Effects of lipopolysaccharide on the biliary excretion of bile acids and organic anions in rats.
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.
Hojo
Makoto
M
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Sano
Naoyo
N
Takikawa
Hajime
H
D000818:Animals; D000838:Anions; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013654:Taurine / Q000737:chemistry
D000838:Anions; D001647:Bile Acids and Salts; D008070:Lipopolysaccharides; D013654:Taurine