Intrahepatic cholestasis is a kind of clinical syndrome along with hepatotoxicity which caused by intrahepatic and systemic accumulations of
bile acid. There are several crucial generating factors of the pathogenesis of
cholestasis, such as
inflammation, dysregulation of
bile acid transporters and oxidative stress.
SIRT1 is regarded as a class III
histone deacetylase (HDAC). According to a set of researches,
SIRT1 is one of the most important factors which can regulate the hepatic
bile acid metabolism.
SRT1720 is a kind of activator of
SIRT1 which is 1000 times more potent than
resveratrol, and this paper is aimed to study its protective influence on hepatotoxicity and
cholestasis induced by
alpha-naphthylisothiocyanate (ANIT) in mice. The findings revealed that
SRT1720 treatment increased FXR and Nrf2 gene expressions to shield against hepatotoxicity and
cholestasis induced by ANIT. The
mRNA levels of hepatic
bile acid transporters were also altered by
SRT1720. Furthermore,
SRT1720 enhanced the antioxidative system by increasing Nrf2, SOD, GCLc, GCLm, Nqo1, and HO-1 gene expressions. In conclusion, a protective influence could be provided by
SRT1720 to cure ANIT-induced hepatotoxicity and
cholestasis, which was partly through FXR and Nrf2 activations. These results indicated that
SIRT1 could be regarded as a therapeutic target to cure the
cholestasis.