L-arginine and glycine supplementation in the repair of the irradiated colonic wall of rats

  • Etiene de Aguiar Picanço
  • Francisco Lopes-Paulo
  • Ruy G. Marques
  • Cristina F. Diestel
  • Carlos Eduardo R. Caetano
  • Mônica Vieira Mano de Souza
  • Gabriela Mendes Moscoso
  • Helena Maria F. Pazos
Original Article



Radiotherapy is widely used for cancer treatment but has harmful effects. This study aimed to assess the effects of L-arginine and glycine supplementation on the colon wall of rats submitted to abdominal irradiation.


Forty male Wistar rats were randomly divided into four groups: I—healthy, II—irradiated with no amino acid supplementation, III—irradiated and supplemented with L-arginine, and IV—irradiated and supplemented with glycine. The animals received supplementation for 14 days, with irradiation being applied on the eighth day of the experiment. All animals underwent laparotomy on the 15th day for resection of a colonic segment for stereologic analysis. Parametric and nonparametric tests were used for statistical analysis, with the level of significance set at p ≤0.05.


Stereologic analysis showed that irradiation induced a reduction of the total volume of the colon wall of group II and III animals compared to healthy controls, but not of group IV animals supplemented with glycine. The mucosal layer of the irradiated animals of all groups was reduced compared to healthy group I animals, but supplementation with L-arginine and glycine was effective in maintaining the epithelial surface of the mucosal layer.


The present results suggest that glycine supplementation had a superior effect on the irradiated colon wall compared to L-arginine supplementation since it was able to maintain the thickness of the wall and the epithelial surface of the mucosa, whereas L-arginine maintained the partial volume of the epithelium and the epithelial surface, but not the total volume of the intestinal wall.


L-arginine Glycine Irradiation Colitis Nutrition Radiotherapy 


  1. 1.
    Carroll MP, Zera RT, Roberts JC, Schlafmann SE, Feeney DA, Johnston GR et al (1995) Efficacy of radioprotective agents in preventing small and large bowel radiation injury. Dis Colon Rectum 38:716–722PubMedCrossRefGoogle Scholar
  2. 2.
    Hwang JM, Chan DC, Chang TM, Tsao TY, Tsou SS, Lu RH, Tsai LM (2003) Effects of oral arginine and glutamine on radiation-induced injury in the rat. J Surg Res 109:149–154PubMedCrossRefGoogle Scholar
  3. 3.
    Bismar MM, Sinicrope FA (2002) Radiation enteritis. Curr Gastroenterol Rep 4:361–365PubMedCrossRefGoogle Scholar
  4. 4.
    Diestel CF, Lopes-Paulo F, Marques RG, Horst NL, Caetano CE (2005) Effect of oral supplement of L-glutamine in colonic wall of rats subjected to abdominal irradiation. Acta Cir Bras 20(1):S2005–S2095Google Scholar
  5. 5.
    Marks G, Mohiudden M (1983) The surgical management of the radiation-injured intestine. Surg Clin North Am 63:81–96PubMedGoogle Scholar
  6. 6.
    Guzman-Stein G, Bonsack M, Liberty J, Delaney JP (1989) Abdominal radiation causes bacterial translocation. J Surg Res 46:104–107PubMedCrossRefGoogle Scholar
  7. 7.
    Andreyev HJ (2007) Gastrointestinal problems after pelvic radiotherapy: the past, the present and the future. Clin Oncol 19:790–799CrossRefGoogle Scholar
  8. 8.
    Linard C, Grémy O, Benderitter M (2008) Reduction of peroxisome proliferation activated receptor gamma expression by gamma-irradiation as a mechanism contributing to inflammatory response in rat colon: modulation by the 5-aminosalicylic acid agonist. J Pharmacol Exp Ther 324:911–920PubMedCrossRefGoogle Scholar
  9. 9.
    Ersin S, Tuncyurek P, Esassolak M, Alkanat M, Buke C, Yilmaz M et al (2000) The prophylactic and therapeutic effects of glutamine and arginine enriched diets on radiation-induced enteritis in rats. J Surg Res 89:121–125PubMedCrossRefGoogle Scholar
  10. 10.
    Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–434PubMedCrossRefGoogle Scholar
  11. 11.
    Barbul A, Lazarou SA, Efron DT, Wasserkrug HL, Efron G (1990) Arginine enhances wound healing and lymphocyte immune responses in humans. Surgery 108:331–336PubMedGoogle Scholar
  12. 12.
    Gurbuz AT, Kunzelman J, Ratze EE (1998) Supplemental dietary arginine accelerates intestinal mucosal regeneration and enhances bacterial clearance following radiation enteritis in rats. J Surg Res 74:149–154PubMedCrossRefGoogle Scholar
  13. 13.
    Morris SM (2004) Enzymes of arginine metabolism. J Nutr 134(10 Suppl):2743S–2747SPubMedGoogle Scholar
  14. 14.
    Hall JC (1998) Glycine. J Parenter Enteral Nutr 22:393–398CrossRefGoogle Scholar
  15. 15.
    Zhong Z, Wheeler MD, Li X, Froh M, Schemmer P, Yin M et al (2003) L-glycine: a novel anti-inflammatory, immunomodulatory, and cytoprotective agent. Curr Opin Clin Nutr Metab Care 6:229–240PubMedCrossRefGoogle Scholar
  16. 16.
    Limuro Y, Bradford BU, Yamashina S, Rusyn I, Nakagamy M, Enomoto N et al (2000) The glutathione precursor L-2-oxothiazolidine-4-carboxylic acid protects against liver injury due to chronic enteral ethanol exposure in the rat. Hepatology 31:391–398CrossRefGoogle Scholar
  17. 17.
    Li X, Bradford BU, Wheeler MD, Stimpson SA, Pink HM, Brodie TA et al (2001) Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel. Infect Immun 69:5883–5891PubMedCrossRefGoogle Scholar
  18. 18.
    Jacob T, Ascher E, Hingorani A, Kallakuri S (2003) Glycine prevents the induction of apoptosis attributed to mesenteric ischemia/reperfusion injury in a rat model. Surgery 134:457–466PubMedCrossRefGoogle Scholar
  19. 19.
    Yamashina S, Konno A, Wheeler MD, Rusyn I, Rusyn EV, Cox AD et al (2001) Endothelial cells contain a glycine-gated chloride channel. Nutr Cancer 40:197–204PubMedCrossRefGoogle Scholar
  20. 20.
    Ikejima K, Iimuro Y, Forman DT, Thurman RG (1996) A diet containing glycine improves survival in endotoxin shock in the rat. Am J Physiol 271:G97–G103PubMedGoogle Scholar
  21. 21.
    Stachlewitz RF, Li X, Smith S, Bunzendahl H, Graves LM, Thurman RG (2000) Glycine inhibits growth of T lymphocytes by an IL-2-independent mechanism. J Immunol 164:176–182PubMedGoogle Scholar
  22. 22.
    Diestel CF, Marques RG, Lopes-Paulo F, Paiva D, Horst NL, Caetano CE, Portela MC (2007) Role of L-glutamine and glycine supplementation on irradiated colonic wall. Int J Colorectal Dis 22:1523–1529PubMedCrossRefGoogle Scholar
  23. 23.
    Marques RG, Morales MM, Petroianu A (2009) Brazilian law for scientific use of animals. Acta Cir Bras 24:69–74PubMedCrossRefGoogle Scholar
  24. 24.
    Gundersen HJ, Bendtsen TF, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A et al (1988) Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. Acta Pathol Microbiol Immunol Scand 96:379–394Google Scholar
  25. 25.
    Mandarim-de-Lacerda CA (2003) Stereological tools in biomedical research. An Acad Bras Cienc 75:469–486PubMedGoogle Scholar
  26. 26.
    Breiter N, Trott KR (1986) The pathogenesis of the chronic radiation ulcer of the large bowel in rats. Br J Cancer Suppl 7:29–30PubMedGoogle Scholar
  27. 27.
    Nielsen OH, Vainer B, Rask-Madsen J (2008) Non-IBD and noninfectious colitis. Nat Clin Pract Gastroenterol Hepatol 5:28–39PubMedCrossRefGoogle Scholar
  28. 28.
    Shukla J, Chatterjee S, Thakur VS, Premachandran S, Checker R, Poduval TB (2009) L-arginine reverses radiation-induced immune dysfunction: the need for optimum treatment window. Radiat Res 171:180–187PubMedCrossRefGoogle Scholar
  29. 29.
    Shang HF, Wang YY, Lai YN, Chiu WC, Yeh SL (2004) Effects of arginine supplementation on mucosal immunity in rats with septic peritonitis. Clin Nutr 23:561–569PubMedCrossRefGoogle Scholar
  30. 30.
    Moinard C, Caldefie-Chezet F, Walrand S, Vasson MP, Cynober L (2002) Evidence that glutamine modulates respiratory burst in stressed rat polymorphonuclear cells through its metabolism into arginine. Br J Nutr 88:689–695PubMedCrossRefGoogle Scholar
  31. 31.
    Klimberg VS, Salloum RM, Kasper M, Plumley DA, Dolson DJ, Hautamaki RD et al (1990) Oral glutamine accelerates healing of the small intestine and improves outcome after whole abdominal radiation. Arch Surg 125:1040–1045PubMedGoogle Scholar
  32. 32.
    Souba WW, Klimberg VS, Hautamaki RD, Mendenhall WH, Bova FC, Howard RJ et al (1990) Oral glutamine reduces bacterial translocation following abdominal radiation. J Surg Res 48:1–5PubMedCrossRefGoogle Scholar
  33. 33.
    Tsune I, Ikejima K, Hirose M, Yoshikawa M (2003) Dietary glycine prevents chemical-induced experimental colitis in rat. Gastroenterology 125:775–785PubMedCrossRefGoogle Scholar
  34. 34.
    Stein J, Boehles HJ, Blumenstein I, Goeters C, Schulz R (2009) Amino acids—guidelines on parenteral nutrition, chapter 4. Ger Med Sci 18:7, Doc24Google Scholar
  35. 35.
    Lee MA, McCauley RD, Kong SE, Hall JC (2002) Influence of glycine on intestinal ischemia–reperfusion injury. J Parenter Enteral Nutr 26:130–135CrossRefGoogle Scholar
  36. 36.
    Picard C, Wysocki J, Fioramonti J, Griffiths NM (2001) Intestinal and colonic motor alterations associated with irradiation-induced diarrhoea in rats. Neurogastroenterol Motil 13:19–26PubMedCrossRefGoogle Scholar
  37. 37.
    Huang EY, Wang CJ, Hsu HC, Sun LM (2006) Characteristics and predictive factors of early-onset diarrhoea during pelvic irradiation. Br J Radiol 79:419–424PubMedCrossRefGoogle Scholar
  38. 38.
    Luccichenti G, Cademartiri F, Sianesi M, Roncoroni L, Pavone P, Krestin GP (2005) Radiologic assessment of rectosigmoid cancer before and after neoadjuvant radiation therapy: comparison between quantitation techniques. Am J Roentgenol 184:526–530Google Scholar
  39. 39.
    Fajardo LF (2005) The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncol 44:13–22PubMedCrossRefGoogle Scholar
  40. 40.
    Salzman AL (1995) Nitric oxide in the gut. New Horiz 3:352–364PubMedGoogle Scholar
  41. 41.
    Suchner U, Heyland DK, Peter K (2002) Immune-modulatory actions of arginine in the critically ill. Br J Nutr 87(Suppl 1):S121–S132PubMedCrossRefGoogle Scholar
  42. 42.
    Liu XM, Chapman GB, Peyton KJ, Schafer AI, Durante W (2002) Carbon monoxide inhibits apoptosis in vascular smooth muscle cells. Cardiovasc Res 55:396–405PubMedCrossRefGoogle Scholar
  43. 43.
    Grémy O, Benderitter M, Linard C (2008) Acute and persisting Th2-like immune response after fractionated colorectal γ-irradiation. World J Gastroenteol 14:7075–7085CrossRefGoogle Scholar
  44. 44.
    Durante W, Johnson FK, Johnson RA (2007) Arginase: a critical regulator of nitric oxide synthesis and vascular function. Clin Exp Pharmacol Physiol 34:906–911PubMedCrossRefGoogle Scholar
  45. 45.
    Albina JE, Abate JA, Mastrofrancesco B (1993) Role of ornithine as a praline precursor in healing wounds. J Surg Res 55:97–102PubMedCrossRefGoogle Scholar
  46. 46.
    Igaki H, Nakagawa K, Uozaki H, Akahane M, Hosoi Y, Fukayama M et al (2008) Pathological changes in the gastrointestinal tract of a heavily radiation-exposed worker at the Tokai-mura criticality accident. J Radiat Res 49:55–62PubMedCrossRefGoogle Scholar
  47. 47.
    Matthes H, Herbst H, Schuppan D, Stallmach A, Milani S, Stein H et al (1992) Cellular localization of procollagen gene transcripts in inflammatory bowel diseases. Gastroenterology 102:431–442PubMedGoogle Scholar
  48. 48.
    Wang J, Zheng H, Hauer-Jensen M (2001) Influence of short-term octreotide administration on chronic tissue injury, transforming growth factor beta (TGF-beta) overexpression, and collagen accumulation in irradiated rat intestine. J Pharmacol Exp Ther 297:35–42PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Etiene de Aguiar Picanço
    • 1
  • Francisco Lopes-Paulo
    • 2
  • Ruy G. Marques
    • 2
  • Cristina F. Diestel
    • 3
  • Carlos Eduardo R. Caetano
    • 1
  • Mônica Vieira Mano de Souza
    • 1
  • Gabriela Mendes Moscoso
    • 1
  • Helena Maria F. Pazos
    • 4
  1. 1.Laboratory of Experimental SurgeryRio de Janeiro State UniversityRio de JaneiroBrazil
  2. 2.Department of General SurgeryRio de Janeiro State UniversityRio de JaneiroBrazil
  3. 3.Nutrition Division, Pedro Ernesto University HospitalRio de Janeiro State UniversityRio de JaneiroBrazil
  4. 4.Department of Urogenital AnatomyRio de Janeiro State UniversityRio de JaneiroBrazil

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