Abstract: AIM: To study the cytoprotective action and mechanisms of isoliquiritigenin(ISL)on acute injury of hepatocytes induced by acetaminophen. METHODS: Rat hepatocytes in sandwich cultures were randomly divided into control group, model group, ISL group and ISL plus L-NAME groups.The acute injury of hepatocytes was induced by being exposed into acetaminophen (20 mmol L)for 12 h.In the pretreatment groups, L-NAME and or ISL were given before administration of acetaminophen.The activities of ALT and AST in medium were measured by using enzyme assays.The CYP2E1 expression in hepatocytes was determined by using enzyme assays and semiquantitative RT-PCR.The contents of cGMP and cAMP in hepatocytes were measured by radioimmunoassay.The activites of nuclear transcription regulation factors such as NF-κB were determined by sandwich ELISA. RESULTS: ISL (5-20 μmol L)reduced the increase of the ALT and AST levels dose-dependently. And the cytochrome P450(CYP)2E1(aniline hydroxylase, ANH)activity was decreased by 75.7% maximumly and the mRNA expression was inhibited in a dose (50-200 μg mL)dependent manner, the maximum inhibitory rate was 78.7%.In addition, ISL remarkably increased the glutathione content decreased by acetaminophen of hepatocytes. L-NAME (2 mmol L)could reverse the protective effect of ISL (20 μmol L).ISL could not reverse the decrease of the level of cAMP induced by acetaminophen of hepatocytes but ISL could dose-dependently enhance the intracellular cGMP content (to 4.75 times maximumly)and suppress the NF-κB activation, the inhibitory rates were 24.8%,37.3% and 64.1%. CONCLUSION: ISL can protect the injury of hepatocytes induced by acetaminophen.It may be relate to the inhibition of NF-κB activation and down regulation of CYP2E1 expression via NO-cGMP pathways.

Key words: isoliquiritigenin, acetaminophen, hepatocyte, CYP2E1, cGMP