Compensatory induction of liver efflux transporters in response to ANIT-induced liver injury is impaired in FXR-null mice.

ABSTRACT: Alpha-naphthyl isothiocyanate (ANIT) is a hepatotoxicant that produces acute intrahepatic cholestasis in rodents. Farnesoid X receptor (FXR) and pregnane X receptor (PXR) are two major bile acid sensors in liver. The purpose of this study was to characterize the regulation of hepatic transporters by FXR and PXR during ANIT-induced liver injury. Wild-type, FXR-null, and PXR-null mice were administered ANIT (75 mg/kg, po) and evaluated 48 h later for hepatotoxicity and messenger RNA (mRNA) expression of basolateral uptake (sodium taurocholate-cotransporting polypeptide, organic anion transporting polypeptide [Oatp] 1a1, Oatp1a4, Oatp1b2) and efflux transporters (organic solute transporter [Ost] alpha, Ostbeta, multidrug resistance-associated protein [Mrp] 3, Mrp4), as well as canalicular tra

SUBMITTER: Cui YJ 

PROVIDER: S-EPMC2696329 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature