Ursodeoxycholic acid reduces lipid peroxidation and mucin secretagogue activity in gallbladder bile of patients with cholesterol gallstones.
BACKGROUND
Recently it has been postulated that gallbladder mucin hypersecretion observed in the pathogenesis of cholesterol gallstone disease may be induced by biliary lipid peroxidation. Ursodeoxycholic acid treatment reduces mucin concentration and the formation of cholesterol crystals in the gallbladder bile of patients with cholesterol gallstones and this effect might be mediated by a decrease of biliary lipid peroxidation.


METHODS
In a double-blind, placebo-controlled trial patients with symptomatic cholesterol gallstones received either ursodeoxycholic acid (750 mg daily) (n = 10) or placebo (n = 12) 10-12 days prior to cholecystectomy. As a marker for lipid peroxidation malondialdehyde was measured in bile together with mucin concentration. In addition, the mucin secretagogue activity of the individual bile samples was assessed in cultured dog gallbladder epithelial cells.


RESULTS
Ursodeoxycholic acid therapy resulted in a significant reduction of lipid peroxidation in bile as determined by the biliary malondialdehyde concentration (1.36 +/- 0.28 vs. 2.05 +/- 0.38 micromol L(-1); P < 0.005) and the malondialdehyde (micromol L(-1))/total bile acid (mmol L(-1)) ratio (0.02 +/- 0.005 vs. 0.06 +/- 0.01; P < 0.001). Furthermore, a decrease in mucin concentrations (0.7 +/- 0.3 vs. 1.3 +/- 0.5 mg mL(-1); P < 0.005) and of the mucin secretagogue activity of gallbladder bile (0.9 +/- 0.2 vs. 2.2 +/- 0.3 times control; P < 0.001) was observed.


CONCLUSIONS
The reduction of lipid peroxidation and mucin secretagogue activity of gallbladder bile induced by ursodeoxycholic acid treatment may contribute to the beneficial effects of this drug on gallbladder bile composition and symptoms in cholesterol gallstone patients.
Division of Clinical Pharmacology and Toxicology, University Hospital, Zurich, Switzerland.
C
C
Jüngst
N
N
Sreejayan
B
B
Zündt
I
I
Müller
F W
FW
Spelsberg
T P
TP
Hüttl
G A
GA
Kullak-Ublick
R
R
del Pozo
D
D
Jüngst
C
C
von Ritter
D000328:Adult; D000368:Aged; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D002756:Cholagogues and Choleretics / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005704:Gallbladder / Q000378:metabolism*; D042882:Gallstones / Q000188:drug therapy*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000187:drug effects* / Q000378:metabolism; D010919:Placebos; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D009077:Mucins; D010919:Placebos; D014580:Ursodeoxycholic Acid