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 CCl₄ 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).