Effects of lipopolysaccharide on the biliary excretion of bile acids and organic anions in rats
Autor: | Hajime Takikawa, Makoto Hojo, Naoyo Sano |
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Rok vydání: | 2003 |
Předmět: |
Anions
Lipopolysaccharides Male medicine.medical_specialty Lipopolysaccharide Taurine Statistics Nonparametric Bile Acids and Salts Rats Sprague-Dawley Temocapril Sepsis chemistry.chemical_compound Cholestasis Western blot In vivo Internal medicine medicine Animals Bile Hepatology medicine.diagnostic_test Leukotriene C4 business.industry Gastroenterology medicine.disease Bile Salt Export Pump Rats Endocrinology chemistry business medicine.drug |
Zdroj: | Journal of Gastroenterology and Hepatology. 18:815-821 |
ISSN: | 1440-1746 0815-9319 |
Popis: | Background: Lipopolysaccharide is known to be a cause of cholestasis associated with sepsis. It has also recently been reported to down-regulate the basolateral and canalicular transporters. The aim of the present study was to examine simultaneously the effect of lipopolysaccharide on the biliary excretion of typical substrates of bile salt export pump and multidrug resistance protein 2 in vivo, and the effect of lipopolysaccharide on the amount of these transporters. Methods: After intravenous administration of O127:B8-derived lipopolysaccharide (2.5 mg/kg), the biliary excretion of taurocholate and various organic anions was studied, and the protein levels of bile salt export pump and multidrug resistance protein 2 in the crude liver membrane was determined by western blot analysis. Results: Lipopolysaccharide decreased the biliary excretion of tracer amounts of taurocholate, leukotriene C4, taurolithocholate-3-sulfate and temocapril without affecting bile flow. The biliary excretion of high doses of taurocholate and sulfobromophthalein was markedly inhibited by lipopolysaccharide. Lipopolysaccharide decreased bile salt export pump levels in the liver plasma membrane fraction to 48% of control rats, and markedly decreased multidrug resistance protein 2 levels to 17% of control rats. Conclusions: These findings support the hypothesis that down-regulation of the canalicular transporters by lipopolysaccharide causes the impairment of the biliary excretion of bile acids and organic anions in cholestasis of sepsis prior to the decrease of bile flow. © 2003 Blackwell Publishing Asia Pty Ltd |
Databáze: | OpenAIRE |
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