Skip to main content
Log in

Pathways Involved in Mild Gastrointestinal Inflammation Induced by a Low Level Exposure to a Food Contaminant

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Chronic gut inflammation is associated with radical oxygen species (ROS) genesis. ROS may activate certain transcription factors such as nuclear factor κ beta (NF-κB), which regulates cyclooxygenase-2 (COX-2). Diquat, a food contaminant, is responsible for oxidative stress. This work aimed to establish the involvement of ROS and prostanoids on diquat-induced gastrointestinal inflammation and mast cell hyperplasia. Diquat increased gastrointestinal MPO activity and mast cell number. Its effect on gastric MPO activity was reversed by PD 138,387 (a COX-2 selective inhibitor) and PDTC (an inhibitor of NF-κB activation) but not by DMSO (a hydroxyl radical scavenger) and allopurinol (a xanthine oxidase inhibitor). In contrast, increased jejunal MPO activity was blocked by both DMSO, PD 138,387, and PDTC, while allopurinol enhanced it. PD 138,387 and PDTC reduced gastrointestinal mast cell number while DMSO and allopurinol did not Diquat-induced inflammation involves a gastrointestinal NF-κB activation and COX-2 dependent proinflammatory prostanoid synthesis. Furthermore, the hydroxyl radical is involved in intestinal but not gastric inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Nakajima S, Krishnan B, Ota H, Segura M, Hattori T, Graham D, Genta M: Mast cell involvement in gastritis with or without Helicobacter pylori infection. Gastroenterology 113:746–754, 1997

    PubMed  Google Scholar 

  2. Geboes K, Ecors N: The infectious track in inflammatory bowel disease: a controversial area. Res Clin Forums 00:41–48, 1995

    Google Scholar 

  3. Satsangi J, Jewellin DP, Rosenberg WMC, Bell JI: Genetics of inflammatory bowel disease. Gut 35:696–700, 1994

    PubMed  Google Scholar 

  4. Bing XIA, Crosuis JBA. Meuwissen SGM, Pena AS: Inflammatory bowel disease: Definition, epidemiology, etiologic aspects, and immunogenetic studies. World J Gastroenterol 4:446–458, 1998

    PubMed  Google Scholar 

  5. Anton PM, Theodorou V, Bertrand V, Eutamene H, Aussenac T, Feyt N, Fioramonti J, Bueno L: Chronic ingestion of a potential food contaminant induces gastrointestinal inflammation in rats: Role of nitric oxide and mast cells. Dig Dis Sci 45:1842–1849, 2000

    PubMed  Google Scholar 

  6. Crabtree HC, Lock EA, Rose MS: Effects of diquat on the gastrointestinal tract of rats. Toxicol Appl Pharmacol 41:585–595, 1977

    PubMed  Google Scholar 

  7. Thomas CE, Aust SD: Reductive release of iron from ferritin by cation free radicals of paraquat and other bipyridils. J Biol Chem 265:13064–13070, 1986

    Google Scholar 

  8. Farrington JA, Ebert M, Land EJ, Fletcher K: Bipyridilum quaternary salts and related compounds. V. Pulse radiolysis studies of the reaction of paraquat radical with oxygen. Implication for the mode of action of bipyridil herbicides. Biochem Biophys Acta 314:372–381, 1973

    PubMed  Google Scholar 

  9. Bus JS, Cagen SZ, Olgaard M, Gibson JE: A mechanism of paraquat toxicity in mice and rats. Toxicol Appl Pharmacol 35:501–513, 1976

    PubMed  Google Scholar 

  10. McCord JM: Free radicals and inflammation: Protection of synovial fluid by superoxide dismutase. Science 185:529–531, 1974

    PubMed  Google Scholar 

  11. Grisham MB: Oxidants and free radicals in inflammatory bowel disease. Lancet. 344:859–861, 1994

    PubMed  Google Scholar 

  12. Jourd'heuil D, Morise Z, Conner EM, Kurose I, Grisham MB: Oxidant-regulation of gene expression in the chronically inflamed intestine. Keio J Med 46:10–15, 1997

    PubMed  Google Scholar 

  13. Grisham MB, Granger DN: Neutrophil-mediated mucosal injury. Role of reactive oxygen metabolites. Dig Dis Sci 33:6S–15S, 1988

    Google Scholar 

  14. Baeurle PA, Henkel T: Function and activation of NK-?B in the immune system. Annu Rev Immunol 12:141–179, 1994

    PubMed  Google Scholar 

  15. May MJ, Ghosh S: Signal transduction through NF-?B. Immunol Today 19:80–88, 1998

    PubMed  Google Scholar 

  16. Arai I, Hamasaka Y, Futaki S, Takahashi S, Yoshikawa K, Higuchi S, Otomo S: Effect of NS-398, a new nonsteroidal antiinflammatory agant, on gastric ulceration and acid secretion in rats. Res Commun Chem Pathol Pharmacol 81:259–270, 1993

    PubMed  Google Scholar 

  17. Chan CC, Boyce S, Brideau C, Ford-Hutchinson AW, Gordon R, Guay D, Hill RG, Li CS, Mancini J, Penneton M, Prasit P, Rasori R, Riendeau D, Roy P, Tagari P, Vickers P, Wong E, Rodger IW: Pharmacology of a selective cyclooxygenase-2 inhibitor L-245,337: A novel nonsteroidal antiinflammatory agent with an ulcerogenic sparing effect in rat and nonhuman primate stomach. J Pharmacol Exp Ther 274:1531–1537, 1995

    PubMed  Google Scholar 

  18. Lesch CA, Gilbertsen RB, Song Y, Dyer RD, Schrier D, Kraus ER, Sanchez B, Guglietta A: Effects of novel anti-inflammatory compounds on healing of acetic acid-induced gastric ulcer in rats. J Pharmacol Exp Ther 287:301–306, 1998

    PubMed  Google Scholar 

  19. Bradley PP, Priebat DA, Christensen RD, Rothstein G: Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206–209, 1982

    PubMed  Google Scholar 

  20. Robberts ISD, Jones CJP, Stoddart RW: Lectin histochemistry of the mast cell: heterogeneity of rodent and human mast cell population. Histochem J 22:73–80, 1990

    PubMed  Google Scholar 

  21. Parks DA, Granger DN: Ischemia-induced vascular changes: role of xanthine oxidase and hydroxyl radicals. Am J Physiol 245:G285–G289, 1983

    PubMed  Google Scholar 

  22. Onyeama HP, Oehme FW: A litterature review of paraquat toxicity. Vet Hum Toxicol 26:494–502, 1984

    PubMed  Google Scholar 

  23. Drake IM, Mapstone NP, Schorah CJ, White KLM, Chalmers, DM, Dixon MF, Axon ATR: Reactive oxygen species activity and lipid peroxidation in Helicobacter pylori associated gastritis: Relation to gastric mucosal ascorbic acid concentrations and effect of H. pylori eradication. Gut 42:768–771, 1998.

    PubMed  Google Scholar 

  24. Keshavarzian A, Sedghi S, Kanofsky J, List T, Robinson C, Ibrahim C, Winship D: Excessive production of reactive oxygen metabolites by inflamed colon: Analysis by chemiluminescence probe. Gastroenterology 103:177–185, 1992

    PubMed  Google Scholar 

  25. Salvemini D, Wang ZQ, Stern MK, Currie MG, Misko TP: Peroxynitrite decomposition catalysts: Therapeutics for peroxynitrite-mediated pathology. Proc Natl Acad Sci USA 95:2659–2663, 1998

    PubMed  Google Scholar 

  26. Qu XW, Rozenfeld RA, Huang W, Bulkley GB, Hsueh W: The role of xanthine oxidase in platelet activating factor induced intestinal injury in the rat. Gut 44:203–211, 1999

    PubMed  Google Scholar 

  27. Perry MA, Wadhwa S, Parks DA, Pickard W, Granger DN: Role of oxygen radicals in ischemia-induced lesions in the cat stomach. Gastroenterology 90:362–367, 1986

    PubMed  Google Scholar 

  28. Radi R, Beckman JS, Bush KM, Freeman BA: Peroxinitriteinduced membrane lipid peroxidation: The cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 288:481–487, 1991

    PubMed  Google Scholar 

  29. Naito Y, Yoshikawa T, Matsuyama K, Nishimura S, Yagi N, Kondo M: Effects of free radical scavengers on indomethacininduced aggravation of gastric ulcer in rats. Dig Dis Sci 40:2019–2021, 1995

    PubMed  Google Scholar 

  30. Moyana T, Lalonde JM: Carrageenan-induced intestinal injury: possible role of oxygen free radicals. Ann Clin Lab Sci 21:258–263, 1991

    PubMed  Google Scholar 

  31. Sandhu IS, Grisham MB: Modulation of neutrophil function as a mode of therapy for gastrointestinal inflammation. In Immunopharmacology of the Gastrointestinal Tract. JL Wallace (ed). Toronto, Academic Press, 1993, pp 51–68

    Google Scholar 

  32. Granger DN, McCord JM, Parks DA: Xanthine oxidase inhibitors attenuate ischemia-induced vascular parmeability changes in the cat intestine. Gastroenterology 90:80–84, 1986

    PubMed  Google Scholar 

  33. Denburg JA: Basophil and mast cell lineage in vitro and in vivo. Blood 79:846–860, 1992

    PubMed  Google Scholar 

  34. Heller A, koch T, Schmeck J, van Ackern K: Lipid mediators in inflammatory disorders. Drugs 56:487–496, 1999

    Google Scholar 

  35. Simmons DL, Xie W, Chipman JG, Evett GE: Multiple cyclooxygenases: Cloning of a mitogen-inducible form. In Pros-taglandins, Leukotrienes, Lipoxins and PAF. JM Bailey (ed). New York, Plenum Press, 1991, pp 67–78

    Google Scholar 

  36. Smith WL: Prostanoid biosynthesis and mechanisms of action. Am J Physiol 263:F181–F191, 1992

    PubMed  Google Scholar 

  37. D'Aquisto F, Ialenti A, Iuvone T, Di Rosa, M, Carnuccio R: Inhibition of nuclear factor-?B prevents the loss of vascular tone in lipopolysaccharide-treated rats. Eur J Pharmacol 363:253–257, 1999

    Google Scholar 

  38. Rogler G, Brand K, Vogl D, Page S, Hofmeister R, Andus T, Knuechel R., Baeurle PA, Sholmerich J, Gross V: Nuclear factor ?B is activated in macrophages and epithelial cells of inflamed intestinal mucosa. Gastroenterology 115:357–369, 1998

    PubMed  Google Scholar 

  39. Schreiber S, Nikolaus S, Hampe J: Activation of nuclear factor ?B in inflammatory bowel disease. Gut 42:477–484, 1998

    PubMed  Google Scholar 

  40. Morrow JD, Hill KE, Burk RF, Nanmour TM, Badr KF: A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical catalyzed mechanism. Proc Natl Acad Sci USA 87:9383–9387, 1990

    PubMed  Google Scholar 

  41. Barrera S, Lai J, Fiocchi C, Roche JK: 1996. Regulation by prostaglandin E2 of intereukin release by T lymphocytes in mucosa. J Cell Physiol 166:130–137, 1996

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anton, P.M., Theodorou, V., Roy, S. et al. Pathways Involved in Mild Gastrointestinal Inflammation Induced by a Low Level Exposure to a Food Contaminant. Dig Dis Sci 47, 1308–1315 (2002). https://doi.org/10.1023/A:1015322514547

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015322514547

Navigation