Skip to main content
SpringerLink
Log in

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

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  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 38:716–722

    Article  PubMed  CAS  Google Scholar 

  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 109:149–154

    Article  PubMed  CAS  Google Scholar 

  3. Bismar MM, Sinicrope FA (2002) Radiation enteritis. Curr Gastroenterol Rep 4:361–365

    Article  PubMed  Google Scholar 

  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–S2095

    Google Scholar 

  5. Marks G, Mohiudden M (1983) The surgical management of the radiation-injured intestine. Surg Clin North Am 63:81–96

    PubMed  CAS  Google Scholar 

  6. Guzman-Stein G, Bonsack M, Liberty J, Delaney JP (1989) Abdominal radiation causes bacterial translocation. J Surg Res 46:104–107

    Article  PubMed  CAS  Google Scholar 

  7. Andreyev HJ (2007) Gastrointestinal problems after pelvic radiotherapy: the past, the present and the future. Clin Oncol 19:790–799

    Article  CAS  Google Scholar 

  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 324:911–920

    Article  PubMed  CAS  Google Scholar 

  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 89:121–125

    Article  PubMed  CAS  Google Scholar 

  10. Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–434

    Article  PubMed  CAS  Google Scholar 

  11. Barbul A, Lazarou SA, Efron DT, Wasserkrug HL, Efron G (1990) Arginine enhances wound healing and lymphocyte immune responses in humans. Surgery 108:331–336

    PubMed  CAS  Google Scholar 

  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 74:149–154

    Article  PubMed  CAS  Google Scholar 

  13. Morris SM (2004) Enzymes of arginine metabolism. J Nutr 134(10 Suppl):2743S–2747S

    PubMed  CAS  Google Scholar 

  14. Hall JC (1998) Glycine. J Parenter Enteral Nutr 22:393–398

    Article  CAS  Google Scholar 

  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 6:229–240

    Article  PubMed  CAS  Google Scholar 

  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 31:391–398

    Article  Google Scholar 

  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 69:5883–5891

    Article  PubMed  CAS  Google Scholar 

  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 134:457–466

    Article  PubMed  Google Scholar 

  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 40:197–204

    Article  PubMed  CAS  Google Scholar 

  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–G103

    PubMed  CAS  Google Scholar 

  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 164:176–182

    PubMed  CAS  Google Scholar 

  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 22:1523–1529

    Article  PubMed  Google Scholar 

  23. Marques RG, Morales MM, Petroianu A (2009) Brazilian law for scientific use of animals. Acta Cir Bras 24:69–74

    Article  PubMed  Google Scholar 

  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 96:379–394

    CAS  Google Scholar 

  25. Mandarim-de-Lacerda CA (2003) Stereological tools in biomedical research. An Acad Bras Cienc 75:469–486

    PubMed  Google Scholar 

  26. Breiter N, Trott KR (1986) The pathogenesis of the chronic radiation ulcer of the large bowel in rats. Br J Cancer Suppl 7:29–30

    PubMed  CAS  Google Scholar 

  27. Nielsen OH, Vainer B, Rask-Madsen J (2008) Non-IBD and noninfectious colitis. Nat Clin Pract Gastroenterol Hepatol 5:28–39

    Article  PubMed  Google Scholar 

  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 171:180–187

    Article  PubMed  CAS  Google Scholar 

  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 23:561–569

    Article  PubMed  CAS  Google Scholar 

  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 88:689–695

    Article  PubMed  CAS  Google Scholar 

  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 125:1040–1045

    PubMed  CAS  Google Scholar 

  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 48:1–5

    Article  PubMed  CAS  Google Scholar 

  33. Tsune I, Ikejima K, Hirose M, Yoshikawa M (2003) Dietary glycine prevents chemical-induced experimental colitis in rat. Gastroenterology 125:775–785

    Article  PubMed  CAS  Google Scholar 

  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, Doc24

    Google Scholar 

  35. Lee MA, McCauley RD, Kong SE, Hall JC (2002) Influence of glycine on intestinal ischemia–reperfusion injury. J Parenter Enteral Nutr 26:130–135

    Article  CAS  Google Scholar 

  36. Picard C, Wysocki J, Fioramonti J, Griffiths NM (2001) Intestinal and colonic motor alterations associated with irradiation-induced diarrhoea in rats. Neurogastroenterol Motil 13:19–26

    Article  PubMed  CAS  Google Scholar 

  37. Huang EY, Wang CJ, Hsu HC, Sun LM (2006) Characteristics and predictive factors of early-onset diarrhoea during pelvic irradiation. Br J Radiol 79:419–424

    Article  PubMed  CAS  Google Scholar 

  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 184:526–530

    Google Scholar 

  39. Fajardo LF (2005) The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncol 44:13–22

    Article  PubMed  Google Scholar 

  40. Salzman AL (1995) Nitric oxide in the gut. New Horiz 3:352–364

    PubMed  CAS  Google Scholar 

  41. Suchner U, Heyland DK, Peter K (2002) Immune-modulatory actions of arginine in the critically ill. Br J Nutr 87(Suppl 1):S121–S132

    Article  PubMed  CAS  Google Scholar 

  42. Liu XM, Chapman GB, Peyton KJ, Schafer AI, Durante W (2002) Carbon monoxide inhibits apoptosis in vascular smooth muscle cells. Cardiovasc Res 55:396–405

    Article  PubMed  CAS  Google Scholar 

  43. Grémy O, Benderitter M, Linard C (2008) Acute and persisting Th2-like immune response after fractionated colorectal γ-irradiation. World J Gastroenteol 14:7075–7085

    Article  Google Scholar 

  44. Durante W, Johnson FK, Johnson RA (2007) Arginase: a critical regulator of nitric oxide synthesis and vascular function. Clin Exp Pharmacol Physiol 34:906–911

    Article  PubMed  CAS  Google Scholar 

  45. Albina JE, Abate JA, Mastrofrancesco B (1993) Role of ornithine as a praline precursor in healing wounds. J Surg Res 55:97–102

    Article  PubMed  CAS  Google Scholar 

  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 49:55–62

    Article  PubMed  Google Scholar 

  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 102:431–442

    PubMed  CAS  Google Scholar 

  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 297:35–42

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Experimental Surgery, Rio de Janeiro State University, Rio de Janeiro, Brazil

    Etiene de Aguiar Picanço, Carlos Eduardo R. Caetano, Mônica Vieira Mano de Souza & Gabriela Mendes Moscoso

  2. Department of General Surgery, Rio de Janeiro State University, Rua Clóvis Salgado 255/204, Recreio, Rio de Janeiro, RJ, 22795-230, Brazil

    Francisco Lopes-Paulo & Ruy G. Marques

  3. Nutrition Division, Pedro Ernesto University Hospital, Rio de Janeiro State University, Rio de Janeiro, Brazil

    Cristina F. Diestel

  4. Department of Urogenital Anatomy, Rio de Janeiro State University, Rio de Janeiro, Brazil

    Helena Maria F. Pazos

Authors
  1. Etiene de Aguiar Picanço
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francisco Lopes-Paulo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruy G. Marques
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cristina F. Diestel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carlos Eduardo R. Caetano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mônica Vieira Mano de Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gabriela Mendes Moscoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Helena Maria F. Pazos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ruy G. Marques.

Additional information

This work was partially supported by a grant from Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Brazil.

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Aguiar Picanço, E., Lopes-Paulo, F., Marques, R.G. et al. L-arginine and glycine supplementation in the repair of the irradiated colonic wall of rats. Int J Colorectal Dis 26, 561–568 (2011). https://doi.org/10.1007/s00384-011-1154-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-011-1154-3

Keywords

Search

Navigation