Ursodeoxycholic acid reduces protein levels and nucleation-promoting activity in human gallbladder bile

doi:10.1053/gast.1996.v110.pm8613013

Gastroenterology

Volume 110, Issue 4, April 1996, Pages 1225-1237

https://doi.org/10.1053/gast.1996.v110.pm8613013 Get rights and content

Abstract

BACKGROUND & AIMS: Ursodeoxycholic acid prevents gallstone formation in selected patients. The aim of this study was to examine whether decreased concentration and nucleation-promoting activity of various proteins contribute to this beneficial effect. METHODS: Gallbladder bile of 13 patients with cholesterol gallstones treated with ursodeoxycholic acid (10 mg/kg(-1)/day(-1)) and of 13 untreated patients were compared. RESULTS: Total protein concentration in gallbladder bile (2.8 +/- 0.6 vs. 6.7 +/- 1.3 mg/mL; P=0.008) and concanavalin A-binding fraction (0.16 +/- 0.03 vs. 0.42 +/- 0.07 mg/mL; P=0.003) were strongly decreased by ursodeoxycholic acid therapy. Significant decreases were also found for gallbladder bile alpha1-acid glycoprotein, haptoglobin, immunoglobulin (Ig) A, IgG, gamma-glutamyl transpeptidase, and aminopeptidase N but not for IgM, mucin, or beta- glucuronidase. Decreases were most pronounced for proteins of canalicular membrane origin. Gallbladder bile total protein correlated with cholesterol saturation index (r=0.54; P=0.0047) but not with bile salt hydrophobicity index. Crystallization-promoting activity of the concanavalin A-binding fraction (assessed by nephelometry and microscopic examination) was also significantly decreased by ursodeoxycholic acid. CONCLUSIONS: Ursodeoxycholic acid strongly decreases levels of various proteins and nucleation-promoting activity in bile. (Gastroenterology 1996 Apr;110(4):1225-37)

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Also, decreasing biliary mucin content with aspirin decreases risk of gallstones in the prairie dog model29 and risk of gallstone recurrence after nonsurgical treatment in humans.30 Ursodeoxycholic acid also decreases biliary mucin contents.31 Meal ingestion induces considerable gallbladder emptying (up to 70%–80% of fasting gallbladder volumes) by releasing the hormone cholecystokinin from the upper intestine.
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Background/Aims: Although cholesterol gallstone patients exhibit higher biliary cholesterol saturation than pigment stone patients, underlying mechanisms that affect stone type are unknown. We hypothesized that pronucleating proteins, hydrophobic bile salts or apolipoprotein E genotype affect stone type. We therefore compared these putative factors in cholesterol and pigment stone patients.
Methods: In 74 cholesterol and 12 pigment stone patients, bile lipids, various pronucleating proteins, crystallization and apolipoprotein E genotype were determined.
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2003, Digestive and Liver Disease
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2002, Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
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