Summary
Bismuth salts are currently used as monotherapy or in combination with antibiotics for the treatment ofHelicobacter pylori-associated peptic ulcer disease. Besides encouraging clinical results with colloidal bismuth subcitrate (CBS), there is an ongoing fear of organ toxicity with the use of bismuth salts. To study potential toxic effects of CBS under short-term exposure, we tested the influence of CBS on amylase secretion from isolated rat pancreatic acinar cells under basal conditions and following carbachol (CCh) and ceruletide (CRT) stimulation. Basal secretion was reduced by 8.9±9.6% (n=10) (mean±SEM) (P<0.05), 5.2±9.2% (P<0.05), 9.4±6.4% (P<0.01), and 6.2±12.2% (P<0.05) with 0.001, 0.01, 0.1, and 1 μg/ml CBS, respectively. With 10 μg/ml and 100 μg/ml CBS, basal amylase secretion was increased in a dose-dependent manner, by 13.7±11.7% (P<0.05) and 24.5±12.8% (P<0.01). CCh (10−5 M)-and CRT (3×10−10 M)-stimulated secretory responses were not altered significantly by any of the CBS doses used. In concentrations above 1 μg/ml, CBS increased pancreatic amylase secretion. Amylase secretion in response to secretagogues was not affected by CBS. These findings are unlikely to be associated with a toxic effect of CBS on exocrine pancreatic acinar cell function.
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References
Amsterdam A, Jamieson JD (1972) Structural and functional characterization of isolated pancreatic exocrine cells. Proc Natl Acad Sci USA 69:3028–3032
Bader JP (1987) The safety profile of De-Nol. Digestion 37[Suppl 2]:53–59
Bianchi Porro G, Lazzroni M, Petrillo M, De Nicola C (1984) Relapse rates in duodenal ulcer patients formerly treated with bismuth subcitrate or maintained with cimetidine. Lancet II:698
Chandler DE, Williams JA (1974) Pancreatic acinar cells: effects of lanthanum ions on amylase release and calcium ion fluxes. J Physiol (London) 243:831–846
Coghill SB, Hopwood D, McPherson S, Hislop S (1983) The ultrastructural localization of De-Nol (colloidal tripotassium dicitrato bismuthate TDB) in the upper gastrointestinal tract of man and rodents following oral and instrumental administration. J Pathol 139:105–114
Gavey CJ, Szeto ML, Nwokolo CU, Sercombe J, Pounder RE (1989) Bismuth accumulates in the body during treatment with tripotassium dicitrato bismuthate. Aliment Pharmacol Ther 3:21–28
Hamilton I, O'Connor HJ, Wood NC, Bradbury I, Axon ATR (1986) Healing and recurrence of duodenal ulcer after treatment with tripotassium dicitrato bismuthate tablets or cimetidine. Gut 27:106–110
Hillemand P, Palliere M, Laquais B, Bouvet P (1977) Traitement bismuthique et bismuthemie. Sem Hop Paris 53:1663–1669
Kang JY, Piper DW (1982) Cimetidine and colloidal bismuth in treatment of chronic duodenal ulcer. Comparison of initial healing and recurrence after healing. Digestion 23:73–79
Lane MR, Lee SR (1988) Recurrence of duodenal ulcer after medical treatment. Lancet I:1147–1149
Langer GA, Frank JS (1972) Lanthanum in heart cell culture: effect on calcium exchange correlated with its localization. J Cell Biol 54:441–445
Lee FI, Samloff IM, Hardman M (1985) Comparison of tripotassium dicitratobismuthate tablets with ranitidine in healing and relapse of duodenal ulcers. Lancet I:1299–1302
Lee SP, Lim TH, Pybus J, Clarke AC (1970) The tissue distribution of orally administered bismuth in the rat. Clin Exp Pharmacol Physiol 7:319–324
Lock M, Nichol H, Ketola-Pirie C (1987) Binding of bismuth to cell components: clue to mode of action and side effects. Can Med Assoc J 137:991–992
Marks IN (1988) Site-protective agents. Balliere's Clin Gastroenterol 2:609–620
Martin DF, Hollanders D, May SJ, Ravenscroft MM, Tweedle DE, Miller JP (1981) Difference in relapse rates of duodenal ulcer after healing with cimetidine or tripotassium dicitrato bismuthate. Lancet I:7–10
Nwokolo CU, Gavey CJ, Smith JTL, Pounder RE (1989) The absorption of bismuth from oral doses of tripotassium dicitrato bismuthate. Aliment Pharmacol Ther 3:29–39
Shreeve DR, Klass HJ, Jones PE (1983) Comparison of cimetidine and tripotassium dicitrato-bismuthate in healing and relapse of duodenal ulcers. Digestion 28:96–101
Streb H, Schulz I (1983) Regulation of cytosolic free Ca2+ concentration in acinar cells of rat pancreas. Am J Physiol 245:G347-G357
Tytgat GNJ (1987) Colloidal bismuth subcitrate in peptic ulcer—a review. Digestion 37: [Suppl 2]:31–41
Van Breeman C, Weer P de (1970) Lanthanum inhibition of45Ca efflux from the squid giant axon. Nature 226:760–761
Vantrappen G, Schuurmans P, Rutgeerts P, Janssens J (1982) A comparative study of colloidal bismuth subcitrate and cimetidine on the healing and recurrence of duodenal ulcer. Scand J Gastroenterol 80:23–30
Wakasugi H, Stolze H, Haase W, Schulz I (1981) Effect of La3+ on secretagogue-induced Ca2+ fluxes in rat isolated pancreatic acinar cells. Am J Physiol 240:G281–289
Weiss GB, Goodman FR (1969) Effects of lanthanum on contraction, calcium distribution and45Ca movements in intestinal smooth muscle. J Pharmacol Exp Ther 169:46–55
Winship KA (1983) Toxicity of bismuth salts. Adverse Drug React Acute Poisoning Rev 2:103–121
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Kemmer, T.P., Malfertheiner, P., Bode, G. et al. Influence of colloidal bismuth subcitrate on enzyme secretion from isolated rat pancreatic acinar cells. Res. Exp. Med. 192, 415–422 (1992). https://doi.org/10.1007/BF02576299
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DOI: https://doi.org/10.1007/BF02576299