EFFECT OF SCHISANDRIN-B ON HEPATIC GLUTATHIONE ANTIOXIDANT SYSTEM IN MICE - PROTECTION AGAINST CARBON-TETRACHLORIDE TOXICITY
EFFECT OF SCHISANDRIN-B ON HEPATIC GLUTATHIONE ANTIOXIDANT SYSTEM IN MICE - PROTECTION AGAINST CARBON-TETRACHLORIDE TOXICITY
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DOI：
10.1055/s-2006-958123
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发表时间：
1995-10-01
期刊：
影响因子：
2.7
通讯作者：
KO, KM
中科院分区：
文献类型：
--
作者：
IP, SP;POON, MKT;KO, KM
用五味子素B （schisandrin B, Sch B）预处理Balb/c雌性小鼠，每日增加剂量（1-4 mmol/kg），连续3天，肝脏谷胱甘肽s转移酶（GST）和谷胱甘肽还原酶（GRD）活性呈剂量依赖性升高。葡萄糖-6-磷酸脱氢酶（G6PDH）、硒-谷胱甘肽过氧化物酶（GPX）和γ -谷氨酰半胱氨酸合成酶（GCS）活性均不同程度下调，且呈剂量依赖性。肝还原性谷胱甘肽（GSH）水平呈双相变化，肝组织匀浆对体外过氧化氢诱导的GSH耗竭具有敏感性，但肝丙二醛含量呈逐渐下降趋势。在CCl4刺激后，Sch B对肝脏GSH抗氧化系统的有益作用更为明显。相同的Sch B预处理方案对四氯化碳（CCl4）诱导的肝毒性具有剂量依赖性保护作用。肝保护与肝脏GSH状态的显著增强相关，正如组织GSH水平的显著增加和组织匀浆对GSH耗尽的相应敏感性降低所表明的那样。GST和GRD活性与非ccl4对照值相比呈线性增加，随着施施Sch b剂量的增加，G6PDH活性也逐渐升高，而GPX活性则适度下调。综上所述，Sch B预处理对肝脏的保护作用可能主要是通过刺激GSH相关酶的活性，增强了肝脏GSH抗氧化系统的功能。
Pretreating female Balb/c mice with schisandrin B (Sch B) at increasing daily doses (1-4 mmol/kg) for 3 days caused dose-dependent increases in hepatic glutathione S-transferase (GST) and glutathione reductase (GRD) activities. However, the activities of glucose-6-phosphate dehydrogenase (G6PDH), Se-glutathione peroxidase (GPX), and gamma-glutamylcysteine synthetase (GCS) were down-regulated to varying degrees in a dose-dependent manner. While there were biphasic changes in hepatic reduced glutathione (GSH) level as well as susceptibility of hepatic tissue homogenates to in vitro peroxide-induced GSH depletion, a gradual decrease in hepatic malondialdehyde content was observed. The beneficial effect of Sch B on the hepatic GSH antioxidant system became more evident after CCl4 challenge. The same Sch B pretreatment regimen caused a dose-dependent protection against carbon tetrachloride (CCl4)-induced hepatotoxicity. The hepatoprotection was associated with significant enhancement in hepatic GSH status, as indicated by the substantial increase in tissue GSH levels and the corresponding decrease in susceptibility of tissue homogenates to GSH depletion. Where the activities of GST and GRD were increased linearly over non-CCl4 control values, there was also a gradual elevation in G6PDH activity upon administration of increasing doses of Sch B. In contrast, GPX activity was moderately down-regulated. The ensemble of results suggests that the hepatoprotection afforded by Sch B pretreatment may mainly be attributed to the enhancement in the functioning of the hepatic GSH antioxidant system, possibly through stimulating the activities of GSH related enzymes.