Hepatic aquaporin-8 (AQP8) water channels and oxidative stress are early affected during extrahepatic cholestasis in bile duct ligated (BDL) rats

Background: Interruption of bile flow during extrahepatic cholestasis may result in liver failure. Here we investigate for the first time if both AQP8-mediated osmotic water movement and oxidative stress might be early affected in an animal model of cholestasis. Materials and methods: Wistar rats underwent proximal BDL or sham operation; at days 1, 3, and 7 we measured liver histology, AQP8 (expression, subcellular localization), oxidative stress as total, oxidized glutathione (GSH, GSSG), and protein sulphydril (PSH, cytosolic/mitochondrial fractions). Results: BDL livers showed progressive intrahepatic bile duct dilatation, bile aggregates, inflammatory changes, cell degeneration, mitochondrial swelling. At day 3, intracellular but not plasma membrane AQP8 was decreased by 75% (P< 0.001). At day 7, AQP8 was decreased both intracellularly (-67%) and in plasma membranes (-56%) (P< 0.05), suggesting defective translocation or membrane insertion of AQP8. Cytosolic GSH and PSH gradually decreased while GSSG increased (P