Effect of Ozone Therapy (OT) on Healing of Colonic Anastomosis in a Rat Model of Peritonitis

Abstract

Background: Ozone is a three-oxygen molecule (O3). Ozone therapy (OT) is systematically effective when pathological inflammatory and immunologic processes are activated. Among of these conditions are wound healing, macular degeneration related to aging, and conditions that are ischemic or infectious. Aims: The aim of this study was to determine the effects of OT on wound healing of intestinal anastomosis in the presence of peritonitis in a rat model. Study Design: Animal experimentation. Methods: A total of 40 Wistar albino rats were randomized into four groups (n=10) including: sham (S), peritonitis (P), ozone 0 (O0), and ozone 24 (O24). In group S, only cecal dissection was carried out. The S group had only a cecal dissection and intestinal anastomosis performed, but no peritonitis. In all other groups, cecal ligation and puncture (CLP) followed the cecal dissection to induce bacterial peritonitis. 24 h after puncture, a cecal resection and ileocolic anastomosis were performed. In group P, 24 h after CLP, a cecal resection and ileocolic anastomosis were performed and no ozone was administered. In group O0, immediately after the anastomosis, and in group O24, starting 24 hours after the anastomosis, an intraperitoneal 1 mg/ kg/day ozone administration was applied for seven days. On the seventh day the animals were sacrificed, the anastomotic bursting pressures (BP) and the hydroxyproline values of the anastomotic tissues were measured, and histopathologic examination of the anastomotic segment was carried out. Results: The highest BP was in group S, with 211±23.13 mmHg. The mean BP of group P was 141±56.25 mmHg, which was significantly lower than in the other two peritonitis groups that received ozone therapy, group O0 and O24, where it was 192±22 and 166±45 mmHg, respectively (p<0.05). The difference in the BP between groups O0 and O24 was not statistically significant (p>0.05). Histopathologic analyses of the anastomotic segments determined there was significantly more oedema and necrosis in the control group rats, and collagen deposition in the anastomotic tissue was significantly higher in the ozone-treated groups on postoperative day 7. Hydroxyproline levels were significantly higher in groups O0 and O24 compared to the peritonitis group (P). Conclusion: Ozone therapy has a beneficial effect on anastomotic healing of the colon in the presence of peritonitis.

Keywords

• Anastomosis, colon, ozone, peritonitis, rat

Kaynakça

1. 1. Vaneerdeweg W, Hendriks JMH, Lauwers PRM, Leven M, Eyskens EJM. Effects of gentamicin-containing sponges on the healing of colonic anastomoses in a rat model of peritonitis. Eur J Sur 2000;166:959-62. [CrossRef]
2. 2. Sakallıoglu AE, Yagmurlu A, Dindar H, Hasırcı N, Renda N, Deveci MS. Sustained local application of low-dose epidermal growth factor on steroidinhibited colonic wound healing. J Pediatr Surg 2004;39:591-5. [CrossRef]
3. 3. Khalili TM, Navarro RA, Middleton Y, Margulies DR. Early postoperative enteral feeding increases anastomotic strength in a peritonitis model. Am J Surg 2001;182:621-4. [CrossRef]
4. 4. Reijnen MMPJ, de Man BM, Hendriks Th, Postma VA, Meis JFGM, van Goor H. Hyaluronic acid-based agents do not affect anastomotic strength in rat colon, in either the presence or absence of bacterial peritonitis. Br J Surg 2000;87:1222-8. [CrossRef]
5. 5. Hubbard WJ, Choudhry M, Schawacha G, Kerby JD, Rue LW 3rd, Bland KI, et al. Cecal ligation and puncture. Shock 2005;24:52-7. [CrossRef]
6. 6. Ozen IO, Ekingen G, Taslıpınar MY, Bukan N, Demirogulları B, Karabulut R, et al. Effect of melatonin on healing of colonic anastomosis in a rat model of peritonitis. Eur Surg Res 2007;39:122-7. [CrossRef]
7. 7. Stubinger S, Sader R, Filippi A. The use of ozone in dentistry and maxillofacial surgery: A review. Quintessence Int 2006;37:353-9.
8. 8. Nogales CG, Ferrari PH, Kantorovich EO, Lage-Marques JL. Ozone therapy in medicine and dentistry. J Contemp Dent Pract 2008;9:75-84.

9. 9. Bocci V. The case for oxygen-ozone therapy. Br J Biomed Sci 2007;64:44-9.
10. 10. Martinez-Sanchez G, Al-Dalain SM, Menendez S, Re L, Giuliani A, Candelario-Jalil E. Therapeutic efficacy of ozone in patients with diabetic foot. Eur J Pharmacol 2005;523:151-61. [CrossRef]
11. 11. Guven A, Gundogdu G, Sadir S, Topal T, Erdogan E, Korkmaz A, et al. The efficacy of ozone therapy in experimental caustic esophageal burn. J Pediatr Surg 2008;43:1679-84. [CrossRef]
12. 12. Lelyanov AD, Sergienko VI, Ivliev NV, Emelyanov VV, Guseva ED. Effects of sodium hypochlorite and ozone on healing of intestinal anastomosis in simulated strangulation colorectal obstruction. Bull Exp Biol Med 2004;137:103-5. [CrossRef]
13. 13. Canbay E, Agachan B, Ozturk T, Giris M, Asoglu O, Balik E, et al. Dual inhibition of wound healing and oxidative process by montelukast in experimental colon anastomoses. Surg Innov 2010;7:248-55. [CrossRef
14. 14. Verhofstad MH, Lange WP, van der Laak JA, Verhofstad AA, Hendriks T. Microscopic analysis of anastomotic healing in the intestine of normal and diabetic rats. Dis Colon Rectum 2001;44:423-31. [CrossRef]
15. 15. Ehrlich HP, Hunt TK.The effects of cortisone and anabolic steroids on the tensile strength of healing wounds. Ann Surg 1969;170:203-6. [CrossRef]
16. 16. Phillips JD, Kim CS, Fonkalsrud EW, Zeng H, Dindar H. Effect of chronic corticosteroid and vitamin A on the healing of intestinal anastomoses. Am J Surg 1992;163:71. [CrossRef]
17. 17. Sumer A, Altınlı E, Senger S, Köksal N, Onur E, Eroğlu E, et al. Effect of pentoxifylline and vinpocetine on the healing of ischemic colon anastomosis: an experimental study. Ulus Travma Acil Cerrahi Derg 2011;17:482-7.
18. 18. Inan A, Sen M, Sürgit O, Ergin M, Bozer M. Effects of the histamine H2 receptor antagonist famotidine on the healing of colonic anastomosis in rats. Clinics (Sao Paulo) 2009;64:567-70. [CrossRef]
19. 19. Guzel S, Sunamak O, AS A, Celik V, Ferahman M, Nuri MM, et al. Effects of hyperbaric oxygen and Pgg-glucan on ischemic colon anastomosis. World J Gastroenterol 2006;12:1421-5.
20. 20. Moran M, Ozmen MM, Duzgun AP, Gok R, Renda N, Seckin S, et al. The effect of erythropoietin on healing of obstructive vs nonobstructive left colonic anastomosis: an experimental study. World J Emerg Surg 2007;2:13. [CrossRef]
21. 21. Cetinkaya Z, Esen K, Ozercan IH, Ustundag B, Ayten R, Ay-gen E. The effect of Bosentan on healing of colonic anastomosis. World J Emerg Surg 2006;1:37. [CrossRef]
22. 22. Caglikulekçi M, Ozcay N, Orugg T, Aydog G, Renda N, Atalay F. The effect of recombinant growth hormone on intestinal anastomotic wound healing in rats with obstructive jaundice. Turk J Gastroenterol 2002;13:17-23.
23. 23. Di Paolo N, Bocci V, Gaggiotti E. Ozone therapy. Int J Artif Organs 2004;27:168-75.
24. 24. Tandara AA, Mustoe TA. Oxygen in wound healing--more than a nutrient. World J Surg 2004;28:294-300. [CrossRef]
25. 25. Aslan MK, Boybeyi Ö, Şenyucel MF,Ayva Ş, Kısa Ü,Aksoy N, et al. Protective effect of intraperitoneal ozone application in experimental ovarian ischemia/reperfusion injury. J Pediatr Surg 2012;47:1730-4. [CrossRef]
26. 26. Teke Z, Aytekin FO, Aydin C, Kabay B, Yenisey C, Sacar S, et al. Effects of pyrrolidine dithiocarbamate on healing of colonic anastomoses in the cecal ligation and puncture model of intraperitoneal sepsis in rats. World J Surg 2007;31:200-9. [CrossRef]
27. 27. Cihan AO, Bicakci U, TanderB, Rizalar R, Kandemir B, Ariturk E, et al. Effects of intraperitoneal nitroglycerin on the strength and healing attitude of anastomosis of rat intestines with ischemia-reperfusion injury. Afr J Paediatr Surg 2011;8:206-10. [CrossRef]
28. 28. Caliskan B, Guven A, Ozler M, Cayci T, Ozcan A, Bedir O, et al. Ozone therapy prevents renal inflammation and fibrosis in a rat model of acute pyelonephritis. Scand J Clin Lab Invest 2011;71:473-80. [CrossRef]
29. 29. Skurska A, Pietruska MD, Paniczko-DrezekA, Dolinska E, ZelazowskaRutkowska B, Zak J, et al. Evaluation of the influence of ozonotherapy on the clinical parameters and MMP levels in patients with chronic and aggressive periodontitis. Adv Med Sci 2010;55:297-307. [CrossRef]