Oktay BOSNALI, Akgün ORAL, Elif DEMİRCİ, FAZLI ERDOĞAN, Bedii SALMAN

Ratlarda alkali özefagus yanığı üzerine aprotinin’in antienflamatuar etkileri

Amaç: Çalışmamızda; ratlarda alkali ile oluşturduğumuz özefagus yanığı modelinde aprotininin antienflamatuar etkisinin olup olmadığı araştırılmıştır. Gereç ve yöntem: Ratlardaki özefagus yanığı, Gehanno’nun tarif ettiği yöntem kullanılarak, %5 NaOH ile irigasyon yapılarak oluşturuldu. Çalışmamızda 56 adet (150–220 gr) rat kullanıldı ve bu ratlar dört ana gruba ayrıldı: Kontrol Grubu, 12 adet zarar görmemiş rat; sham grubu, 12 adet sham operasyonu yapılmış rat; Özefagus yanığı grubu, 16 adet Özefagus yanığı yapılmış ama tedavi almamış rat; Özefagus yanığı aprotinin tedavi grubu, 16 adet özefagus yanığı olan ve intraperitoneal aprotinin tedavisi alan rat. Tüm gruplar, aprotinin’in kostik özefagus yanığından sonraki 1’inci, 3’üncü, 7’inci ve 15’inci günlerdeki antienflamatuar etkilerinin karşılaştırmalı olarak incelenmesi için, yanıktan sonraki aynı günlere karşılık gelen dört alt-gruba ayrıldı. Tüm gruplarda histopatolojik inceleme yapıldı ve yanığın ağırlığı, submukozal kollajen depolanmasında artış, muskularis mukoza hasarı ve tunika muskularisteki hasar ile tunika muskulariste kollajen depolanması açısından semi-kantitatif olarak incelendi. Bulgular: Kostik özefagus yanığı, özefagus yanığı ve özefagus yanığı aprotinin tedavi grubundaki tüm ratlarda elde edildi. Fakat, lökosit birikmesi olarak ifade edilen enflamatuar cevap, Özefagus yanığı aprotinin tedavi grubu ratların, kostik yanıktan sonraki 1’inci, 7’inci ve 15’inci gün subgruplarında istatistiki olarak anlamlı derecede düşük idi (p

Antiinflamatory effects of aprotinin on alkali burns of the esophagus in rats

Objective: In this study we investigated whether aprotinin has antiinflammatory effects on alkali esophageal burn model in rats. Material and method: Caustic esophageal burns were produced in rats by irrigation with 5% NaOH as described by Gehanno. In this study fifty-six rats (150-220 gr) were used. Rats were divided into four main groups as follows; control group, 12 rats, uninjured; sham group, 12 rats with sham operation; esophageal burn group, 16 rats with esophageal burns, received no treatment; esophageal burn aprotinin treatment group, 16 rats with esophageal burns, received intraperitoneal aprotinin treatment. All groups were divided into four subgroups as 1st, 3rd, 7th and 15th day after the caustic burn subgroups to comparison the anti-inflammatory effects of aprotinin on the corresponding days. Histopathologic evaluation was performed in all groups, and severity of the burn, increase in submucosal collagen deposition, damage to muscularis mucosa, and damage and collagen deposition in tunica muscularis was analyzed semi-quantitatively. Results: Caustic esophageal burn was encountered in all esophageal burn and esophageal burn aprotinin treatment groups, but the inflammatory response expressed as leukocyte accumulation was statisticly lower in the 1st, 7th and 15th day after caustic burn subgroups of esophageal burn aprotinin treatment group rats (p<0.05). In the 7th and 15th day after caustic burn subgroups, collagen deposition in tunica muscularis was statisticly lower in esophageal burn aprotinin treatment group than esophageal burn group rats (p<0.05). Conclusion: Aprotinin seems to limit inflammatory response which caused by caustic esophageal burn.

PDF

___

1. Millar AJW, Numanoglu A, Rode H. Caustic strictures of the Esophagus. In Grosfeld JL, O’Neill JA Jr., Eric Fonkalsrud., et al (eds): Pediatric Surgery. Philedelphia, PA, Mosby-Elsevier, 2006; 1082–1092.
2. Bingol-Kologlu M, Tanyel FC, Muftuoglu S, et al. The preventive effect of heparin on stricture formation after caustic esophageal burns. J Pediatr Surg 1999;34:291- 294.
3. Hamza AF, Abdelhay S, Sherif H, et al. Caustic esophageal strictures in children: 30 years' experience. J Pediatr Surg 2003;38:828-833.
4. Bautista CA, Estevez Martinez E, Varela Cives R et al. A retrospective analysis of ingestion of caustic substances by children. Ten-year statistics in Galicia. Eur J Pediatr 1997; 156:410-414.
5. Gunel E, Caglayan F, Caglayan O et al. Effect of antioxidant therapy on collagen synthesis in corrosive esophageal burns. Pediatr Surg Int 2002; 18:24-27.
6. Kiyan G, Aktas S, Ozel K et al. Effects of Hyperbaric Oxygen Therapy on Caustic Esophageal Injury in Rats. J Pediatr Surg 2004;39:1188-1193.
7. Pelclová D, Navrátil T. Do corticosteroids prevent oesophageal stricture after corrosive ingestion? Toxicol Rev 2005 24:125-129.
8. Bautista A, Tojo R, Varela R et al. Effects of Prednisolone and Dexamethasone on alkali burns of the esophagus in Rabbit. J Pediatr Surg 1996;22:275-283.
9. Ozcelik MF, Pekmezci S, Saribeyoglu K et al. The effect of halofuginone, a specific inhibitor of collagen type 1 synthesis, in the prevention of esophageal strictures related to caustic injury. Am J Surg 2004;187:257-260.
10. Yagmurlu A, Aksu B, Kologlu MB et al. A novel approach for preventing esophageal stricture formation: sphingosylphosphorylcholine- enhanced tissue remodeling. Pediatr Surg Int 2004; 20: 778-782.
11. Koltuksuz U, Mutus HM, Kutlu R, et al. Effects of caffeic acid phenethyl ester and epidermal growth factor on the development of caustic esophageal stricture in rats. J Pediatr Surg 2001; 36:1504-1509 .
12. Weiss SJ. Tissue destruction by neutrophils. N Engl J Med 1989; 320:365-376.
13. Eppinger MJ, Deeb GM, Bolling SF et al. Mediators of ischemia-reperfusion of rat lung. Am J Pathol 1997;150: 1773-1784.
14. Landis RC, Asimakopoulos G, Poullis M et al. The antithrombotic and antiinflammatory mechanisms of action of aprotinin. Ann Thorac Surg 2001; 72:2169-2175.
15. Pruefer D, Makowski J, Dahm M, et al. Aprotinin inhibits leukocyte-endothelial cell interactions after hemorrhage and reperfusion. Ann Thorac Surg 2003 75:210-215; discussion 215-216.
16. Ozel SK, Dagli TE, Yuksel M et al. The roles of free oxygen radicals, nitric oxide, and endothelin in caustic injury of rat esophagus. J Pediatr Surg 2004; 39:1381-1385.
17. Cadranel S. Treatment of esophageal caustic injuries: experience with high-dose dexhamethasone. Pediatr Surg Int 1993; 8:97-101.
18. Gunel E, Caglayan F, Caglayan O et al. Reactive oxygen radical levels in caustic esophageal burns. J Pediatr Surg 1999; 34:405-407.
19. Till GO, Guilds LS, Mahrougui M et al. Role of xhantine oxidase in thermal injury of skin. Am J Pathol 1989; 135: 195-202.
20. Kiyan G, Aktas S, Ozel K et al. Effects of Hyperbaric Oxygen Therapy on Caustic Esophageal Injury in Rats. J Pediatr Surg 2004; 39:1188-1193.
21. Bautista A, Tojo R, Varela R et al. Effects of Prednisolone and Dexamethasone on alkali burns of the esophagus in Rabbit. J Pediatr Surg 1996; 22:275-283.
22. Guven A, Gundogdu G, Sadir S et al. The efficacy of ozone therapy in experimental caustic esophageal burn. J Pediatr Surg 2008; 43:1679-1684.
23. Uguralp S, Irsi C, Aksoy T et al. Resveratrol attenuates inflammation and stricture formation in experimental caustic esophageal burns. Pediatr Surg Int 2008; 24:425-430.
24. Makay O, Yukselen V, Vardar E et al. Role of allopurinol on oxidative stress in caustic burn: cure for stricture? Pediatr Surg Int. 2007; 23:1105-1112.
25. Türkyilmaz Z, Sönmez K, Karabulut R et al. Mitomycin C decreases the rate of stricture formation in caustic esophageal burns in rats. Surgery 2009; 145:219-225.
26. Yukselen V, Karaoglu AO, Ozutemiz O et al. Ketotifen ameliorates development of fibrosis in alkali burns of the esophagus. Pediatr Surg Int 2004; 20:429-433.
27. Yukselen V, Karaoglu AO, Yenisey C et al. Trimetazidine reduces the degree of fibrosis in alkali burns of the esophagus. J Pediatr Surg 2005; 40:505-509.
28. Ekingen G, Ozden M, Sözübir S et al. Effect of the prostacyclin derivate iloprost in experimental caustic esophageal burn.. Pediatr Surg Int 2005; 21:441-444.
29. Temir ZG, Karkiner A, Karaca I et al. The effectiveness of sucralfate against stricture formation in experimental corrosive esophageal burns. Surg Today 2005; 35:617- 622.
30. Bingol-Kologlu M, Tanyel FC, Muftuoglu S et al. The preventive effect of heparin on stricture formation after caustic esophageal burns. J Pediatr Surg 1999; 34:291- 294.
31. Watchfogel YT, Kucich U, Hack CE et al. Aprotinin inhibits the contact, neutrophil, and platelet activation systems during simulated extracorporeal perfusion. J Thorac Cardiovasc Surg 1993; 106:1-10.
32. Asimakopoulos G, Thompson R, Noursharg S et al. An anti–inflammatory property property of aprotinin discovered at the level of leukocyte extravasation. J Thorac Cardiovasc Surg 2000; 120:361-369.
33. Hill GE, Alonso A, Spurzem JR et al. Aprotinin and methylprednisolone equally blunt neutrophil cardiopulmonary by-pass induced inflammation in humans. J Thorac Cardiovasc Surg 1995; 110:1658-1662.
34. Broche F, Romero A, Olembe E et al. Aprotinin mediated antioxidant effect in Cardiosurgery with mechanical cardiorespiratory support (CMCS). J Cardiovasc Surg 2002; 43:429-436.
35. Landis RC, Haskard DO, Taylor KM. New anti-inflammatory and platelet-preserving effects of aprotinin. Ann Thorac Surg 2001; 72:1808-1813.
36. Asimakopoulos G, Lidington E, Mason JC et al. Effect of Aprotinin on endothelial cell activation. J Thorac Cardiovasc Surg 2001; 122:123-128.
37. Cejkova J, Lodja Z, Salonen E-M et al. Histochemical study of alkali-burned rabbit anterior eye segment in which severe lesions were prevented by aprotinin treatment. Histochemistry 1989; 92:441-448.
38. Yilmaz T, Kukner AS, Aydemir O et al. Aprotinin reduces ischemia-reperfusion injury in the retina of guinea pigs. Eur J Ophthalmol 2003; 13:642-647.
39. Royston D, van Haaften N, De Vooght P. Aprotinin; friend or foe? A review of recent medical literature. Eur J Anaesthesiol 2007; 24:6-14. Review.
40. Dietrich W. Aprotinin: 1 year on. Curr Opin Anaesthesiol. 2009; 22:121-127. Review.
41. Takagi H, Manabe H, Kawai N et al. Aprotinin increases mortality as compared with tranexamic acid in cardiac surgery: a meta-analysis of randomized head-to-head trials. Interact Cardiovasc Thorac Surg 2009;9:98-101.