Protective effects and mechanism of bicyclol against sepsis-induced fulminant hepatitis in mice
AIM:To investigate the preventive ef-fect and potential mechanism of bicyclol on sepsis-induced fulminant hepatitis(FH).METHODS:The FH model was established by lipopolysaccharide(LPS)/D-galactose(D-Gal),and mice were orally ad-ministrated with bicyclol and the survival rate with-in 24 h was recorded.The activities of glutamate aminotransferase(AST),alanine aminotransferase(ALT),catalase(CAT)and superoxide dismutase(SOD),and the content of glutathione(GSH)and malondialdehyde(MDA)in liver tissue were mea-sured by chemiluminescence.The histopathological changes of liver were examined by HE and TUNEL staining.The levels of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)and interleukin 6(IL-6)were measured using ELISA.The protein expression of nuclear transcription factor kappa B inhibitory protein α(IκBα),phosphorylated IκBα(p-IκBα),nu-clear transcription factor kappa B(NF-κB),nuclear red blood cell 2 related factor 2(Nrf2),NAD(P)H:quinone oxidoreductase 1(NQO1),and heme oxy-genase 1(HO1)in liver tissue was examined by Western blotting.RESULTS:Pre-treatment with bi-cyclol improved survival ratio of FH mice,reduced ALT and AST activities,alleviated liver tissue le-sions,and lowered Suzuki score.Meanwhile,the levels of TNF-α,IL-1β,IL-6 and MDA were reduced,the GSH level and CAT and SOD enzyme activities were increased,the protein expression of p-IκBαand nuclear NF-κB was down-regulated,and the protein levels of IκBα,nuclear Nrf2,NQO1 and HO1 were up-regulated.Moreover,post-treatment with Bicyclol also significantly reduced ALT and AST activities in FH mice.CONCLUSION:Bicyclol exhibit-ed remarkable hepaprotective efects on FH caused by LPS/D-Gal,the potential mechanism underlying the anti-infammatory and antioxidative activities of Bicyclol might be associated with the suppression of NF-κB signaling pathway and the activation of Nrf2/NQO1/HO1 signaling pathway.
万方数据
维普
