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. 1996 Jun;38(6):826–831. doi: 10.1136/gut.38.6.826

Sulphydryl blocker induced gastric damage is ameliorated by scavenging of free radicals.

F Karmeli 1, E Okon 1, D Rachmilewitz 1
PMCID: PMC1383187  PMID: 8984018

Abstract

BACKGROUND: Sulphydryl compounds and nitric oxide are essential in maintaining gastric mucosal integrity. AIMS: To characterise the gastric damage induced by a sulphydryl blocker, to evaluate the role of nitric oxide in its pathogenesis, and to reveal its possible prevention by scavenging of free radicals. METHODS: Gastritis was induced in rats by addition of iodoacetamide (0.1%) to the drinking water, with and without daily intragastric administration of TEMPOL. After death, the stomach was resected, washed, lesion area assessed, and mucosal inflammatory mediators, myeloperoxidase and nitric oxide synthase activities were determined. RESULTS: Administration of iodoacetamide induced gastric mucosal erosions present for up to two weeks. Myeloperoxidase activity was increased for up to seven days and nitric oxide synthase activity was significantly decreased for up to 14 days. Treatment for seven days with the free radical scavenger, TEMPOL, decreased by 68% the damage induced by iodoacetamide. CONCLUSIONS: Gastric damage induced by iodoacetamide, a sulphydryl alkylator, accompanied by inhibition of nitric oxide synthase activity shows the important contribution of sulphydryl compounds and nitric oxide to the maintenance of gastric mucosal integrity. Nitric oxide donation and scavenging of free radicals may be a novel approach to prevent gastric damage.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bradley P. P., Priebat D. A., Christensen R. D., Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982 Mar;78(3):206–209. doi: 10.1111/1523-1747.ep12506462. [DOI] [PubMed] [Google Scholar]
  2. Bush P. A., Gonzalez N. E., Griscavage J. M., Ignarro L. J. Nitric oxide synthase from cerebellum catalyzes the formation of equimolar quantities of nitric oxide and citrulline from L-arginine. Biochem Biophys Res Commun. 1992 Jun 30;185(3):960–966. doi: 10.1016/0006-291x(92)91720-b. [DOI] [PubMed] [Google Scholar]
  3. Gardiner S. M., Compton A. M., Bennett T., Palmer R. M., Moncada S. Control of regional blood flow by endothelium-derived nitric oxide. Hypertension. 1990 May;15(5):486–492. doi: 10.1161/01.hyp.15.5.486. [DOI] [PubMed] [Google Scholar]
  4. Hauser J., Szabo S. Extremely long protection by pyrazole derivatives against chemically induced gastric mucosal injury. J Pharmacol Exp Ther. 1991 Feb;256(2):592–598. [PubMed] [Google Scholar]
  5. Li T., Zhang X. J. [Role of sulfhydryl compounds in the oxygen radical induced injury of isolated gastric mucosal cells]. Sheng Li Xue Bao. 1992 Aug;44(4):386–393. [PubMed] [Google Scholar]
  6. Masuda E., Kawano S., Nagano K., Tsuji S., Takei Y., Tsujii M., Oshita M., Michida T., Kobayashi I., Nakama A. Endogenous nitric oxide modulates ethanol-induced gastric mucosal injury in rats. Gastroenterology. 1995 Jan;108(1):58–64. doi: 10.1016/0016-5085(95)90008-x. [DOI] [PubMed] [Google Scholar]
  7. Meister A., Anderson M. E. Glutathione. Annu Rev Biochem. 1983;52:711–760. doi: 10.1146/annurev.bi.52.070183.003431. [DOI] [PubMed] [Google Scholar]
  8. Pihan G., Regillo C., Szabo S. Free radicals and lipid peroxidation in ethanol- or aspirin-induced gastric mucosal injury. Dig Dis Sci. 1987 Dec;32(12):1395–1401. doi: 10.1007/BF01296666. [DOI] [PubMed] [Google Scholar]
  9. Rachmilewitz D., Karmeli F., Okon E., Bursztyn M. Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity. Gut. 1995 Aug;37(2):247–255. doi: 10.1136/gut.37.2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Rachmilewitz D., Karmeli F., Okon E., Samuni A. A novel antiulcerogenic stable radical prevents gastric mucosal lesions in rats. Gut. 1994 Sep;35(9):1181–1188. doi: 10.1136/gut.35.9.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rachmilewitz D., Karmeli F., Okon E. Sulfhydryl blocker-induced rat colonic inflammation is ameliorated by inhibition of nitric oxide synthase. Gastroenterology. 1995 Jul;109(1):98–106. doi: 10.1016/0016-5085(95)90273-2. [DOI] [PubMed] [Google Scholar]
  12. Salter M., Knowles R. G., Moncada S. Widespread tissue distribution, species distribution and changes in activity of Ca(2+)-dependent and Ca(2+)-independent nitric oxide synthases. FEBS Lett. 1991 Oct 7;291(1):145–149. doi: 10.1016/0014-5793(91)81123-p. [DOI] [PubMed] [Google Scholar]
  13. Sharon P., Ligumsky M., Rachmilewitz D., Zor U. Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine. Gastroenterology. 1978 Oct;75(4):638–640. [PubMed] [Google Scholar]
  14. Vaananen P. M., Meddings J. B., Wallace J. L. Role of oxygen-derived free radicals in indomethacin-induced gastric injury. Am J Physiol. 1991 Sep;261(3 Pt 1):G470–G475. doi: 10.1152/ajpgi.1991.261.3.G470. [DOI] [PubMed] [Google Scholar]
  15. Yamada Y., Marshall S., Specian R. D., Grisham M. B. A comparative analysis of two models of colitis in rats. Gastroenterology. 1992 May;102(5):1524–1534. doi: 10.1016/0016-5085(92)91710-l. [DOI] [PubMed] [Google Scholar]

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