| Objective : To investigate the protective effects and underlying mechanisms of FA on acetaminophen-induced hepatotoxicity.Methods : Balb/c mice were randomly divided into six groups,including blank control group,FA control group,APAP group and three dasages of FA intervention groups.Fasted mice were given APAP(350mg/kg body weight)intraperitioneally to induced acute liver injury and sacrificed after 18 h of APAP challenging.Different concentrations(10,30,100 mg/kg)of FA were gavaged every 8 h a time for three times before APAP administration.Hepatotoxicity was evaluated by the activities of ALT and AST in serum,HE,TUNEL and Caspase-3 activity in the liver tissues.The expression of CYP 2E1 was analysed through western blot and qRT-PCR.The content of GSH,activities of SOD and CAT were measured with kit.The level of TNF-? and IL-1? in serum were detected by ELISA.The protein expressions of TLR4,p-IRAK1,p-I?B and p-p38 were assayedthrough western blot.Results:1.Ferulic acid reduced the levels of ALT and AST induced by APAP in dose-dependent manner.2.Ferulic acid inhibited pathologic damage and apoptosis in the liver.HE outcome demonstrated large area of necrosis and bleeding induced by APAP were decreased.TUNEL and Caspase-3 activity analysis showed that ferulic acid pretreatment restrained hepatocyte apoptosis caused by APAP.3.Ferulic acid significantly down-regulated the expression of CYP 2E1 showed by mRNA and protein level from APAP challenged liver tissues.4.Ferulic acid obviously suppressed APAP-induced oxidative stress reflected by enhanced activities of SOD and CAT and increased content of GSH.5.Ferulic acid significantly decreased TNF-? and IL-1? level in serum with APAP administration.6.Ferulic acid reduced the protein expressions induced by APAP,which including TLR4,p-IRAK1,p-I?B,p-p38.Conclusion:FA attenuated APAP-induced hepatotoxicity which may be based on down-regulating CYP 2E1 and suppressing TLR4-mediated inflammation. |
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