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Esophagitis in sprague-dawley rats is mediated by free radicals

  • Esophageal, Gastric, And Duodenal Disorders
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Abstract

Free radical-mediated esophagitis was studied during duodenogastroesophageal reflux (mixed reflux) or acid reflux in rats. The influence of reflux on esophageal glutathione levels was also examined. Mixed reflux caused more gross mucosal injury than acid reflux. Gross mucosal injury occurred in the mid-esophagus. Total glutathione (GSH) in the esophageal mucosa of control rats was highest in the distal esophagus. The time course of esophageal GSH in rats treated by mixed reflux showed a significant decrease 4 hr after initiation of reflux, followed by a significant increase from the 12th hour on. Mucosal GSH was increased in both reflux groups after 24 hr but significantly more so in the mixed than in the acid reflux group. The free radical scavenger superoxide dismutase (SOD) prevented esophagitis and was associated with decreased GSH levels. GSH depletion by buthionine sulfoximine (BSO) prevented esophagitis and stimulated SOD production in the esophageal mucosa. It is concluded that gastroesophageal reflux is associated with oxidative stress in the esophageal mucosa. The lower GSH levels in the mid-esophagus may predispose to damage in this area. Duodenogastroesophageal reflux causes more damage than pure acid reflux. Oxidative stress leads to GSH depletion of the esophageal mucosa in the first few hours following damage but then stimulates GSH production. GSH depletion by BSO does not worsen esophagitis since it increases the esophageal SOD concentration.

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References

  1. DeMeester TR, Wernly JA, Bryant GH, Little AG, Skinner DB: Clinical andin vitro analysis of determinants of gastroesophageal competence: A study of the principles of antireflux surgery. Am J Surg 137:39–46, 1979

    PubMed  Google Scholar 

  2. Zaninotto G, DeMeester TR, Schwizer W, Johansson KE, Cheng SC: The lower esophageal sphincter in health and disease. Am J Surg 155:104–111, 1988

    PubMed  Google Scholar 

  3. Zaninotto G, DiMario F, Costantini M, Baffa R, Germanà B, Dal Santo PL, Rugge M, Bolzan M, Naccarato R, Ancona E: Oesophagitis and pH of refluxate: An experimental and clinical study. Br J Surg 79:161–164, 1992

    PubMed  Google Scholar 

  4. Attwood SEA, DeMeester TR, Bremner CG, Barlow AP, Hinder RA: Alkaline gastroesophageal reflux: Implications in the development of complications in Barrett's columnar-lined lower esophagus. Surgery 106:764–770, 1989

    PubMed  Google Scholar 

  5. Gillen P, Keeling P, Byrne PJ, Healy M, O'Moore RR, Hennessy TP: Implication of duodenogastric reflux in the pathogenesis of Barrett's oesophagus. Br J Surg 75:540–543, 1988

    PubMed  Google Scholar 

  6. Fiorucci S, Santucci L, Chiucchiù S, Morelli A: Gastric acidity and gastroesophageal reflux patterns in patients with esophagitis. Gastroenterology 103:855–861, 1992

    PubMed  Google Scholar 

  7. Stein HJ, Feussner H, DeMeester TR, Siewert JR: Alkaline gastroesophageal reflux: Assessment by ambulatory esophageal aspiration and pH monitoring. Am J Surg 167:163–167, 1994

    PubMed  Google Scholar 

  8. Stein HJ, Barlow AP, DeMeester TR, Hinder RA: Complications of gastroesophageal reflux disease. Role of the lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and duodenogastric reflux. Ann Surg 216:35–43, 1992

    PubMed  Google Scholar 

  9. Saeki S, Redmond EJ. Complications of gastroesophageal reflux disease.In Gastroesophageal Reflux Disease. Medical Intellegence Unit, 1st ed. RA Hinder (ed). Austin, Texas: R.G. Landes Company, 1993, pp 59–72

    Google Scholar 

  10. Stein HJ, Esplugues J, Whittle BJR, Bauernfeind P, Hinder RA, Blum AL: Direct cytotoxic effect of oxgen radicals on the gastric mucosa. Surgery 106:318–324, 1989

    PubMed  Google Scholar 

  11. Del Saldato P, Foschi D, Beboni G, Scarpignato C: Oxygen free radicals interact with indomethacin to cause gastrointestinal injury. Agents Actions 17:484–488, 1985

    Google Scholar 

  12. Pihan G, Regillo C, Szabo S: Free radical and lipid peroxidation in ethanol- or aspirin-induced gastric mucosal injury. Dig Dis Sci 32:1395–1401, 1987

    PubMed  Google Scholar 

  13. Odeleye OE, Eskelson CD, Mufti SI, Watson RR: Vitamin E inhibition of lipid peroxidation and ethanol-mediated promotion of esophageal tumorigenesis. Nutr Cancer 17:223–234, 1992

    PubMed  Google Scholar 

  14. Stein HJ, Hinder RA, Oosthuizen MMJ: Gastric mucosal injury caused by hemorrhagic shock and reperfusion: Protective role of the antioxidant glutathione. Surgery 108:467–474, 1990

    PubMed  Google Scholar 

  15. Bankson DD, Kestin M, Rifai N: Role of free radicals in cancer and atherosclerosis. Clin Lab Med 13:463–480, 1993

    PubMed  Google Scholar 

  16. Lepoivre M, Flaman JM, Henry Y: Early loss of the tyrosyl radical in ribonucleotide reductase of adenocarcinoma cells producing nitric oxide. J Biol Chem 267:22994–23000, 1992

    PubMed  Google Scholar 

  17. Salim AS: The permissive role of oxygen-derived free radicals in the development of colonic cancer in the rat. A new theory for carcinogenesis. Int J Cancer 53:1031–1035, 1993

    PubMed  Google Scholar 

  18. Salim AS: Scavengers of oxygen-derived free radicals prolong survival in advanced colonic cancer. A new approach. Tumour Biol 14:9–17, 1993

    PubMed  Google Scholar 

  19. Keshavarazian A, Zapeda D, List T, Mobarhan S: High levels of reactive oxygen metabolites in colon cancer tissue: Analysis by chemiluminescence. Nutr Cancer 17:243–249, 1992

    PubMed  Google Scholar 

  20. Von Ritter C, Hinder RA, Oosthuizen MMJ, Svensson LG, Hunter SJS, Lambrecht H. Gastric mucosal lesions induced by hemorrhagic shock in baboons. Role of oxygen-derived free radicals. Dig Dis Sci 33:857–864, 1988

    PubMed  Google Scholar 

  21. Smyrk TC: Histology in the diagnosis of foregut disease.In Problems in General Surgery, Tests of Foregul Function. RA Hinder (ed). Philadelphia, Lippincott, 1988, pp 14–38

    Google Scholar 

  22. Adams JD, Lauterburg BH, Mitchell JR: Plasma glutathione and glutathione dissulfide in the rat: Regulation and response to oxidative stress. J Pharmacol Exp Ther 227:749–754, 1983

    PubMed  Google Scholar 

  23. Flohe L, Otting F: Superoxide dismutase assays. Methods Enzymol 105:93–104, 1984

    PubMed  Google Scholar 

  24. Bagchi D, Das DK, Engelman RM, Prasad MR, Subramanian R: Polymorphonuclear leucocytes as potential source of free radicals in the ischaemic-reperfused myocardium. Eur Heart J 1:800–813, 1990

    Google Scholar 

  25. Bagchi M, Hassoun EA, Bagchi D, Stohs SJ: Endrin-induced increases in hepatic lipid peroxidation, membrane microviscosity, and DNA damage in rats. Arch Environ Contam Toxicol 23:1–5, 1992

    PubMed  Google Scholar 

  26. Meister A: Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy. Pharmacol Ther 51:155–194, 1991

    PubMed  Google Scholar 

  27. Stein HJ, Oosthuizen MMJ, Hinder RA, Lamprechts H: Effect of verapamil on hepatic ischemia/reperfusion injury. Am J Surg 165:96–100, 1993

    PubMed  Google Scholar 

  28. Lu SC, Kuhlenkamp J, Robert A, Kaplowitz N: Role of glutathione status in protection against ethanol-induced gastric lesions. Pharmacology 38:57–60, 1989

    PubMed  Google Scholar 

  29. Robert A, Eberle D, Kaplowitz N: Role of glutathione in gastric mucosal cytoprotection. Am J Physiol 247:G296-G304, 1984

    PubMed  Google Scholar 

  30. Coursin DB, Cihla P: The pulmonary effects of buthionine sulfoximine treatment and glutathione depletion in rats. Am Rev Respir Dis 138:1471–1479, 1988

    PubMed  Google Scholar 

  31. Ookhtens M, Hobdy K, Corvasce MC, Aw TY, Kaplowitz N: Sinusoidal efflux of glutathione in the perfused rat liver: Evidence for a carrier-mediated process. J Clin Invest 75:258–265, 1985

    PubMed  Google Scholar 

  32. Buckley BJ, Kent RS, Whorton A: Regulation of endothelial cell prostaglandine synthesis by glutathione. J Biol Chem 266:16659–16666, 1991

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Surgery, Pharmacology and Biomedical Sciences, Creighton University, 68131, Omaha, Nebraska

    Gerold J. Wetscher MD, Galen Perdikis MD, David H. Kretchmar PhD, Ronald G. Stinson MD, Debasis Bagchi PhD, Elizabeth J. Redmond FRCS, Thomas E. Adrian PhD &  Ronald A. Hinder MD, PhD, FACS

  2. 2nd Department of Surgery, University of Innsbruck, Innsbruck, Austria

    Gerold J. Wetscher MD, Galen Perdikis MD, David H. Kretchmar PhD, Ronald G. Stinson MD, Debasis Bagchi PhD, Elizabeth J. Redmond FRCS, Thomas E. Adrian PhD &  Ronald A. Hinder MD, PhD, FACS

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  1. Gerold J. Wetscher MD
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  2. Galen Perdikis MD
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  3. David H. Kretchmar PhD
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  4. Ronald G. Stinson MD
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  5. Debasis Bagchi PhD
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  6. Elizabeth J. Redmond FRCS
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  7. Thomas E. Adrian PhD
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  8. Ronald A. Hinder MD, PhD, FACS
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Wetscher, G.J., Perdikis, G., Kretchmar, D.H. et al. Esophagitis in sprague-dawley rats is mediated by free radicals. Digest Dis Sci 40, 1297–1305 (1995). https://doi.org/10.1007/BF02065542

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  • DOI: https://doi.org/10.1007/BF02065542

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