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The effect of heme oxygenase-1 induction by glutamine on TNBS-induced colitis

The effect of glutamine on TNBS colitis

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Abstract

Background

Inflammatory bowel disease is a multifactorial inflammatory disease of the colon and rectum with an unknown etiology. In the present study, we aimed to investigate whether heme oxygenase-1 (HO-1) induction by glutamine could protect colitis-induced damage from oxidative, inflammatory, and apoptotic damage.

Method

The rats were divided into four groups. Group 1 had TNBS colitis alone, group 2 had TNBS-induced colitis and glutamine 1 g/kg/day intragastric gavage for 3 days before TNBS solution administration and 15 days following TNBS solution administration, group 3 had glutamine alone 1 g/kg/day intragastric gavage for 18 days before being killed, and group 4 had isotonic saline solution alone 1 cm3/rat intragastric gavage for 18 days before being killed. Colonic malondialdehyde (MDA) levels, glutathione (GSH) levels, caspase-3 activities, and HO-1 expressions of the killed rats were measured. Nuclear factor kappa B (NF-κB) and HO-1 expression were evaluated by immunohistochemical examination of the colonic tissue.

Result

TNBS-induced colitis significantly increased the colonic MDA levels, caspase-3 activities, and HO-1 expression in comparison to the control group. Glutamine treatment was associated with increased HO-1 expression and GSH levels and decreased MDA levels and caspase-3 activity. Histopathological examination revealed that the intestinal mucosal structure was preserved in the glutamine-treated group. In addition to this, treatment with glutamine significantly increased HO-1 expression and decreased NF-κB expression by immunohistochemistry when compared to the TNBS-induced colitis group.

Conclusion

Glutamine reduced colonic damage in TNBS-induced colitis. The mechanism of the protection associated with glutamine was due to antioxidant, antiapoptotic, anti-inflammatory, and HO-1 induction effects.

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References

  1. Cho C (2001) Current roles of nitric oxide in gastrointestinal disorders. J Physiol 95:253–256

    CAS  Google Scholar 

  2. Kankuri E, Hamalainen M, Hukkanen M, Salmenpera P, Kivilaakso E, Vapaatalo H, McCauley R, Kong SE, Heel K, Hall JC (1999) The role of glutaminase in the small intestine. Int J Biochem Cell Biol 31:405–413

    Article  Google Scholar 

  3. Stokkers P, Hommes D (2004) New cytokine therapeutics for inflammatory bowel disease. Cytokine 28:167–173

    Article  PubMed  CAS  Google Scholar 

  4. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–1046

    Article  PubMed  CAS  Google Scholar 

  5. Otterbein LE, Bach FH, Alan J, Soares M, Tao H, Wysk M, Davis RJ, Flavell RA, Choi AM (2000) Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 6:422–428

    Article  PubMed  CAS  Google Scholar 

  6. Deshane J, Wright M, Agarwal A (2005) Heme oxygenase-1 expression in disease states. Acta Biochim Pol 52:273–284

    PubMed  CAS  Google Scholar 

  7. Galbraith R (2001) Heme oxygenase: who needs it? Proc Soc Exp Biol Med 222:299–305

    Article  Google Scholar 

  8. Jobin C, Sartor RB (2000) The I kappa B/NF-kappa B system: a key determinant of mucosal inflammation and protection. Am J Physiol Cell Physiol 278:451–462

    Google Scholar 

  9. Jobin C, Sartor RB (2000) NF-kappaB signaling proteins as therapeutic targets for inflammatory bowel diseases. Inflamm Bowel Dis 6:206–213

    Article  PubMed  CAS  Google Scholar 

  10. Jian YT, Mai GF, Wang JD, Zhang YL, Luo RC, Fang YX (2005) Preventive and therapeutic effects of NF-kappaB inhibitor curcumin in rats colitis induced by trinitrobenzene sulfonic acid. World J Gastroenterol 11:1747–1752

    PubMed  CAS  Google Scholar 

  11. Potten CS, Wilson JW, Booth C (1997) Regulation and significance of apoptosis in the stem cells of the gastrointestinal epithelium. Stem Cells 15:82–93

    Article  PubMed  CAS  Google Scholar 

  12. Akdis CA, Blaser K, Akdis M (2004) Apoptosis in tissue inflammation and allergic disease. Curr Opin Immunol 16:717–723

    Article  PubMed  CAS  Google Scholar 

  13. Jones BA, Gores GJ (1997) Physiology and pathophysiology of apoptosis in epithelial cells of the liver, pancreas, and intestine. Am J Physiol 273:1174–1188

    Google Scholar 

  14. Sun F, Hamagawa E, Tsutsui C, Sakaguchi N, Kakuta Y, Tokumaru S, Kojo S (2003) Evaluation of oxidative stress during apoptosis and necrosis caused by D-galactosamine in rat liver. Biochem Pharmacol 65:101–107

    Article  PubMed  CAS  Google Scholar 

  15. Boelens PG, Nijveldt RJ, Houdijk AP, Meijer S, van Leeuwen PA (2001) Glutamine alimentation in catabolic state. J Nutr 131:69–77

    Google Scholar 

  16. Reeds PJ, Burrin DG (2001) Glutamine and the bowel. J Nutr 131:2505–2508

    Google Scholar 

  17. Al Moutaery A (2005) Proglumide attenuates experimental colitis in rats. Exp Toxicol Pathol 56:327–332

    Article  PubMed  CAS  Google Scholar 

  18. Giris M, Erbil Y, Oztezcan S, Olgac V, Barbaros U, Deveci Ui, Kirgiz B, Uysal M, Toker GA (2006) The effect of heme oxygenase-1 induction by glutamine on radiation-induced intestinal damage: the effect of heme oxygenase-1 on radiation enteritis. Am J Surg 191:503–509

    Article  PubMed  CAS  Google Scholar 

  19. Neurath M, Fuss I, Strober W (2000) TNBS-colitis. Int Rev Immunol 19:51–62

    PubMed  CAS  Google Scholar 

  20. Kim HS, Berstad A (1992) Experimental colitis in animal models. Scand J Gastroenterol 27:529–537

    PubMed  CAS  Google Scholar 

  21. Millar AD, Rampton DS, Chander CL, Claxson AW, Blades S, Coumbe A, Panetta J, Morris CJ, Blake DR (1996) Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis. Gut 39:407–415

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  23. Wei CL, Lee KH, Khoo HE, Hon WM (2003) Expression of heme oxygenase in cirrhotic rat liver. J Pathol 199:324–334

    Article  PubMed  CAS  Google Scholar 

  24. Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    Article  PubMed  CAS  Google Scholar 

  25. Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissues with Ellman’s reagent. Anal Biochem 25:192–205

    Article  PubMed  CAS  Google Scholar 

  26. Chang WK, Yang KD, Chuang H, Jan JT, Shaio MF (2002) Glutamine protects activated human T cells from apoptosis by up-regulating glutathione and Bcl-2 levels. Clin Immunol 104:151–160

    Article  PubMed  CAS  Google Scholar 

  27. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage. Nature 227:680–685

    Article  PubMed  CAS  Google Scholar 

  28. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76–85

    Article  PubMed  CAS  Google Scholar 

  29. Shusterman T, Sela S, Cohen H, Kristal B, Sbeit W, Reshef R (2003) Effect of the antioxidant Mesna (2-mercaptoethane sulfonate) on experimental colitis. Dig Dis Sci 48:1177–1185

    Article  PubMed  CAS  Google Scholar 

  30. Ademoğlu E, Erbil Y, Tam B, Barbaros U, Ilhan E, Olgaç V, Türkoğlu UM (2004) Do vitamin E and selenium have beneficial effects on Trinitrobenzenesulfonic acid-induced experimental colitis. Dig Dis Sci 49:102–108

    Article  PubMed  Google Scholar 

  31. Danese S, Sans M, Fiocchi C (2004) Inflammatory bowel disease: the role of environmental factors. Autoimmun Rev 3:394–400

    Article  PubMed  CAS  Google Scholar 

  32. Woodruff TM, Arumugam TV, Shiels IA, Newman ML, Ross PA, Reid RC, Fairlie DP, Taylor SM (2005) A potent and selective inhibitor of group II a secretory phospholipase A2 protects rats from TNBS-induced colitis. Int Immunopharmacol 5:883–892

    Article  PubMed  CAS  Google Scholar 

  33. Otterbein LE, Soares MP, Yamashita K, Bach FH (2003) Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol 24:449–455

    Article  PubMed  CAS  Google Scholar 

  34. Katori M, Anselmo DM, Busuttil RW, Kupiec-Weglinski JW (2002) A novel strategy against ischemia and reperfusion injury: cytoprotection with heme oxygenase system. Transpl Immunol 9:227–233

    Article  PubMed  CAS  Google Scholar 

  35. Wang WP, Guo X, Koo MW, Wong BC, Lam SK, Ye YN, Cho CH (2001) Protective role of heme oxygenase-1 on trinitrobenzene sulfonic acid-induced colitis in rats. Am J Physiol Gasterointest Liver Physiol 281:586–594

    Google Scholar 

  36. Attuwaybi BO, Hassoun HT, Zou L, Kozar RA, Kone BC, Weisbrodt NW, Moore FA (2003) Hypothermia protects against gut ischemia/reperfusion-induced impaired intestinal transit by inducing heme oxygenase-1. J Surg Res 115:48–55

    Article  PubMed  CAS  Google Scholar 

  37. Uehara K, Takahashi T, Fujii H, Shimizu H, Omori E, Matsumi M, Yokoyama M, Morita K, Akagi R, Sassa S (2005) The lower intestinal tract-specific induction of heme oxygenase-1 by glutamine protects against endotoxemic intestinal injury. Crit Care Med 33:381–390

    Article  PubMed  CAS  Google Scholar 

  38. Curi R, Lagranha CJ, Doi SQ, Sellitti DF, Procopio J, Pithon-Curi TC, Corless M, Newsholme P (2005) Molecular mechanisms of glutamine action. J Cell Physiol 204:392–401

    Article  PubMed  CAS  Google Scholar 

  39. Kaya E, Gur ES, Ozguc H, Bayer A, Tokyay R (1999) L-glutamine enemas attenuate mucosal injury in experimental colitis. Dis Colon Rectum 42:1209–1215

    Article  PubMed  CAS  Google Scholar 

  40. Israeli E, Berenshtein E, Wengrower D, Aptekar L, Kohen R, Zajicek G, Goldin E (2004) Prophylactic administration of topical glutamine enhances the capability of the rat colon to resist inflammatory damage. Dig Dis Sci 49:1705–1712

    Article  PubMed  CAS  Google Scholar 

  41. Buhr HJ, Kroesen AJ (1998) Ulcerative colitis, duration of conservative therapy and surgical sequelae. Langenbecks Arch Chir Suppl Kongressbd 115:148–152

    PubMed  CAS  Google Scholar 

  42. Ameho CK, Adjei AA, Harrison EK, Takeshita K, Morioka T, Arakaki Y, Ito E, Suzuki I, Kulkarni AD, Kawajiri A, Yamamoto S (1997) Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor alpha production in trinitrobenzene sulphonic acid induced colitis. Gut 41:487–493

    Article  PubMed  CAS  Google Scholar 

  43. Heuschen UA, Allemeyer EH, Hinz U, Langer K, Heuschen G, Decker-Baumann C, Herfarth C, Stern J (2002) Glutamine distribution in patients with ulcerative colitis and in patients with familial adenomatous polyposis coli before and after restorative proctocolectomy. Int J Colorectal Dis 17:245–252

    Article  PubMed  CAS  Google Scholar 

  44. Ockenga J, Borchert K, Stuber E, Lochs H, Manns MP, Bischoff SC (2005) Glutamine-enriched total parenteral nutrition in patients with inflammatory bowel disease. Eur J Clin Nutr 59:1302–1309

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Capa, Istanbul, Turkey

    Murat Giriş, Semra Doğru-Abbasoğlu & Gülçin Aykaç Toker

  2. Department of General Surgery, Istanbul Medical Faculty, Istanbul University, 34340, Capa, Istanbul, Turkey

    Yeşim Erbil, Burcu Tulumoğlu Yanık & Halil Alış

  3. Oncologic Pathology, Istanbul Medical Faculty, Istanbul University, Capa, Istanbul, Turkey

    Vakur Olgaç

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  1. Murat Giriş
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  2. Yeşim Erbil
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Correspondence to Yeşim Erbil.

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Giriş, M., Erbil, Y., Doğru-Abbasoğlu, S. et al. The effect of heme oxygenase-1 induction by glutamine on TNBS-induced colitis. Int J Colorectal Dis 22, 591–599 (2007). https://doi.org/10.1007/s00384-006-0238-y

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