Oestradiol 17 beta-glucuronide increases tight-junctional permeability in rat liver

By using rat liver perfusion under one-pass conditions with a single pulse of horseradish peroxidase (HRP), the biliary output of HRP was used as an indicator of paracellular permeability change caused by the cholestatic compound oestradiol 17 beta-glucuronide (E17G). Since E17G reduced bile flow, we have also used, during the assessment of junctional permeability after E17G treatment, the choleretic compound taurodehydrocholate to enhance bile flow back to control levels. At both low and restored bile flow rates, the acute administration of E17G (3.4 mumol) increased the HRP peak height, thereby indicating that one of the hepatotoxic actions of E17G is to increase the permeability of hepatic tight junctions. The action of E17G in affecting bile acid secretion and biliary volume are also explored.