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

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Abstract

Background

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

Aim

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

Methods

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.

Results

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).

Conclusions

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.

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References

  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.

    PubMed  CAS  Google Scholar 

  2. Soergel KH. Colonic fermentation: metabolic and clinical implications. Clin Invest. 1994;72:742–748.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  4. Roediger WE, Millard S. Selective inhibition of fatty acid oxidation in colonocytes by ibuprofen: a cause of colitis? Gut. 1995;36:55–59.

    Article  PubMed  CAS  Google Scholar 

  5. Glotzer DJ, Glick ME, Goldman H. Proctitis and colitis following diversion of faecal stream. Gastroenterology. 1981;80:438–441.

    PubMed  CAS  Google Scholar 

  6. Roediger WE. The starved colon—diminished mucosal nutrition, diminished absorption, and colitis. Dis Colon Rectum. 1990;33:858–862.

    Article  PubMed  CAS  Google Scholar 

  7. Villanacci V, Talbot IC, Rossi E, Bassotti G. Ischaemia: a pathogenetic clue in diversion colitis? Colorectal Dis. 2007;9:601–605.

    Article  PubMed  CAS  Google Scholar 

  8. Neut C, Guillemot F, Colombel JF. Nitrate-reducing bacteria in diversion colitis: a clue to inflammation? Dig Dis Sci. 1997;42:2577–2580.

    Article  PubMed  CAS  Google Scholar 

  9. Neut C, Colombel JF, Guillemot F, et al. Impaired bacterial flora in human excluded colon. Gut. 1989;30:1094–1098.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  11. Agarwal VP, Schimmel EM. Diversion colitis: a nutritional deficiency syndrome? Nutr Rev. 1989;47:257–261.

    Article  PubMed  CAS  Google Scholar 

  12. Scheppach W, Weiler F. The butyrate story: old wine in new bottles? Curr Opin Clin Nutr Metab Care. 2004;7:563–567.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  15. Ferguson CM, Siegel RJ. A prospective evaluation of diversion colitis. Am Surg. 1991;57:46–49.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  17. Edwards CM, George B, Warren B. Diversion colitis—new light through old windows. Histopathology. 1999;34:1–5.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  23. Pravda J. Radical induction theory of ulcerative colitis. World J Gastroenterol. 2005;11:2371–2384.

    PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  37. Truelove SC, Richards WCD. Biopsy studies in ulcerative colitis. Br Med J. 1956;1:1315–1322.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  39. Sheenan J, Brynjolfsson G. Ulcerative colitis following hydrogen peroxide enema. Lab Invest. 1960;9:150–167.

    Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

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

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Correspondence to Carlos Augusto Real Martinez.

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Martinez, C.A.R., de Almeida, M.G., da Silva, C.M.G. et al. Enemas with n-Acetylcysteine Can Reduce the Level of Oxidative Damage in Cells of the Colonic Mucosa Diverted from the Faecal Stream. Dig Dis Sci 58, 3452–3459 (2013). https://doi.org/10.1007/s10620-013-2768-9

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  • DOI: https://doi.org/10.1007/s10620-013-2768-9

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