五味子对扑热息痛肝脏毒性的保护作用

五味子果仁乙醇提取物(五仁醇)及其有效成分之一五味子醇乙(醇乙),预先24h给药能显著降低大剂量扑热息痛(400mg/kg)肝中毒所致的小鼠死亡率,并防止肝内谷胱甘肽(GSH)的耗竭,增强肝微粒体代谢扑热息痛的速度,血中扑热息痛含量下降。从这些结果推测,五仁醇和醇乙的抗扑热息痛肝脏毒性作用可能是通过对肝微粒体细胞色素P-450的诱导作用,调整肝微粒体对扑热息痛代谢的途径,减少毒性代谢产物的生成量。醇乙是五味子对抗扑热息痛肝脏毒性的主要有效成分。

PROTECTION BY FRUCTUS SCHIZANDRAE AGAINST ACETAMINOPHEN HEPATOTOXICITY IN MICE

Our previous studies found that the alcoholic extract of the kernels of Fructus Schizandrae (AKS) and its certain components significantly protected against CCl_4 hepatotoxicity in mice. This paper reports the protective action of AKS and schisandrol B (one of the components) against acetaminophen hepatotoxicity in mice.Mice were treated with AKS 0.5g/kg (calculated as raw materials 5g/kg) and schisandrol B 200 mg/kg, separately, 24 hours before ip injection of acetaminophen 400 mg/kg. The number of mice died and depletion of liver glutathione induced by acetaminophen were reduced significantly. Blood acetaminophen concentration of schisandrol B-treated mice was much lower than that of the control mice, whereas the rate of acetaminophen metabolism by liver microsomes from schisandrol B-treated mice was higher than that from control mice. AKS and schisandrol B were shown to be phenobarbital-like inducer of microsomal cytochrome p-450. However, phenobarbital (100 mg/kg) pretreatment was not shown to revent the death of mice and acetaminophen(400 mg/kg ip.) induced depletion of liver glutathione.It appears that the hepato-protective action of AKS and schisandrol B against acetaminophen might be due to induction of a new form of cytochrome p-450 which modified the pathway of acetaminophen metabolism, thereby, decreased the formation of toxic intermediate (s).