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L-glutamine enemas attenuate mucosal injury in experimental colitis

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Diseases of the Colon & Rectum

Abstract

PURPOSE: The aim of this study was to investigate the role of I-glutamine, short chain fatty acid, prednisolone, and mesalazine (5-aminosalicylic acid) enemas on mucosal damage and inflammation in experimental colitis. METHODS: Colitis was induced in rats with trinitrobenzene sulfonic acid in ethanol. Saline (n=14), prednisolone (n=13), 5-aminosalicylic acid (n=14), I-glutamine (n=14), and short chain fatty acid (n=13) enemas were applied twice daily to the rats for seven days after the induction of colitis. The sham group (n=9) received only saline enemas. Rats were killed at the seventh day and their colonic macroscopic inflammatory scores were determined. Colonic mucosal gamma glutamyl transpeptidase activity and colonic mucosal malondialdehyde levels were measured. The same measurements but no enemas were done in the control group (n=7). RESULTS: There were significant differences in macroscopic inflammatory scores between sham and colitis groups (P<0.001). The macroscopic inflammatory scores of the colitis group were higher than the short chain fatty acid and glutamine groups (P<0.05). Whereas the mucosal gamma glutamyl transpeptidase activity was diminished in prednisolone, 5-aminosalicylic acid, and short chain fatty acid groups when compared with the control group; in the colitis, sham, and glutamine groups the activity of this enzyme did not change. The mucosal malondialdehyde levels were significantly lower in the prednisolone and glutamine groups than in the colitis group. CONCLUSION: Only one of four agents tested, namely, I-glutamine enemas, could decrease the severity of colitis both morphologically and biochemically. Moreover, L-glutamine prevented the colitis-induced oxidant injury in the colonic mucosa. On the other hand, prednisolone and short chain fatty acids seemed to improve only the physiologic changes of colitis.

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References

  1. Roediger WE. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet 1980;4:712–5.

    Google Scholar 

  2. Evans MA, Shronts EP. Intestinal fuels: glutamine, short chain fatty acids, and dietary fiber. J Am Diet Assoc 1992;92:1239–46.

    Google Scholar 

  3. Cummings JH. Short chain fatty acids in the human colon. Gut 1981;22:763–79.

    Google Scholar 

  4. Mortensen FV, Hessov I, Birke H, Korsgoard N, Nielsen H. Micro-circulatory and trophic effects of short chain fatty acids in the human rectum after Hartman's procedure. Br J Surg 1991;78:1208–11.

    Google Scholar 

  5. Ambroze WL Jr, Pemberton JH, Phillips SF, Bell AM, Haddad AC. Fecal short-chain fatty acid concentrations and effect on ileal pouch function. Dis Colon Rectum 1993;36:235–9.

    Google Scholar 

  6. Senagore AJ, MacKeigan JM, Scheider M, Ebrom JS. Short-chain fatty acid enemas: a cost-effective alternative in the treatment of nonspecific proctosigmoiditis. Dis Colon Rectum 1992;35:923–7.

    Google Scholar 

  7. Friedel D, Levine GM. Effect of short chain fatty acids on colonic function and structure. JPEN 1992;16:1–4.

    Google Scholar 

  8. Breuer RI, Buto SK, Christ ML,et al. Rectal irrigation with short chain fatty acids for distal ulcerative colitis. Dig Dis Sci 1991;36:185–7.

    Google Scholar 

  9. Steinhart AH, Brzezinsky A, Baker JP. Treatment of refractory proctosigmoiditis with butyrate enemas. Am J Gastroenterol 1994;89:179–83.

    Google Scholar 

  10. Scheppach W, Sommer H, Kirchner T,et al. Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology 1992;103:51–6.

    Google Scholar 

  11. Hartmann F, Plauth M. Intestinal glutamine metabolism. Metabolism 1989;38(Suppl 8):18–24.

    Google Scholar 

  12. Fujita T, Sakurai K. Efficacy of glutamine-enriched enteral nutrition in an experimental model of mucosal ulcerative colitis. Br J Surg 1995;82:749–51.

    Google Scholar 

  13. Harris ML, Schiller HJ, Reilly PM, Donowitz M, Grisham MB, Bulkley GB. Free radicals and other reactive oxygen metabolites in inflammatory bowel disease: cause, consequence or epiphenomenon? Pharmacol Ther 1992;53:375–408.

    Google Scholar 

  14. Simmonds NJ, Rampton DS. Inflammatory bowel disease—a radical view. Gut 1993;34:865–8.

    Google Scholar 

  15. Salim AS. Role of oxygen-derived free radical scavengers in the management of recurrent attacks of ulcerative colitis: a new approach. J Lab Clin Med 1992;19:710–7.

    Google Scholar 

  16. Babbs CF. Oxygen radicals in ulcerative colitis. Free Radic Biol Med 1992;13:169–81.

    Google Scholar 

  17. Nakamura K, Sugai T, Kinoshita N, Scato M, Taniguchi S, Kawase S. Effect of mesalazine, an agent for treatment of idiopathic inflammatory bowel disease, on reactive oxygen metabolites and LTB4 formation. Nippon Yakurigaku Zasshi 1994;104:447–57.

    Google Scholar 

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

    Google Scholar 

  19. Vilaseca J, Salas A, Guarner F, Rodinguez R, Martinez M, Malagelada JR. Dietary fish oil reduces progression of chronic inflammatory lesions in rat model of granulomatous colitis. Gut 1990;31:539–44.

    Google Scholar 

  20. Rosalki SB, Rau D, Lehmann D, Prentice M. Determination of serum gamma glutamyl transpeptidase activity and its clinical applications. Ann Biol Chem 1970;7:143–46.

    Google Scholar 

  21. Rosalki SB. Gamma glutamyl transpeptidase. Adv Clin Chem 1975;17:53–107.

    Google Scholar 

  22. Ohkava H, Ohihi N, Yagi K. Assay for lipid peroxides in animals tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–8.

    Google Scholar 

  23. Lowry GH, Roselbrough NJ, Farr AL, Randall RJ. Protein measurement with the folin reagent. J Biol Chem 1951;193:265–75.

    Google Scholar 

  24. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 1989;96:795–803.

    Google Scholar 

  25. Grisham MB, Wolkmer C, Tso P, Yamada T. Metabolism of trinitrobenzene sulphonic acid by the rat colon produces oxygen species. Gastroenterology 1991;101:540–7.

    Google Scholar 

  26. Gardiner KR, Anderson NH, McCaigue MD, Erwin PJ, Halliday MI, Rowlands BJ. Adsorbents as antiendotoxin agents in experimental colitis. Gut 1993;34:51–5.

    Google Scholar 

  27. Gardiner KR, Anderson NH, Rowlands BJ, Barbul A. Colitis and colonic mucosal barrier dysfunction. Gut 1995;37:530–5.

    Google Scholar 

  28. Salman T, Güvenç H, Koçer H,et al. Fetal intestinal transplantation: use of immunosuppressive agent syngenetic hosts. Pediatr Surg 1989 3:94–9:

    Google Scholar 

  29. Bengmark S, Jeppson B. Gastrointestinal surface protection and mucosa reconditioning. JPEN 1995;19:410–5.

    Google Scholar 

  30. De Meyts ER, Chang MS, Robison CT, Groffers J, Heisterkamp N, Forman H. Transfection with gamma glutamyl transpeptidase enhances recovery from glutathione depletion using extracellular glutathione. Toxicol Appl Pharmacol 1992;114:56–62.

    Google Scholar 

  31. Steacker JL, Sattler CA, Pitot HC. Sodium butyrate preserves aspects of the differentiated phenotype of normal adult rat hepatocytes culture. J Cell Physiol 1988;135:367–76.

    Google Scholar 

  32. Hertz F, Cloarec A. Pharmacology of free radicals: recent views on their relation to inflammatory mechanisms. Life Sci 1984;34:713–20.

    Google Scholar 

  33. Sharon P, Stenson WF. Metabolism of arachidonic acid in acetic acid colitis in rats. Gastroenterology 1985;88:55–63.

    Google Scholar 

  34. Burakoff R, Zhao L, Joseph I, Koo H, Rosenfeld W. SOD prevents colitis and attenuates eicosanoid release and motility changes in a trinitrobenzene sulphonic acid rabbit colitis [abstract]. Gastroenterology 1991;100:A565.

    Google Scholar 

  35. Ondrula D, Nelson RL, Andrianopoulos G,et al. Quantitative determination of pentane in exhaled air correlates with colonic inflammation in the rat colitis model. Dis Colon Rectum 1993;36:457–62.

    Google Scholar 

  36. Karmeli F, Eliakim R, Okon E, Samuni A, Rachmilweitz D. A stable nitroxide radical effectively decreased mucosal damage in experimental colitis. Gut 1995;37:386–93.

    Google Scholar 

  37. Bhaskar L, Ramakrishma BS, Balasubrammanian KA. Colonic mucosal antioxidant enzyme and lipid peroxide levels in normal subjects and patients with ulcerative colitis. J Gastroenterol Hepatol 1995;10:208–29.

    Google Scholar 

  38. Donowitz M. Arachidonic acid metabolites and their role in inflammatory bowel disease. Gastroenterology 1985;88:530–7.

    Google Scholar 

  39. Zijlstra FJ, Van Dijk JP, Wilson JH. Increased platelet activating factor synthesis in experimental colitis after diclofenac and 5-amino-salicylic acid. Eur J Pharmacol 1993;249:R1–2.

    Google Scholar 

  40. Nielsen OH, Bouchelouche PN, Berild D, Ronne IA. Effect of 5-aminosalicylic acid and analogue substances on superoxide generation and intracellular free calcium in human neutrophilic granulocytes. Scand J Gastroenterol 1993;28:527–32.

    Google Scholar 

  41. Sutherland LR, Martin F, Greer S,et al. 5-aminosalicyclic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis and pouchitis. Gastroenterology 1987;92:1894–8.

    Google Scholar 

  42. Roediger WE. Utilisation of nutrients by isolated epithelial cells of the rat colon. Gastroenterology 1982;83:424–9.

    Google Scholar 

  43. Scheppach W, Bartram P, Richter A,et al. Effect of short chain fatty acids on the human colonic mucosa in vitro. JPEN 1992;16:43–8.

    Google Scholar 

  44. Mortensen FV, Nielsen H, Mulvany MJ, Hessov I. Short chain fatty acids dilate isolated human colonic resistance arteries. Gut 1990;31:1391–9.

    Google Scholar 

  45. Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 1987;28:1221–7.

    Google Scholar 

  46. Frankel WL, Zhang W, Singh A,et al. Mediation of the trophic effects of short-chain fatty acids on the rat jejunum and colon. Gastroenterology 1994;106:375–80.

    Google Scholar 

  47. Grimble G. Fibre, fermentation, flora and flatus. Gut 1989;30:6–13.

    Google Scholar 

  48. Chapman MA, Grahn MF, Boyle MA, Hutton M, Rogers J, Williams NS. Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis. Gut 1994;35:73–6.

    Google Scholar 

  49. Chapman MA, Grahn MF, Hutton M, Willams NS. Butyrate metabolism in the terminal ileal mucosa of patients with ulcerative colitis. Br J Surg 1995;82:36–8.

    Google Scholar 

  50. Finnie IA, Taylor BA, Rhodes JM. Ileal and colonic epithelial metabolism in quiescent ulcerative colitis: increased glutamine metabolism in distal colon but no defect in butyrate metabolism. Gut 1993;34:1552–6.

    Google Scholar 

  51. Finnie IA, Dwarakanath AD, Taylor BA, Rhodes JM. Colonic mucin synthesis is increased by sodium butyrate. Gut 1995;36:93–9.

    Google Scholar 

  52. Rombeau JL, Kripke SA. Metabolic and intestinal effect of short chain fatty acids. JPEN 1990;14(Suppl):S181–5.

    Google Scholar 

  53. Breuger RI, Soergel KH, Lashner BA,et al. Short chain fatty acid rectal irrigation for left-sided ulcerative colitis: a randomised, placebo controlled trial. Gut 1997;40:485–91.

    Google Scholar 

  54. Ko TC, Beauchimp RD, Townsend CM, Thompson JC. Glutamine is essential for epidermal growth factor-stimulated intestinal cell proliferation. Surgery 1993;114:147–54.

    Google Scholar 

  55. Hong RW, Rounds JD, Helton WS, Robinson MK, Wilmore DW. Glutamine preserves liver glutathione after lethal hepatic injury. Ann Surg 1992;215:114–9.

    Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Uluddg University School of Medicine, Bursa, Turkey

    Esma Sürmen Gür M.D.

  2. Department of Pathology, Uludag University School of Medicine, Bursa, Turkey

    Ahmet Bayer M.D.

  3. Department of Surgery, Uludag University Medical School, 16059, Bursa, Turkey

    Ekrem Kaya M.D., Halil Özgüç M.D. &  Rifat Tokyay M.D., M.M.S.

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  1. Ekrem Kaya M.D.
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  2. Esma Sürmen Gür M.D.
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Supported by The Scientific and Technical Research Council of Turkey.

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Kaya, E., Gür, E.S., Özgüç, H. et al. L-glutamine enemas attenuate mucosal injury in experimental colitis. Dis Colon Rectum 42, 1209–1215 (1999). https://doi.org/10.1007/BF02238577

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