Ursodeoxycholic acid reduces protein levels and nucleation-promoting activity in human gallbladder bile.
OBJECTIVE
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.
Van Erpecum
K J
KJ
Department of Gastroenterology, University Hospital Utrecht, The Netherlands.
Portincasa
P
P
Eckhardt
E
E
Go
P M
PM
VanBerge-Henegouwen
G P
GP
Groen
A K
AK
D000328:Adult; D000704:Analysis of Variance; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D002769:Cholelithiasis / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003208:Concanavalin A / Q000378:metabolism; D003460:Crystallization; D005260:Female; D005704:Gallbladder / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008297:Male; D008859:Microscopy, Polarization; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D009077:Mucins; D010713:Phosphatidylcholines; D011506:Proteins; D003208:Concanavalin A; D014580:Ursodeoxycholic Acid; D002784:Cholesterol