Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease

✍ Scribed by Ritter, C. ;Niemeyer, A. ;Lange, V. ;M�hrle, W. ;Richter, W.O. ;Meyer, L. ;Brandl, H. ;Pozo, R. ;J�ngst, D.

• Publisher: Springer-Verlag
• Year: 1993
• Tongue: English
• Weight: 450 KB
• Volume: 71
• Category: Article
• ISSN: 1432-1440
• DOI: 10.1007/bf00185606

✦ Synopsis

Maximilians-Univer sit,it Mfinchen

Summary. There is experimental evidence that inhibition of cyclooxygenase with nonsteroidal anti-inflammatory drugs may decrease cholesterol gallstone formation and mitigate biliary pain in gallstone patients. The mechanisms by which NSAIDs exert these effect are unclear. In a prospective, controlled clinical trial we examined the effects of oral indomethacin on the composition of human gallbladder bile. The study included 28 patients with symptomatic cholesterol or mixed gallstones. Of these, 8 were treated with 3 x 25 mg indomethacin daily for 7 days prior to elective cholecystectomy while 20 received no treatment and served as controls. Bile and tissue samples from the gallbladder were obtained during cholecystectomy. Indomethacin tissue levels in the gallbladder mucosa, as assessed by HPLC, were 1.05_+0.4 ng/mg wet weight, a concentration known to inhibit effectively cyclooxygenase activity. Nevertheless, no differences between the treated and untreated groups were found in the concentrations of biliary mucus glycoprotein (0.94___ 0.27 versus 0.93 ___ 0.32 mg/ml) or total protein (5.8 +0.9 versus 6.4+ 1.3 mg/ml), cholesterol saturation (1.3 _+ 0.2 versus 1.5 +_ 0.2), or nucleation time (2.0 +_ 3.0 versus 1.5 + 2.0 days). However, biliary viscosity, measured using a lowshear rotation viscosimeter, was significantly lower in patients receiving indomethacin treatment (2.9+0.6 versus 5.6_+ 1.2 mPa.s; P<0.02). In conclusion, in man oral indomethacin decreases bile viscosity without alteration of bile lithogenicity or biliary mucus glycoprotein content. Since mucus glycoproteins are major determinants of bile viscosity, an alteration in mucin macromolecular composition may conceivably cause the indomethacin-induced decrease in biliary viscosity and explain the beneficial effects of nonsteroidal anti-inflammatory drugs in gallstone disease.