prostaglandin-d2 and Cholestasis--Intrahepatic

Intrahepatic cholestasis is mainly caused by dysfunction of bile secretion and has limited effective treatment. Rosiglitazone is a synthetic agonist of PPARγ, whose endogenous agonist is 15-deoxy-Δ. Wild-type, hepatocyte-specific PPARγ or Nogo-B knockout mice received intragastric administration of α-naphthylisothiocyanate (ANIT) and/or rosiglitazone, followed by determination of intrahepatic cholestasis and the involved mechanisms. Serum samples from primary biliary cholangitis (PBC) patients and non-PBC controls were analysed for cholestasis-related parameters.. Rosiglitazone prevented wild type, but not hepatocyte-specific PPARγ deficient mice from developing ANIT-induced intrahepatic cholestasis by increasing expression of bile homeostatic proteins, reducing hepatic necrosis, and correcting abnormal serum parameters and enterohepatic circulation of bile. Nogo-B knockout provided protection similar to that of rosiglitazone treatment. ANIT-induced intrahepatic cholestasis decreased 15d-PGJ. Levels of 15d-PGJ

Topics: 1-Naphthylisothiocyanate; Animals; Cholestasis, Intrahepatic; Humans; Mice; PPAR gamma; Prostaglandin D2; Rosiglitazone