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

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 alpha 1l-acid glycoprotein, heptoglobin, immunoglobulin (lg) 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.