HEPATOCYTE TRANSPORT OF BILE-ACIDS AND ORGANIC-ANIONS IN ENDOTOXEMIC RATS - IMPAIRED UPTAKE AND SECRETION

Background & Aims: In sepsis, Intrahepatic cholestasis occurs frequent ly, suggesting impaired hepatocyte transport of bile acids and organic anions. The aim of the study was to define the magnitude, time course , and the site of impaired biliary secretion in a rat sepsis model, Me thods: Maximal transport for two bite acids (cholyltaurine and chenode oxycholyltaurine) and two organic anions (sulfobromophthalein and sulf olithocholyltaurine) was measured in isolated perfused fivers at Vario us times after lipopolysaccharide injection, Basolateral and canalicul ar liver plasma membrane vesicles were used to characterize the impair ment in hepatocyte transport. Results: Maximal hepatocyte transport wa s reduced for all compounds by 60%-81% compared with controls, Bile ac id-independent bile flow was reduced by 51%. Impairment was maximal 12 hours after endotoxin injection and recovered thereafter, in basolate ral plasma membrane vesicles, sodium-dependent transport for bile acid s was reduced by 36%-47%, Sodium-independent transport of organic anio ns was reduced by 40%-55%, Adenosine triphosphate-stimulated transport was greatly decreased in canalicular vesicles prepared from endotoxem ic animals for all four compounds probably because of a reduced number of transport molecules, based on kinetic studies. Conclusions: Basola teral and canalicular bile acid and organic anion transport are marked ly impaired in endotoxemia. These mechanisms may contribute to the cho lestasis of sepsis.