Atilla TÖRÜNER, Arda DEMİRKAN, Mehmet Ayhan KUZU, Murat AKSOY

Deneysel ileusda indometasin kullanımının intestinal permeabilite ve bakteriyel translokasyon üzerine etkileri

Amaç: Çalışmamızda mekanik intestinal obstrüksiyonlarda antiinflamatuvar bir ajan olarak indometasinin, intestinal permeabilite, bakteriyel translokasyon ve histopatolojik değişiklikler üzerindeki etkilerinin ortaya konulması amaçlanmıştır. Gereç ve Yöntem: Çalışmada her biri 10 hayvandan oluşan 4 grup oluşturulmuştur. Grup I (n=10) kontrol grubunu oluştururken, grup II (n=10) de terminal ileum ipek materyal ile 24 saat süresince bağlanarak deneysel ileus oluşturuldu. Grup III deki (n=10) hayvanlara 5 mg/kg subkutan indometasin uygulaması yapıldı. Grup IV de (n=10) ise intestinal obstrüksiyonu takiben indometasin uygulaması gerçekleştirildi. Grup IV de ileus oluşturulması ve indometasin uygulamaları grup II ve grup III deki ile aynı biçimde gerçekleştirildi. 51Cr ile işaretli etilen diamin tetraasetik asite (51Cr EDTA) olan intestinal permeabilite değişiklikleri laparatomilerden 24 saat sonra ve 6 saat süresince toplanan idrar örneklerinde değerlendirildi. Bakteriyel translokasyon mezenterik lenf nodları ve kan örnekleri kültüre edilerek değerlendirildi. Deney hayvanlarından intestinal doku örnekleri de alınarak histopatolojik değişiklikler ve kuru-yaş ağırlık değişiklikleri değerlendirildi. Bulgular: Deneysel ileus oluşturulmasını takiben geçekleştirilen indometasin uygulamasının, ileusa bağlı olarak artmış olan intestinal permeabiliteyi anlamlı biçimde azaltırken (%3.5±0.10 - %2.0±0.20, p

The effects of indomethacine on intestinal permeability and bacterial translocation in intestinal obstruction

Aim: The aim of this study was to investigate the effects of indomethacine as an anti-inflammatory agent, on intestinal permeability, bacterial translocation and histopathological changes in experimental intestinal obstruction. Materials and Methods: Forthy Wistar rats were divided into four groups, a control group (group I, n=10); an intestinal obstruction group (group II, n=10) in which terminal ileum was obstructed by ligation for 24 hours, an indomethacine group (group III, n=10) treated with subcutaneous indomethacine (5 mg/kg) after the ligation; and an indomethacine + intestinal obstruction group (group IV, n=10). Intestinal obstruction period and indomethacine dosages were same as in group II and III, respectively. Intestinal mucosal permeability to 51Cr labeled ethylen diamin tetraacetic acid (51Cr EDTA) was measured by collecting urine samples in metabolic cages for six hours following 24 hours of intestinal obstruction period. After six hours re-laparatomy was performed. Mesenteric lymph nodes and blood samples were cultured to evaluate the bacterial translocation. Ileal tissue samples were harvested to score the histopathological changes and to measure the wet and dry weight differences for calculation of % weight loss. Results: Administration of indomethacine reduced intestinal permeability (3.5±0.10% vs 2.0±0.20%, p

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. Welch JP. General consideration and mortality in bowel obstruction. In: Welch JP, editor. Bowel obstruction: differential diagnosis and clinical management. Philadelphia: Saunders Company; 1990; p. 59-95. 2. Daly JM, Adams JT, Fantini GA, et al. Manifestations of gastrointestinal disease. In: Schwartz SI, editor. Principles of Surgery. 7th ed. New York: Mc Graw Hill Book Co.; 1999; p. 1054-1061. 3. Jones RS. The small intestine. In: Sabiston DC, editor. Textbook of Surgery. 15th ed. Philadelphia: Saunders Company; 1997; p. 909-923 4. Bumin O. Sindirim Sistemi Cerrahisi. Ankara; İlk- San Matbaası, 1986. 5. Maglinte DD, Kelvin FM, Rowe MG, et al. Small-bowel obstruction: Optimizing radiologic investigation and nonsurgical management. Radiology 2001; 218:39-46. 6. Mosley JG, Shoaib A. Operative versus conservative management of adhesional intestinal obstruction. Br J Surg 2000; 87: 362-373. 7. Miller G, Boman J, Shrier I, et al. Readmission for small-bowel obstruction in the early postoperative period: Etiology and outcome. Can J Surg 2002; 45:255-258. 8. Seror D, Feigın E, Szold A, et al. How Conservatively Can Postoperative Small Bowel Obstruction Be Treated? Am J Surg 1993; 165:121-125. 9. Entee MG, Pender D, Mulvin D, et al. Current spectrum of intestinal obstruction. Br J Surg 1987; 74:976-980. 10. Mulvihill SJ, Pappas TN, Fonkalsrud EW, et al. Effect of somatostatin on experimental intestinal obstruction. Ann Surg 1988; 207:169-173. 11. Nelson TW, Ellis H. The spesctrum of intestinal obstruction today. B J Clin Pract 1984; 38:249-251. 12. Nellgard P, Cassuto J. Inflamation as a major cause of fluid losses in small bowel obstruction. Scand J Gastroenterol 1993; 28:1035- 1041. 13. Gittes GK, Nelson TM, Debas HI, et al. Improvement in survival of mice with proximal small bowel obstruction treated with octreotide. Am J Surg 1992; 163:231-233. 14. Quioque T, Gliek SN. Inflamatory changes proximal to obstructing lesions in the small intestine. Gastrointest Radiol 1985; 10:157-160. 15. Dirosa M, Giround JP, Wiloughby DA. Studies of the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine. J Pathol 1971; 104:15-29. 16. Roscher R, Oettinger W, Beger HG. Bacterial microflora, endogenous endotoxin, and prostaglandins in small bowel obstruction. Am J Surg 1988; 155:348-355. 17. Bukhave K, Rask MJ. Prostaglandin E2 in jejunal fluids and its diagnostic value for selecting patients with indomethacin sensitive diarrhoea. Eur J Clin Invest 1981; 11:191-197. 18. Beubler E, Kollar G, Sarıa A, et al. Involvement of 5 hydroxytryptamine, prostaglandin E2 and cyclic adenosine monophosphate in cholera toxin induced fluid secretion in the small intestine of the rat in vivo. Gastroenterology 1989; 96:368- 376. 19. Nellgard P. Jonsson A, Bojo L, et al. Small-bowel obstruction and the effects of lidocaine, atropine and hexamethonium on inflammation and fluid losses. Acta Anaesthesiol Scand 1996; 40:287-292. 20. Sagar PM, Macfie J, Sedman P, et al. Intestinal obstruction promotes gut translocation of bacteria. Dis Colon Rectum 1995; 38:640-644. 21. Akcay MN, Capan MY. Gundogdu C, et al. Bacterial translocation in experimental intestinal obstruction. J Int Med Res 1996; 24:17-26. 22. Doig CJ, Sutherland LR, Sandham JD, et al. Increased intestinal permeability is associated with the development of multiple organ dysfunction syndrome in critically ill ICU patients. Am J Respir Crit Care Med 1998; 158:444-451. 23. Deitch EA. Simple intestinal obstruction causes bacterial translocation in man. Arch Surg 1989; 124:699-701. 24. Kayaalp SO. Tıbbi Farmakoloji. 8th ed. Ankara: Taş Kitabevi; 1998. 25. Donald GP, John HK. Non-steroid antienflamatuvar ilaçlar; Opioid olmayan analjezikler; Gutta kullanılan ilaçlar. In: Katzung BG editor. Temel ve Klinik Farmakoloji. 6th ed. İstanbul: Barış Kitabevi; 1995; p. 710-743. 26. Wallace JL, Cirino G. The development of gastrointestinal sparing nonsteroidal anti-inflammatory drugs. Trends Pharmacol Sci 1994; 15:405-406. 27. Yamada D, Deitch E, Specian RD, et al. Mechanisms of acute and chronic intestinal inflammation induced by indomethacin. Inflammation 1993; 17:641-662. 28. Reuter BK, Davies NM, Wallace JL. Nonsteroidal antiinflammatory drug enteropathy in rats: Role of permeability, bacteria and enterohepatic circulation. Gastroenterology 1997; 112:109-17. 29. Edwin AD, William MB. Jing WM, et al. Obstructed intestine as a reservoir for systemic infection. Am J Surg 1990; 159:394-401. Journal of Ankara University Faculty of Medicine 2006; 59(3) A. Demirkan, M. Aksoy, M. A. Kuzu, A. Törüner 127 30. Mac Gregor IL, Lavigne ME. Inhibition by indomethacin of intestinal distension induced secretion in the rat. J Surg Res 1979; 26:167-170. 31. Mizoguchi H, Ease S, Tanaka A, et al. Lack of small intestinal ulcerogenecity of nitric oxide-releasing indomethacin, NCX-530, in rats. Aliment Pharmacol Ther 2001; 15:257-267. 32. Bjarnason I, Macpherson A, Hollander D. Intestinal permeability: An overview. Gastroenterology 1995; 108:1566-1581. 33. Reis E, Kama NA, Coskun T, et. al. Effects of octreotide and a-tocopherol on bacterial translocation in experimental intestinal obstruction: a microbiological, light and electronmicroscopical study. Hepatogastroenterology 1997; 44: 656-663. 34. Conover WJ. Practical Nonparametric Statistics. 2nd ed. New York: John Wiley & Sons; 1980. 35. Edwin AB. The role of intestinal barrier failure and bacterial translocation in the development of systemic infection and multiple organ failure. Arch Surg 1990; 125:403-405. 36. Deitch EA. Does the gut protect or injures patients in the ICU? Perspectives in Critical Care. St Louis, Mo: Quality Medical Publishing Inc; 1988; 1:15-32. 37. Deitch EA. Infection in the compromised host. Surg Clin North Am 1988; 68: 181-197. 38. Cohn I Jr. Strangulation obstruction: Antibiotic protection. Sur gery 1956; 39:630-641. 39. Deitch EA, Maejima K, Berg RD. Effect of oral antibiotics and bacterial overgrowth on the translocation of the GI-tract microflora in burned rats. J Trauma 1987; 25:385-392. 40. Deitch EA, Berg RD, Specian R. Endotoxin promotes the translocation of bacteria from the gut. Arch Surg 1987;122: 185-390. 41. Bishop RF, Allcock EA. Bacterial flora of the small intestine in acute intestinal obstruction. Br Med J 1960; 1:413-416. 42. Deitch EA. Simple intestinal obstruction causes bacterial translocation in man. Arch Surg 1989; 124:699-701. 43. Sedman PC, Macfie J, Sagar P, et al. The prevalence of gut translocation in humans. Gastroenterology 1994; l07: 643-439. 44. Akin ML, Uluutku H, Erenoğlu C, et al. Hyperbaric oxygen ameliorates bacterial translocation in rats with mechanical intestinal obstruction. Dis Colon Rectum. 2002; 45:967-972. 45. Chappuis CW, Cohn I Jr. Intestinal obstruction. In: Fielding ML, Welch PJ, Moore FD. editors. Clinical Surgery. London: Churchill Livindstone; 1987; p. 32-40. 46. Fujii E, Irie K, Ogawa A, et al. Role of nitric oxide and prostaglandins in lipopolysaccharide-induced increase in vascular permeability in mouse skin. Eur J Pharmacol 1996; 297: 257-63. 47. Granger DN, Barrowman JA. Microcirculation of the alimentary tract. Gastroenterology 1983; 84:1035-1049. 48. Dabareiner RM, Sullins KE, Snyder JR. Evaluation of the microcirculation of the equine small intestine after intralurninal disten tion and subsequent decompression. Am J Vet Res 1993; 54:1673-1682. 49. Moore JN, Allen D, Clark SE. The pathophysiology of colic. In: Gordon BJ, Allen D, editors. Colic management in the horse. Lenexa, Kan: Veterinary Medicine Publishing Co.: 1988; p. 101-119. 50. Synder JR. The pathophysiology of intestinal damage: effects of luminal distention and ischemia.Vet Clin North Am Equine Pract 1989; 5:247-70. 51. Lundin C, Sullins KE, White NA. Induction of peri toneal adhesions with small intestinal ischemia and distention in the foal. Equine Vet J 1989;21:451-558. 52. Öhman U. Studies on small intestinal obstruction. I. Intra luminal pressure in experimental low small bowel obstruction in cat. Acta Chir Scand l975; 141:413-416. 53. Dabareıner RM, White NA, Donaldson LL, Effects of intraluminal distention and decompression on microvascular permeability and hemodynamics of the equine jejunum Am J Vet Res 2001; 62:225-236 54. Champion DG, Feng PH, Azurna T, et al. NSAID induced gastrointestinal damage. Epidemiology, risk and prevention with an Evaluation of the role of misoprostol. Drugs 1997; 53:6-19. 55. Sigthorsson G, Tibble J, Hayllar J, et al. Intestinal permeability and inflammation in patients on NSAIDs. Gut 1998; 43:506-511. 56. Tibble JA, Sigthorsson G, Foster R, et al. Comparison of the Intestinal Toxicity of Celecoxib, a Selective COX-2 Inhibitor, and Indomethacin in the Experimental Rat. Scand J Gasrtoenterol 2000; 35:802-807.