Summary
There is experimental evidence that inhibition of cyclooxygenase with nonsteroidal anti-inflammatory drugs may decrease cholesterol gall-stone formation and mitigate biliary pain in gall-stone 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 gall-bladder bile. The study included 28 patients with symptomatic cholesterol or mixed gallstones. Of these, 8 were treated with 3 × 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 low-shear 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.
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Abbreviations
- NSAIDs:
-
nonsteriodal anti-inflammatory drugs
References
Abell LL, Levy BB, Brodie BB, Kendall FE (1952) A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem 195:357–366
Broomfield PH, Chopra R, Sheinbaum RC, Bonorris GG, Silverman A, Schoenfield LJ, Marks JW (1988) Effects of ursodeoxycholic acid and aspirin on the formation of lithogenic bile and gallstones during loss of weight. New Engl J Med 319:1567–1572
Carey MC (1978) Critical table for calculation of the cholesterol saturation of native bile. J Lipid Res 19:945–955
Fiske CH, Subbarow Y (1925) The colorimetric determination of phosphorus. J Biol Chem 66:375–400
Flower RJ, Vane JR (1974) Inhibition of prostaglandin biosynthesis. Biochem Pharmacol 23:1439–1450
Holan KR (1979) Nucleation time: a key factor in the pathogenesis of cholesterol gallstone disease. Gastroenterology 77:611–617
Hood K, Gleeson D, Ruppin DC, Dowling RH (1988) Prevention of gallstone recurrence by non-steroidal anti-inflammatory drugs. Lancet II:1223–1225
Jüngst D, Lang T, von Ritter C, Paumgartner G (1991) Role of high total protein in gallbladder bile in the formation of cholesterol gallstones. Gastroenterology 100:1724–1729
Kent PW, Allen A (1968) The biosynthesis of intestinal mucins: the effect of salicylate on glycoprotein biosynthesis by sheep colonic and human gastric mucosal tissues in vitro. Biochem J 106:645–658
Lee SP, Carey MC, LaMont JT (1981) Aspirin prevention of cholesterol gallstone formation in prairie dogs. Science 211:1429–1431
Lee SP, LaMont JT, Carey MC (1981) Role of gallbladder mucus hypersecretion in the evolution of cholesterol gallstones: Studies in prairie dog. J Clin Invest 67:1712–1723
Lukie BE, Forstner GG (1972) Synthesis of intestinal clycoproteins: inhibition of (I-C14)glucosamine incorporation by sodium salicylate in vitro. Biochim Biophys Acta 273:380–388
Mantle M, Allen A (1978) A colorimetric assay for glycoproteins based on the periodic acid/Schiff stain. Biochem Soc Trans 6:607–609
O'Donnell LJD, Wilson P, Guest P, Catnach SM, McLean A, Wickham JEA, Fairclough PD (1992) Indomethacin and postprandial gallbladder emptying. Lancet 339:269–271
O'Leary DP, LaMorte WW, Scott TE, Booker ML, Stevenson J (1991) Inhibition of prostaglandin synthesis fails to prevent gallbladder mucin hypersecretion in the cholesterolfed prairie dog. Gastroenterology 101:812–820
Rhodes M, Allen A, Dowling RH, Murphy G, Lennard TWJ (1992) Inhibition of human gall bladder mucus synthesis in patients undergoing cholecystectomy. Gut 33:1113–1117
Rhodes M, Allen A, Lennard TWJ (1992) Mucus glycoprotein biosynthesis in the human gall bladder: inhibition by aspirin. Gut 33:1109–1112
Shankar V, Damodaran C, Sekharan PC (1988) Isolation of alkaloids and glycosides from tissue following enzymic digestion. Forensic Sci Int 37:243–248
Smith BF, Peetermans JA, Tanaka T, LaMont JT (1989) Subunit interactions and physical properties of bovine gallbladder mucin. Gastroenterology 97:179–187
Talalay P (1960) Enzymatic analysis of steroid hormones. Biochem Anal 8:119–143
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Dedicated to Prof. Dr. G. Paumgartner on the occasion of his 60th birthday
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von Ritter, C., Niemeyer, A., Lange, V. et al. Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease. Clin Investig 71, 928–932 (1993). https://doi.org/10.1007/BF00185606
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DOI: https://doi.org/10.1007/BF00185606