Digestive Diseases and Sciences

, Volume 58, Issue 12, pp 3452–3459 | Cite as

Enemas with n-Acetylcysteine Can Reduce the Level of Oxidative Damage in Cells of the Colonic Mucosa Diverted from the Faecal Stream

  • Carlos Augusto Real MartinezEmail author
  • Marcos Gonçalves de Almeida
  • Camila Moraes Gonçalves da Silva
  • Marcelo Lima Ribeiro
  • Fernando Lorenzetti da Cunha
  • Murilo Rocha Rodrigues
  • Daniela Tiemi Sato
  • José Aires Pereira
Original Article



Oxidative stress has been related to inflammation of the colonic mucosa in patients with diversion colitis (DC).


The purpose of this study was to evaluate the antioxidants effects of n-acetylcysteine (NAC) in colon segments without faecal stream.


Thirty-six Wistar rats were subjected to diversion of the faecal stream by proximal colostomy and a distal mucosal colon fistula. They were distributed into three experimental groups of 12 animals each; the animals in each group underwent daily enemas containing saline solution (control group) or either a 25 or 100 mg/kg dose of NAC (treated groups). In each group, animals were sacrificed after 2 or 4 weeks. The degree of inflammation was determined by histopathological analysis and stratified by inflammatory grading scale. Oxidative DNA damage was measured by comet assay. The Mann–Whitney test and ANOVA were used for statistical analysis; p < 0.05 was considered significant.


The oxidative DNA damage in colon segments without faecal stream was significantly lower in animals treated with either concentration of NAC than in control group, regardless of the duration of intervention (p < 0.01).


Intrarectal application of NAC reduces the inflammation as well as DNA oxidative damage and could be beneficial as a complementary agent in the treatment of DC.


n-Acetylcysteine Colitis Reactive oxygen species Oxidative stress Comet assay Short-chain fatty acids 



Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP). Process Number: 2010/12492-7.

Conflict of interest



  1. 1.
    Haas PA, Fox TA Jr, Szilagy EJ. Endoscopic examination of the colon and rectum distal to a colostomy. Am J Gastroenterol. 1990;85:850–854.PubMedGoogle Scholar
  2. 2.
    Soergel KH. Colonic fermentation: metabolic and clinical implications. Clin Invest. 1994;72:742–748.CrossRefGoogle Scholar
  3. 3.
    Mortensen PB, Clausen MR. Short chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scand J Gastroenterol Suppl. 1996;216:132–148.PubMedCrossRefGoogle Scholar
  4. 4.
    Roediger WE, Millard S. Selective inhibition of fatty acid oxidation in colonocytes by ibuprofen: a cause of colitis? Gut. 1995;36:55–59.PubMedCrossRefGoogle Scholar
  5. 5.
    Glotzer DJ, Glick ME, Goldman H. Proctitis and colitis following diversion of faecal stream. Gastroenterology. 1981;80:438–441.PubMedGoogle Scholar
  6. 6.
    Roediger WE. The starved colon—diminished mucosal nutrition, diminished absorption, and colitis. Dis Colon Rectum. 1990;33:858–862.PubMedCrossRefGoogle Scholar
  7. 7.
    Villanacci V, Talbot IC, Rossi E, Bassotti G. Ischaemia: a pathogenetic clue in diversion colitis? Colorectal Dis. 2007;9:601–605.PubMedCrossRefGoogle Scholar
  8. 8.
    Neut C, Guillemot F, Colombel JF. Nitrate-reducing bacteria in diversion colitis: a clue to inflammation? Dig Dis Sci. 1997;42:2577–2580.PubMedCrossRefGoogle Scholar
  9. 9.
    Neut C, Colombel JF, Guillemot F, et al. Impaired bacterial flora in human excluded colon. Gut. 1989;30:1094–1098.PubMedCrossRefGoogle Scholar
  10. 10.
    Harig JM, Soergel KH, Komorowski RA, Wood CM. Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med. 1989;320:23–28.PubMedCrossRefGoogle Scholar
  11. 11.
    Agarwal VP, Schimmel EM. Diversion colitis: a nutritional deficiency syndrome? Nutr Rev. 1989;47:257–261.PubMedCrossRefGoogle Scholar
  12. 12.
    Scheppach W, Weiler F. The butyrate story: old wine in new bottles? Curr Opin Clin Nutr Metab Care. 2004;7:563–567.PubMedCrossRefGoogle Scholar
  13. 13.
    Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ. Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol. 2006;40:235–243.PubMedCrossRefGoogle Scholar
  14. 14.
    Szczepkowski M, Kobus A, Borycka K. How to treat diversion colitis? Current state of medical knowledge, own research and experience. Acta Chir Iugosl. 2008;55:77–81.PubMedCrossRefGoogle Scholar
  15. 15.
    Ferguson CM, Siegel RJ. A prospective evaluation of diversion colitis. Am Surg. 1991;57:46–49.PubMedGoogle Scholar
  16. 16.
    Scheppach W, Christl SU, Bartram HP, Richter F, Kasper H. Effects of short-chain fatty acids on the inflamed colonic mucosa. Scand J Gastroenterol Suppl. 1997;222:53–57.PubMedGoogle Scholar
  17. 17.
    Edwards CM, George B, Warren B. Diversion colitis—new light through old windows. Histopathology. 1999;34:1–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Kiely EM, Ajayi NA, Wheeler RA, Malone M. Diversion procto-colitis: response to treatment with short-chain fatty acids. J Pediatr Surg. 2001;36:1514–1517.PubMedCrossRefGoogle Scholar
  19. 19.
    de Oliveira-Neto JP, de Aguilar-Nascimento JE. Intraluminal irrigation with fibers improves mucosal inflammation and atrophy in diversion colitis. Nutrition. 2004;20:197–199.PubMedCrossRefGoogle Scholar
  20. 20.
    Oliveira AJ, Pinto Júnior FE, Formiga MC, Melo SP, Brandao-Neto J, Ramos AM. Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats. Clinics (Sao Paulo). 2010;65:1351–1356.CrossRefGoogle Scholar
  21. 21.
    Lameiro TMM, Silva CMG, Marques LHS, et al. Effects of butyrate on levels of lipid peroxidation in cells of the colonic mucosa without fecal stream: experimental study in rats. Rev Bras Coloproctol. 2011;31:155–164.CrossRefGoogle Scholar
  22. 22.
    Martinez CAR, Ribeiro ML, Gambero A, Miranda DDC, Pereira JA, Nadal SR. The importance of oxygen free radicals in the etiopathogenesis of diversion colitis in rats. Acta Cir Bras. 2010;25:387–395.PubMedCrossRefGoogle Scholar
  23. 23.
    Pravda J. Radical induction theory of ulcerative colitis. World J Gastroenterol. 2005;11:2371–2384.PubMedGoogle Scholar
  24. 24.
    Marques LHS, Silva CMG, Lameiro TMM, et al. Evaluation of lipid peroxidation levels on mucosa colonic cells after application of hydrogen peroxide in enemas: experimental study in rats. Rev Bras Coloproct. 2010;30:272–280.CrossRefGoogle Scholar
  25. 25.
    Longatti TS, Acedo SC, de Oliveira CC, et al. Inflammatory alterations in excluded colon in rats: a comparison with chemically induced colitis. Scand J Gastroenterol. 2010;45:315–324.PubMedCrossRefGoogle Scholar
  26. 26.
    Sousa MV, Priolli DG, Portes AV, Cardinalli IA, Pereira JA, Martinez CA. Evaluation by computerized morphometry of histopathological alterations of the colon wall in segments with and without intestinal transit in rats. Acta Cir Bras. 2008;23:417–424.PubMedCrossRefGoogle Scholar
  27. 27.
    Nonose R, Spadari APP, Priolli DG, Máximo FR, Pereira JA, Martinez CAR. Tissue quantification of neutral and acid mucins in the mucosa of the colon with and without fecal stream in rats. Acta Cir Bras. 2009;24:267–275.PubMedCrossRefGoogle Scholar
  28. 28.
    Martinez CA, Nonose R, Spadari AP, et al. Quantification by computerized morphometry of tissue levels of sulfomucins and sialomucins in diversion colitis in rats. Acta Cir Bras. 2010;25:231–240.PubMedCrossRefGoogle Scholar
  29. 29.
    Caltabiano C, Máximo FR, Spadari AP, et al. 5-aminosalicylic acid (5-ASA) can reduce levels of oxidative DNA damage in cells of colonic mucosa with and without fecal stream. Dig Dis Sci. 2011;56:1037–1046.PubMedCrossRefGoogle Scholar
  30. 30.
    Seril DN, Liao J, Ho KLK, Yang SC, Yang GY. Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animals models. Carcinogenesis. 2003;24:353–362.PubMedCrossRefGoogle Scholar
  31. 31.
    Ribeiro ML, Priolli DG, Miranda DDC, Arçari DP, Pedrazzoli J Jr, Martinez CAR. Analysis of oxidative DNA damage in patients with colorectal cancer. Clin Colorectal Cancer. 2008;7:267–272.PubMedCrossRefGoogle Scholar
  32. 32.
    Poulsen HE, Prieme H, Loft S. Role of oxidative DNA damage in cancer initiation and promotion. Eur J Cancer Prev. 1998;7:9–16.PubMedGoogle Scholar
  33. 33.
    Seril D, Liao J, Ho KK, Yang CY, Yang GY. Inhibition of chronic ulcerative colitis-associates colorectal adenocarcinoma development in a murine model by N-acetylcysteine. Carcinogenesis. 2002;23:993–1001.PubMedCrossRefGoogle Scholar
  34. 34.
    Akgun E, Çaliskan C, Celik HA, Ozutemiz AO, Tuncyurek M, Aydin HH. Effects of N-acetylcysteine treatment on oxidative stress in acetic acid-induced experimental colitis in rats. J Int Med Res. 2005;33:196–206.PubMedCrossRefGoogle Scholar
  35. 35.
    Cetinkaya A, Bulbuloglu E, Kurutas EB, Ciralik H, Kantarceken B, Buyukbese MA. Beneficial effects of N-acetylcysteine on acetic acid-induced colitis in rats. Tohoku J Exp Med. 2005;206:131–139.PubMedCrossRefGoogle Scholar
  36. 36.
    Millar AD, Rampton DS, Chander CL, et al. Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis. Gut. 1996;39:407–415.PubMedCrossRefGoogle Scholar
  37. 37.
    Truelove SC, Richards WCD. Biopsy studies in ulcerative colitis. Br Med J. 1956;1:1315–1322.PubMedCrossRefGoogle Scholar
  38. 38.
    Ahmad T, Satsangi J, McGovern D, Bunce M, Jewell DP. Review article: the genetics of inflammatory bowel disease. Aliment Pharmacol Ther. 2001;15:731–748.PubMedCrossRefGoogle Scholar
  39. 39.
    Sheenan J, Brynjolfsson G. Ulcerative colitis following hydrogen peroxide enema. Lab Invest. 1960;9:150–167.Google Scholar
  40. 40.
    Cunha FL, Silva CMG, Almeida MG, et al. Reduction in oxidative stress levels in the colonic mucosa without fecal stream after the application of enemas containing aqueous Ilex paraguariensis extract. Acta Cir Bras. 2011;26:289–296.PubMedCrossRefGoogle Scholar
  41. 41.
    Rutgeerts P, Van Deventer S, Schreiber S. Review article: the expanding role of biological agents in the treatment of inflammatory bowel disease—focus on selective adhesion molecule inhibition. Aliment Pharmacol Ther. 2003;17:1435–1450.PubMedCrossRefGoogle Scholar
  42. 42.
    Nosál’ová V, Cerná S, Bauer V. Effect of N-acetylcysteine on colitis induced by acetic acid in rats. Gen Pharmacol. 2000;35:77–81.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Carlos Augusto Real Martinez
    • 1
    Email author
  • Marcos Gonçalves de Almeida
    • 2
  • Camila Moraes Gonçalves da Silva
    • 3
  • Marcelo Lima Ribeiro
    • 2
  • Fernando Lorenzetti da Cunha
    • 2
  • Murilo Rocha Rodrigues
    • 2
  • Daniela Tiemi Sato
    • 2
  • José Aires Pereira
    • 2
  1. 1.Post-Graduate Program in Health ScienceSão Francisco UniversitySanto AndréBrazil
  2. 2.Post-Graduate Program in Health Science, São Francisco University Medical SchoolBragança PaulistaBrazil
  3. 3.State University of CampinasCampinasBrazil

Personalised recommendations