increase in hepatic ascorbate concentration; (3) an enhancement in glutathione-S-transferase activity and (4) inhibition of CCl
4 metabolism. A comparative study of Sch B with butylated hydroxytoluene, a synthetic phenolic antioxidant, suggested that the increase in hepatic GSH might be a crucial factor in producing the protection. Studies on the hepatoprotective effect of various Schisandrins suggested that both enhancement of hepatic glutathione status and inhibition of CCl
4 metabolism were involved in the protective action of Sch B treatment. However, the enhancement of hepatic glutathione status was more important for hepatoprotection. Treating mice with 1,3-bis(2-chloroethyl)- 1 -nitrosourea (BCNU), a specific inhibitor of glutathione reductase, decreased hepatic glutathione reductase activity as well as GSH concentration. However, BCNU treatment could not completely abrogate the hepatoprotective action of Sch B in CCl
4-treated mice. A compensatory increase in hepatic ascorbate concentration by BCNU treatment in Sch B-pretreated mice suggested that the hepatoprotective effect of Sch B treatment may be attributed to the enhancement in the functioning of an integrated antioxidant system. This concept was supported by the protection produced by Sch B pretreatment against hepatocellular damage induced by different chemical toxicants.
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