Ip S P, Ko K M
Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong.
Biochem Pharmacol. 1996 Dec 13;52(11):1687-93. doi: 10.1016/s0006-2952(96)00517-5.
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.
比较了五味子醇甲（Sch B）和丁基羟基甲苯（BHT）处理对肝脏抗氧化状态的影响，以确定Sch B在小鼠肝脏保护中所涉及的关键抗氧化作用。Sch B处理（3 mmol/kg/天×3，口服）可提高肝脏线粒体还原型谷胱甘肽（GSH）水平，而相同剂量方案的BHT处理则使其降低。然而，Sch B和BHT均能不同程度地提高线粒体谷胱甘肽还原酶的活性。在四氯化碳（CCl4）攻击后，Sch B和BHT处理对肝脏线粒体谷胱甘肽状态的差异效应变得更加明显。Sch B预处理可维持CCl4中毒小鼠的肝脏线粒体GSH水平，并防止CCl4肝毒性。BHT预处理对CCl4诱导的线粒体GSH耗竭和肝细胞损伤未产生任何保护作用。虽然Sch B和BHT处理均能提高对照动物的肝脏抗坏血酸（VC）水平，但只有Sch B预处理能维持CCl4中毒小鼠的高肝脏VC水平。此外，Sch B预处理可防止CCl4诱导的肝脏α-生育酚（VE）水平降低。然而，Sch B在体外与CCl4孵育的小鼠肝微粒体中抑制NADPH氧化，而BHT则刺激这种氧化。这些结果表明，维持肝脏线粒体GSH水平以及肝脏VC和VE水平的能力可能代表了Sch B在预防CCl4肝毒性中的关键抗氧化作用。Sch B对CCl4代谢的可能抑制作用也可能有助于其肝脏保护作用。
