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. 1993 Mar;34(3):329–337. doi: 10.1136/gut.34.3.329

Role of eicosanoids, nitric oxide, and afferent neurons in antacid induced protection in the rat stomach.

N Lambrecht 1, M Trautmann 1, R Korolkiewicz 1, M Liszkay 1, B M Peskar 1
PMCID: PMC1374136  PMID: 8472979

Abstract

The mechanism underlying the mucosal protective effect of antacids is still unclear. This study shows that in rats the aluminum containing antacid, hydrotalcit, induces dose dependent protection against gastric mucosal damage caused by ethanol or indomethacin which is considerably enhanced by acidification. Hydrotalcit did not increase gastric mucosal formation or the intraluminal release of prostaglandins, and did not prevent the increase in mucosal leukotriene C4 formation in response to ethanol. Pretreatment with indomethacin did not attenuate the protective effect of unmodified or acidified hydrotalcit. Furthermore, hydrotalcit significantly reduced the gastric damage caused by indomethacin even when it was administered up to 2 hours after the ulcerogen. In indomethacin treated rats, simultaneous administration of hydrotalcit did not affect the concentrations of indomethacin in serum or inflammatory exudates nor did it attenuate the inhibition of prostaglandin release into the exudates. In hydrotalcit treated rats there was no attenuation of the increase in sulphidopeptide leukotriene release or decrease in leukocyte influx into inflammatory exudates elicited by indomethacin administration. Functional ablation of afferent neurons and inhibition of endogenous nitric oxide partially antagonised the protective effect of unmodified, but not of acidified, hydrotalcit. It is concluded that (i) the protective effect of unmodified and acidified hydrotalcit is independent of the eicosanoid system; (ii) protection against indomethacin induced gastric lesions does not require treatment before dosing of the ulcerogen and does not interfere with absorption and anti-inflammatory actions of indomethacin; (iii) endogenous nitric oxide and afferent neurons contribute partly to the effect of unmodified, but not of acidified, hydrotalcit suggesting that different mechanisms mediate their mucosal protective activity.

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Selected References

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  1. Berstad K., Vergin H., Postius S., Weberg R., Szelenyi I., Berstad A. Gastric prostaglandin E2 release induced by aluminium hydroxide and aluminium hydroxide-containing antacids in rats. Effect of low doses and citric acid. Scand J Gastroenterol. 1987 Sep;22(7):884–888. doi: 10.3109/00365528708991930. [DOI] [PubMed] [Google Scholar]
  2. Dembinska-Kiec A., Pallapies D., Simmet T., Peskar B. M., Peskar B. A. Effect of carbenoxolone on the biological activity of nitric oxide: relation to gastroprotection. Br J Pharmacol. 1991 Dec;104(4):811–816. doi: 10.1111/j.1476-5381.1991.tb12511.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. DiJoseph J. F., Borella L. E., Mir G. N. Activated aluminum complex derived from solubilized antacids exhibits enhanced cytoprotective activity in the rat. Gastroenterology. 1989 Mar;96(3):730–735. [PubMed] [Google Scholar]
  4. DiJoseph J. F., Borella L. E., Wells C. L., Mir G. N. Mucosal protective activity of activated aluminum complex. Digestion. 1990;45(1):19–25. doi: 10.1159/000200220. [DOI] [PubMed] [Google Scholar]
  5. Domschke W., Hagel J., Ruppin H., Kaduk B. Antacids and gastric mucosal protection. Scand J Gastroenterol Suppl. 1986;125:144–150. doi: 10.3109/00365528609093830. [DOI] [PubMed] [Google Scholar]
  6. Fitzpatrick L. R. Protection by acidified Maalox against indomethacin-induced gastric antral ulceration in hamsters. Digestion. 1991;50(1):1–6. doi: 10.1159/000200733. [DOI] [PubMed] [Google Scholar]
  7. Galeazzi R. L. The effect of an antacid on the bioavailability of indomethacin. Eur J Clin Pharmacol. 1977 Aug 17;12(1):65–68. doi: 10.1007/BF00561407. [DOI] [PubMed] [Google Scholar]
  8. Gamse R. Capsaicin and nociception in the rat and mouse. Possible role of substance P. Naunyn Schmiedebergs Arch Pharmacol. 1982 Sep;320(3):205–216. doi: 10.1007/BF00510129. [DOI] [PubMed] [Google Scholar]
  9. Gugler R., Allgayer H. Effects of antacids on the clinical pharmacokinetics of drugs. An update. Clin Pharmacokinet. 1990 Mar;18(3):210–219. doi: 10.2165/00003088-199018030-00003. [DOI] [PubMed] [Google Scholar]
  10. Hagel J., Renner H., Hirsch M., Weig G., Kaduk B., Ruppin H., Domschke W. Gastric cytoprotection by antacids and papaverine in rats. Hepatogastroenterology. 1982 Dec;29(6):271–274. [PubMed] [Google Scholar]
  11. Holzer P., Lippe I. T. Stimulation of afferent nerve endings by intragastric capsaicin protects against ethanol-induced damage of gastric mucosa. Neuroscience. 1988 Dec;27(3):981–987. doi: 10.1016/0306-4522(88)90201-1. [DOI] [PubMed] [Google Scholar]
  12. Holzer P., Pabst M. A., Lippe I. T., Peskar B. M., Peskar B. A., Livingston E. H., Guth P. H. Afferent nerve-mediated protection against deep mucosal damage in the rat stomach. Gastroenterology. 1990 Apr;98(4):838–848. doi: 10.1016/0016-5085(90)90005-l. [DOI] [PubMed] [Google Scholar]
  13. Hurwitz A. Antacid therapy and drug kinetics. Clin Pharmacokinet. 1977 Jul-Aug;2(4):269–280. doi: 10.2165/00003088-197702040-00003. [DOI] [PubMed] [Google Scholar]
  14. Konturek S. J., Brzozowski T., Drozdowicz D., Nauert C. Role of intragastric pH in cytoprotection by antacids in rats. Eur J Pharmacol. 1990 Feb 6;176(2):187–195. doi: 10.1016/0014-2999(90)90527-d. [DOI] [PubMed] [Google Scholar]
  15. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  16. Peskar B. M., Respondek M., Müller K. M., Peskar B. A. A role for nitric oxide in capsaicin-induced gastroprotection. Eur J Pharmacol. 1991 May 30;198(1):113–114. doi: 10.1016/0014-2999(91)90572-8. [DOI] [PubMed] [Google Scholar]
  17. Peskar B. M. Role of leukotriene C4 in mucosal damage caused by necrotizing agents and indomethacin in the rat stomach. Gastroenterology. 1991 Mar;100(3):619–626. doi: 10.1016/0016-5085(91)80005-t. [DOI] [PubMed] [Google Scholar]
  18. Peskar B. M., Trautmann M., Nowak P., Peskar B. A. Release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid and cysteinyl-leukotrienes in carrageenin-induced inflammation: effect of non-steroidal anti-inflammatory drugs. Agents Actions. 1991 Jul;33(3-4):240–246. doi: 10.1007/BF01986569. [DOI] [PubMed] [Google Scholar]
  19. Preclik G., Stange E. F., Gerber K., Fetzer G., Horn H., Ditschuneit H. Alimentary tract and pancreas. Stimulation of mucosal prostaglandin synthesis in human stomach and duodenum by antacid treatment. Gut. 1989 Feb;30(2):148–151. doi: 10.1136/gut.30.2.148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Prieto R., Martinez-Tobed A., Fábregas J. L., Beneyto J. E. In vitro comparison of the antacid potencies of almagate in tablets and suspension with those of other commercially available antacid preparations. Arzneimittelforschung. 1984;34(10A):1360–1364. [PubMed] [Google Scholar]
  21. Szelenyi I., Lanz R. Release of cytoprotective PGE2 from cultured macrophages induced by antacids and sucralfate. Agents Actions. 1986 Jun;18(3-4):375–380. doi: 10.1007/BF01965000. [DOI] [PubMed] [Google Scholar]
  22. Szelenyi I., Postius S., Engler H. Evidence for a functional cytoprotective effect produced by antacids in the rat stomach. Eur J Pharmacol. 1983 Apr 8;88(4):403–406. doi: 10.1016/0014-2999(83)90594-0. [DOI] [PubMed] [Google Scholar]
  23. Szelényi I. Functional cytoprotection by certain antacids. Acta Physiol Hung. 1984;64(3-4):259–268. [PubMed] [Google Scholar]
  24. Tarnawski A., Hollander D., Gergely H., Stachura J. Comparison of antacid, sucralfate, cimetidine, and ranitidine in protection of the gastric mucosa against ethanol injury. Am J Med. 1985 Aug 30;79(2C):19–23. doi: 10.1016/0002-9343(85)90567-4. [DOI] [PubMed] [Google Scholar]
  25. Vergin H., Kori-Lindner C. Putative mechanisms of cytoprotective effect of certain antacids and sucralfate. Dig Dis Sci. 1990 Nov;35(11):1320–1327. doi: 10.1007/BF01536735. [DOI] [PubMed] [Google Scholar]
  26. Weberg R., Berstad K., Berstad A. Acute effects of antacids on gastric juice components in duodenal ulcer patients. Eur J Clin Invest. 1990 Oct;20(5):511–515. doi: 10.1111/j.1365-2362.1990.tb01894.x. [DOI] [PubMed] [Google Scholar]
  27. Whittle B. J., Lopez-Belmonte J., Moncada S. Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat. Br J Pharmacol. 1990 Mar;99(3):607–611. doi: 10.1111/j.1476-5381.1990.tb12977.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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