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Bombesin Ameliorates Colonic Damage in Experimental Colitis

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Abstract

In the present study we investigated thepossible therapeutic effects of bombesin on anexperimentally induced colitis model in rats.Inflammation of the colon was induced by a singleintracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid(TNBS) at 8 cm from the anus. Immediately after theinduction of colitis, some rats were given bombesin (10μg/kg; subcutaneously) three times a day for 14 days, while another group received vehicletreatment. On day 14, the rats were decapitated andplasma carbonyl content and tissue myeloperoxidaselevel, as an index of granulocyte infiltration intointestinal tissue, were determined in order to obtain anobjective evaluation of colonic injury. In the colitisgroup, increased macroscopic damage score, elevated MPOlevel and high plasma carbonyl content, together with the microscopic appearance revealed severeinflammatory changes resembling IBD. Bombesin treatmentattenuated the TNBS-induced colonic damage andstimulated histopathologically apparent mucosalproliferation, suggesting that bombesin may play a role inprotecting gut integrity.

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REFERENCES

  1. Kirsner J, Shorter RG: Recent developments in “nonspecific” inflammatory bowel disease. N Engl J Med 306:775–779, 1982

    Google Scholar 

  2. Fretland DJ, Djuric SW, Gaginella TS: Eicosanoids and inflammatory bowel disease: Regulation and prospects for therapy. Prostaglandins Leukot Essent Fatty Acids 41:215–233,1990

    Google Scholar 

  3. Rachmilewitz D, Karmeli F, Okon E: Sulfhydryl blockerinduced rat colonic inflammation is ameliorated by inhibition of nitric oxide synthase. Gastroenterology 109:98–106, 1995

    Google Scholar 

  4. Ligumsky M, Simon PL, Karmeli F, Rachmilewitz D: Role of interleukin 1 in inflammatory bowel disease: Enhanced production during active disease. Gut 31:686–689, 1990

    Google Scholar 

  5. Spindel ER, Giladi E, Segerson TP, Nagalla S: Bombesin-like peptides: of ligands and receptors. Recent Prog Horm Res 48:365–391, 1993

    Google Scholar 

  6. Goodlad RA, Wright NA: Peptides and epithelial growth regulation. Experientia Suppl 56:180–191, 1989

    Google Scholar 

  7. Greeley GH Jr, Newman J: Enteric bombesin-like peptides. In Gastrointestinal Endocrinology. JC Thompson, GH Greeley Jr, PL Rayford, CM Townsend Jr (eds). New York, McGraw-Hill, 1987, pp 322–329

    Google Scholar 

  8. Espamer V, Melchiorri P: Actions of bombesin on se cretions and motility of the gastrointestinal tract. In Gastrointestinal Hormones. JC Thompson (ed). Austin, University of Texas Press, 1975, pp 575–589

    Google Scholar 

  9. Lehy T, Puccio F: Inflcuence of bombesin on gastrointestinal and pancreatic cell growth in adult and suckling animals. Ann NY Acad Sci 547:255–267, 1988

    Google Scholar 

  10. Evers BM, Izukura M, Townsend CM Jr, Uchida T, Thompson JC: Differential effects of gut hormones on pancreatic and intestinal growth during administration of an elemental diet. Ann Surg 211:630–636, 1990

    Google Scholar 

  11. Johnson LR, Guthrie PD: Regulation of antral gastrin content. Am J Physiol 245:G725-G729, 1983

    Google Scholar 

  12. Chu KU, Higashide S, Evers BM, Rajamaran S, Ishizuka J, Townsend CM, Thompson JC: Bombesin improves survival from methotrexate-induced enterocolitis. Ann Surg 220:570–577, 1994

    Google Scholar 

  13. Koch TK, Carney JA, Go VLW: Distribution and quantitation of gut neuropeptides in normal intestine and inflammatory bowel diseases. Dig Dis Sci 32:369–376, 1987

    Google Scholar 

  14. Poitras P, Tasse D, Laprise P: Stimulation of motilinre lease by bombesin in dogs. Am J Physiol 245:G249-G256, 1983

    Google Scholar 

  15. Morris GP, Beck PL, Henidge MS, Depew WT, Szewcuk MR, Wallace JL: Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 97:326–337,1989

    Google Scholar 

  16. Monnikes H, Schmidt BG, Raybould HE, Taché Y: CRF in the paraventricular nucleus mediates gastric and colonic motor response to restraint stress. Am J Physiol 262:G137-G143,1992

    Google Scholar 

  17. Miller MS, Galligan JJ, Burks TF: Accurate me asurement of intestinal transit in the rat. J Pharmacol Methods 6:211–217,1981

    Google Scholar 

  18. Wallace JL, MacNaughton WK, Morris GP, Beck PL: Inhibition of leukotriene synthesis markedly accelerates healing in a rat model of inflammatory bowel disease. Gastroenterology 96:29–36, 1989

    Google Scholar 

  19. Kurtel H, Granger DN, Tso P, Grisham MB: Vulnerability of intestinal interstitial fluid to oxidant stress. Am J Physiol 263:G573-G578, 1992

    Google Scholar 

  20. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER: Determination of carbonyl content in oxidative ly modified proteins. Methods Enzymol 186:464–478, 1990

    Google Scholar 

  21. Krawisz JE, Sharon P, Stenson WF: Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology 87:1344–1350, 1984

    Google Scholar 

  22. Grisham MB, Benoit JN, Granger DN: Assessment of leukocyte involvement during ischemia and reperfusion of intestine. Methods Enzymol 186:729–742, 1990

    Google Scholar 

  23. Elson CO, Sartor RB, Tennyson GS, Riddell RH: Experimental models of inflammatory bowel disease. Gastroenterology 109:1344–1367, 1995

    Google Scholar 

  24. Gue M, Bonbonne C, Fioramonti J, More J, Del Rio-Lacheze C, Comera C, Bueno L: Stress-induced enhancement of colitis in rats: CRF and arginine vasopressin are not involved. Am J Physiol 272:84–91, 1997

    Google Scholar 

  25. Kreo CJ, Gores A, Go VLW: Gastrointestinal regulatory peptides modulate mouse lymphocyte functions under serum-free conditions in vitro. Immunol Invest 15:103–111, 1986

    Google Scholar 

  26. Li J, Kudsk KA, Hamidian M, Gocinski BL: Bombesin affects mucosal immunity and gut-associated lymphoid tissue in intravenously fed mice. Arch Surg 130:1164–1169, 1995

    Google Scholar 

  27. Chu KU, Evers BM, Ishizuka J, Townsend CM, Thompson JC: Role of bombesin on gut mucosal growth. Ann Surg 222:94–100, 1995

    Google Scholar 

  28. Porreca F, Burks TF, Koslo RJ: Centrally-mediated bombe sin effects on gastrointestinal motility. Life Sci 37:125–134, 1985

    Google Scholar 

  29. Moran TH, Moody TW, Hostetler AM, Robinson PH, Goldrich M, McHugh PR: Distribution of bombesin binding sites in the rat gastrointestinal tract. Peptides 9:643–649, 1988

    Google Scholar 

  30. Polak JM, Ghatei MA, Wharton J, Bishop AE, Bloom SR, Solcia E, Brown MR, Pearse AGE: Bombesin-like immunore-activity in the gastrointestinal tract, lung, and central nervous system. Scand J Gastroente rol 49:148, 1978

    Google Scholar 

  31. Puccio F, Lehy T: Bombesin ingestion stimulates epithelial digestive cell proliferation in suckling rats. Am J Physiol 256:G328-G334, 1989

    Google Scholar 

  32. Sagor GR, Ghatel MA, O'shaughnessy DJ, Al-Mukhtar MYT, Wright NA, Bloom SR: Influence of somatostatin and bombesin on plasma enteroglucagon and cell proliferation after intestinal resection in the rat. Gut 26:89–94, 1985

    Google Scholar 

  33. Solomon TE, Petersen H, Elashoff J, Grossman MI: Interaction of caerule in and secretin on pancreatic size and composition in rat. Am J Physiol 235:E714-E719, 1978

    Google Scholar 

  34. Feurle GE, Muller B, Ohnheiser G, Bama I: Action of neurotensin on size, composition, and growth of pancreas and stomach in the rat. Regul Pept 13:53–62, 1985

    Google Scholar 

  35. Greenberg GR, Mitznegg P, Bloom SR: Effect of pancreatic polypeptide on DNA synthesis in the pancreas. Experientia33:1332–1333, 1977

    Google Scholar 

  36. Johnson LR: New aspects of the trophic action of gastrointestinal hormones. Gastroenterology 72:788–792, 1977

    Google Scholar 

  37. Sharon P, Ligumsky M, Rachmilewitz D, Zor U: Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine. Gastroenterology 75:638–640, 1978

    Google Scholar 

  38. Allgayer H, Deschryver K, Stenson WF: Treatment with16,169-dimethyl prostaglandin-E2 before and after induction of colitis with trinitrobenzene sulfonic acid in rats decreases inflammation. Gastroenterology 96:1290–1300, 1989

    Google Scholar 

  39. Millar JBA, Rozengurt E: Arachidonic acid release by bombesin. A nove l postreceptor target for heterologous mitogenic desensitization. J Biol Chem 265:19973–19979, 1990

    Google Scholar 

  40. Soder O, Hellstrom PM: Neuropeptide regulation of human thymocyte, guinea pig T lymphocyte and rat B lymphocyte mitogenesis. Int Arch Allergy Appl Immunol 12:325–331, 1987

    Google Scholar 

  41. Jin GF, Guo YS, Houston CW: Bombesin: An activator of specific Aeromonas antibody secretion in rat intestine. Dig Dis Sci 34:1708–1712, 1989

    Google Scholar 

  42. Van Tol EAF, Elzo Kraemer CV, Verspaget HW, Masclee AdAM, Lamers CBHW: Intravenous administration of bombesin in man stimulates natural killer cell activity against tumour cells. Neuropeptides 18:15–21, 1991

    Google Scholar 

  43. Bienenstock J, Perdue M, Stainsz A, Stead R: Neurohormonal regulation of gastrointe stinal immunity. Gastroenterology 93:1431–1434, 1987

    Google Scholar 

  44. Bitar KN, Kaminski MS, Hailat N, Cease KB, Strahler JR: HSP27 is a mediator of sustained smooth muscle contraction in response to bombe sin. Biochem Biophys Res Commun 181:1192–1200, 1991

    Google Scholar 

  45. Bitar KN, Zhu X: Expression of bombesin-receptor subtypes and their differential regulation of colonic smooth muscle contraction. Gastroenterology 105:1672–1680, 1993

    Google Scholar 

  46. Barone FC, Joslyn AF, Schwartz LW, Fondacaro JD, Wasserman MA, Rachmilewitz D: Increased colonic motility in rodent experimental colitis. Gastroenterology 94:A24, 1988

    Google Scholar 

  47. Pons L, Droy-Lefaix MT, Bueno L: Leukotriene D4 participates in colonic transit disturbances induced by intracolonic administration of trinitrobenzene sulfonic acid in rats. Gastroenterology 102:149–156, 1992

    Google Scholar 

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Authors
  1. Bahadir M. Gulluoglu
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  2. Hizir Kurtel
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  3. Mine G. Gulluoglu
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  4. A. Ozdemir Aktan
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  5. Cumhur Yegen
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  6. Ferhunde Dizdaroglu
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  7. Rifat Yalin
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  8. Berrak C. Yegen
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Gulluoglu, B.M., Kurtel, H., Gulluoglu, M.G. et al. Bombesin Ameliorates Colonic Damage in Experimental Colitis. Dig Dis Sci 44, 1531–1538 (1999). https://doi.org/10.1023/A:1026646523284

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