Stimulation of bile flow and inhibition of biliary secretion of taurocholate and leukotriene C4 in thioacetamide-induced liver fibrosis.
In order to study the relation of hepatic fibrogenesis to biliary elimination, female Uje:WIST rats were treated with thioacetamide (TAA). This treatment results in single cell necrosis, fibrosis, nodular parenchyma und proliferation of bile ducts. In isolated perfused livers from pretreated rats, liver hemodynamics, bile flow, and secretion of taurocholate and leukotriene C4 were determined. After TAA-pretreatment, sinusoidal efflux of glucose and pyruvate was reduced increasing lactate/pyruvate ratio threefold. Biliary secretion of [14C]taurocholate and [3H]leukotriene C4 was lowered by 47% and 35%, respectively, compared to controls. In contrast, basal bile flow was increased after TAA-treatment. The beta-adrenergic agonist isoproterenol stimulated bile flow threefold over controls. The increased stimulation was correlated with increased liver weight after TAA-treatment. We postulate that both increased bile flow and stimulation by isoproterenol are due to proliferation of bile ducts and increased ductular bile secretion partially compensating for disturbed hepatocellular secretion.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001652:Bile Ducts / Q000187:drug effects / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D017997:Leukotriene C4 / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000378:metabolism*; D013853:Thioacetamide
D001786:Blood Glucose; D013853:Thioacetamide; D017997:Leukotriene C4; D013656:Taurocholic Acid; D007545:Isoproterenol