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- W3136387998 abstract "Abstract Cholestasis is one of the most severe manifestations of liver injury and has limited therapeutic options. Allopurinol (AP), an inhibitor of uric acid (UA) synthesis, was reported to prevent liver damage in several liver diseases. However, whether AP protects against intrahepatic cholestatic liver injury and what is the role of UA in the pathogenesis of cholestasis remain unknown. In this study, we reported that AP attenuated liver injury in a mouse model of intrahepatic cholestasis induced by alpha-naphthylisothiocyanate (ANIT). AP showed no significant effect on glutathione depletion, inflammation, or bile acid metabolism in livers of ANIT-treated mice. Instead, AP significantly improved fatty acid β-oxidation in livers of ANIT-treated mice, which was associated with activation of PPARα. The protective effect of AP on cholestatic liver injury was not attributable to the depletion of UA, because both exogenous and endogenous UA prevented liver injury in ANIT-treated mice via inhibition of NF-kB-mediated inflammation. In conclusion, the present study provides a new perspective for the therapeutic use of AP and the role of UA in cholestatic liver injury." @default.
- W3136387998 created "2021-03-29" @default.
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- W3136387998 date "2021-03-22" @default.
- W3136387998 modified "2023-10-14" @default.
- W3136387998 title "Allopurinol Protects Against Cholestatic Liver Injury in Mice Not Through Depletion of Uric Acid" @default.
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- W3136387998 doi "https://doi.org/10.1093/toxsci/kfab034" @default.
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