HEPATOCYTE TIGHT-JUNCTIONAL PERMEABILITY IS INCREASED IN RAT EXPERIMENTAL COLITIS

Background & Aims: Hepatobiliary complications occur in inflammatory b owel disease and may be caused by the translocation of intestinal toxi ns from portal blood into bile through leaky hepatocyte tight junction s. The role of tight junctions in the pathogenesis of hepatobiliary co mplications in experimental inflammatory bowel disease was investigate d. Methods: Colitis was induced in rats by intracolonic instillation o f trinitrobenzene sulfonic acid, The function of hepatocellular tight junctions was evaluated in perfused livers by measuring early (paracel lular) horseradish peroxidase excretion into the bile and by electron microscopy and semiquantitative analysis of lanthanum penetration thro ugh the tight junction and into bile canaliculi. Immunofluorescent loc alization of cingulin and ZO-1 was used to study the structure of hepa tocyte junctions, Results: Colitis was associated with increased serum bilirubin and bile acid concentrations, a 2.5-fold increase in parace llular biliary excretion of horseradish peroxidase, and a ninefold inc rease in lanthanum permeability, Liver histology and cingulin and ZO-1 localizations were similar to normal liver, Conclusions: Experimental colitis is associated with hepatobiliary complications and an increas ed hepatocyte tight junctional permeability to horseradish peroxidase and lanthanum. Subtle alterations in tight junction function may be in volved ire the pathogenesis of hepatobiliary injuries in inflammatory bower disease.