Effects of Ozonated Olive Oil on Acute Radiation Proctitis in Rats

Abstract

Background: Acute radiation proctitis is a common complication of pelvic radiation and management of acute radiation proctitis is under evaluation. The beneficial effects of ozonated olive oil (OzOO) have already been shown in the treatment of chronic wounds. Thus, this study was designed to evaluate the therapeutic effects of topical OzOO on acute radiation proctitis. Aims: To evaluate the therapeutic effects of topical OzOO on acute radiation proctitis. Study Design: Animal experimentation. Methods: Rats were divided into three groups: control; irradiation+saline (1 mL); and irradiation +OzOO (1 mL). A single fraction of 17.5 Gy was delivered to each rat. The OzOO was administered rectally each day after irradiation. Each rat was observed daily for signs of proctitis. Irradiated rats were euthanised on days 5 and 10. The mucosal changes were evaluated macroscopically and pathologically. Results: According to the clinical findings, five rats in the irradiation+saline group showed Grade 4 symptoms on the 10th day. Macroscopic finding scores on the 10th day in the irradiation+saline and irradiation+OzOO groups were statistically significantly different. On pathological examination, radiation-induced mucosal damage was the most prominent 10 days after irradiation in saline-treated rats. On the 10th day, the irradiation+OzOO group showed mild inflammation and slight crypt change, which corresponded to Grade 1 pathological findings. Conclusion: OzOO attenuates macroscopic and pathological findings of acute radiation proctitis in rats. Turkish Başlık:Ozonlanmış Zeytinyağının Ratlarda Akut Radyasyon Proktiti Üzerine Etkisi Anahtar Kelimeler:Ozonlanmış zeytinyağı, radyasyon proktiti Arkaplan: Pelvik radyoterapinin en yaygın komplikasyonu olan akut radyasyon proktiti olup tedavi yöntemi halen incelenmektedir. Günümüzde ozonlanmış yağların etkinliği, diabet veya ateroskleroza bağlı gelişen ülserlerde ve travma ve yanıklar sonrasında meydana gelen yaralarda gösterilmiştir. Amaç: Çalışmada radyasyon proktiti oluşturulan ratlarda ozonlanmış zeytinyağının (OzZY) topikal kullanımının akut dönemde etkilerinin incelenmesi amaçlanmıştır. Çalışma Tasarımı: Hayvan deneyi. Yöntemler: Otuz beş Wistar Albino rat 3 gruba ayrıldı: kontrol grubu, radyasyon (R)+ saline (1 mL) grubu ve R+ ozonlanmış zeytinyağı (OzZY) (1 mL) grubu. Tek fraksiyon 17.5 Gy ışınlama sonrasında saline ve OzZY günde 2 kez olacak şekilde rektal yolla uygulandı. Her ratta günlük olarak proktit bulguları takip edildi. Klinik bulgular; 0: semptom yok, 2: diyare, 4: aşikar kanama olacak şekilde skorlandı. Her gruptan 7 rat 5 ve 10. günlerde sakrifiye edildi. Mukozal değişiklikler patolojik olarak değerlendirildi. Sonuçlar 0'dan 4'e hafif ve çok şiddetli olarak derecelendirildi. Bulgular: Diğer gruplarla karşılaştırıldığında 10. günde sakrifiye edilen R+saline grubundaki ratların %74.1 oranında grade 4 klinik semptom skoru gösterdiği tespit edildi. OzZY tedavisinin aşikâr kanamayı önlediği tespit edildi. Klinik semptom skorları açısından R+Saline ve R+OzZY grupları arasındaki fark istatiksel olarak anlamlı bulundu. Patolojik incelemeye göre radyasyonun indüklediği mukozal hasar en yoğun olarak 10. gün R+saline grubunda % 85,7 oranında grade 3 ve %14, oranında da grade 4 olarak izlendi. OzZY verilen ratlarda grade 4 patolojik bulgulara rastlanmadı. 10. gün R+ OzZY grubunda hafif inflamasyon ve önemsiz kriptik değişikliklerin olduğu grade 1 patolojik bulguların olduğu tespit edildi. Sonuç: Bu çalışmada OzZY tedavisinin ratlarda akut radyasyon proktiti semptomlarını ve patolojik bulgularını azalttığı gözlenmiştir.

Keywords

• Ozonated olive oil, radiation proctitis

Effects of Ozonated Olive Oil on Acute Radiation Proctitis in Rats

Öz

Kaynakça

1. Hauer-Jensen M, Wang J, Denham JW. Bowel injury: current and evolving management strategies. Semin Radiat Oncol 2003;13:357-71.
2. Hovdenak N, Fajardo LF, Hauer-Jensen M. Acute radiation proctitis:a sequential clinicopathologic study during pelvic radiotherapy. Int J Radiat Oncol Biol Phys 2000;48:1111-7. [CrossRef] Korkut C, Asoglu O, Aksoy M, Kapran Y, Bilge H, Kiremit-Korkut N, et al. Histopathological comparison of topical therapy modalities for acute radiation proctitis in an experimental rat model. World J Gastroenterol 2006;12:4879-83.
3. Sherman LF, Prem KA, Mensheha NM. Factitial proctitis: A restudy at the University of Minesota. Dis Colon Rectum 1971;14:281-5. [CrossRef]
4. Kneebone A, Mameghan H, Bolin T, Berry M, Turner S, Kearsley J, et al. Effect of oral sucralfate on late rectal injury associated with radiotherapy for prostate cancer: A double-blind, randomized trial. Int J Radiat Oncol Biol Phys 2004;60:1088-97. [CrossRef]
5. Kochhar R, Patel F, Dhar A, Sharma SC, Ayyagari S, Aggarwal R, et al. Radiation-induced proctosigmoiditis:Prospective, randomized, double-blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate. Dig Dis Sci 1991;36:103-7. [CrossRef]
6. Cavcic J, Turcic J, Martinac P, Jelincic Z, Zupancic B, PanijanPezerovic R, et al. Metronidazole in the treatment of chronic radiation proctitis: Clinical trial. Croat Med J 2000;41:314-8.
7. Tsujinaka S, Baig MK, Gornev R, de la Garza C, Hwang JK, Sands D, et al. Formalin instillation for hemorrhagic radiation proctitis. Surg Innov 2005;12:123-8. [CrossRef]
8. Parikh S, Hughes C, Salvati EP, Eisenstat T, Oliver G, Chinn B, et al. Treatment of hemorrhagic radiation proctitis with 4 percent formalin. Dis Colon Rectum 2003;46:596-600. [CrossRef]

9. Karamanolis G, Triantafyllou K, Tsiamoulos Z, Polymeros D, Kalli T, Misailidis N, et al. Argon plasma coagulation has a long-lasting therapeutic effect in patients with chronic radiation proctitis. Endoscopy 2009;41:529-31. [CrossRef]
10. Ventrucci M, Di Simone MP, Giulietti P, De Luca G. Efficacy and safety of Nd:YAG laser for the treatment of bleeding from radiation proctocolitis. Dig Liver Dis 2001;33:230-3. [CrossRef]
11. Nakabayashi M, Beard C, Kelly SM, Carr-Locke DL, Oh WK. Treatment of a radiation-induced rectal ulcer with hyperbaric oxygen therapy in a man with prostate cancer. Urol Oncol 2006;24:503 [CrossRef]
12. Allen S, Kilian C, Phelps J, Whelan HT. The use of hyperbaric oxygen for treating delayed radiation injuries in gynecologic malignancies: a review of literature and report of radiation injury incidence. Support Care Cancer 2012;20:2467-72. [CrossRef]
13. Bocci V. Ozone: A New Medical Drug. Dordrecht: Springer, 2005;32-5, 102-3.
14. Oosting RS, Van Rees-Verhoef M, Verhoef J, Van Golde LM, Van Bree L. Effects of ozone on cellular ATP levels in rat and mouse alveolar macrophages. Toxicology 1991;70:195-202. [CrossRef]
15. Kan S, Chun M, Jin YM, Cho MS, Oh YT, Ahn BO, et al. A rat model for radiation-induced proctitis. J Korean Med Sci 2000;15:682-9.
16. Northway MG, Scobey MW, Geisinger KR. Radiation proctitis in the rat. Sequential changes and effects of anti-inflammatory agents. Cancer 1988;62:1962-9. [CrossRef]
17. Denton AS, Forbes A, Andreyev J, Maher EJ. Non-surgical interventions for late radiation proctitis in patients who have received radical radiotherapy to the pelvis. Cochrane Database Syst Rev 2002;CD003455.
18. Denton AS, Andreyev HJ, Forbes A, Maher EJ. Systematic review for non-surgical interventions for the management of late radiation proctitis. Br J Cancer 2002;8:134-43. [CrossRef]
19. Cotti G, Seid V, Araujo S, Souza AH Jr, Kiss Dr, Habr-Gama A. Conservative therapies for hemorrhagic radiation proctitis:a review. Rev Hosp Clin Fac Med Sao Paulo 2003;58:284-92. [CrossRef]
20. 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]
21. Martínez-Sánchez G, Al-Dalain SM, Menéndez S, Re L, Giuliani A, Candelario-Jalil E, et al. Therapeutic efficacy of ozone in patients with diabetic foot. Eur J Pharmacol 2005;523:151-61. [CrossRef] Clavo B, Gutierrez D, Martin D, Suarez G, Hernandez MA, Robaina F. Intravesical ozone therapy for progressive radiation-induced hematuria. J Altern Complement Med 2005;11:539-41. [CrossRef]
22. Leon OS, Menendez S, Merino N, Castillo R, Sam S, Perez L, et al. Ozone oxidative preconditioning:a protection against cellular damage by free radicals. Mediators Inflamm 1998;7:289-94. [CrossRef]
23. Gultekin FA, Bakkal BH, Guven B, Tasdoven I, Bektas S, Can M, et al. Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats. J Radiat Res 2013;54:36-44. [CrossRef]
24. Clavo B, Ceballos D, Gutierrez D, Rovira G, Suarez G, Lopez L, et al. Long-term control of refractory hemorrhagic radiation proctitis with ozone therapy. J Pain Symptom Manage 2013;46:106-12. [CrossRef] Doi H, Kamikonya N, Takada Y, Fujiwara M, Tsuboi K, Inoue H, et al. Efficacy of polaprezinc for acute radiation proctitis in a rat model. Int J Radiat Oncol Biol Phys 2011;80:877-84. [CrossRef]
25. Yoon WS, Kim CY, Yang DS, Park YJ, Park W, Ahn YC, et al. Protective effect of triphala on radiation induced acute intestinal mucosal damage in Sprague Dawley rats. Indian J Exp Biol 2012;50:195-200.
26. Liu Y, Kudo K, Abe Y, Hu DL, Kijima H, Nakane A, et al. Inhibition of transforming growth factor-beta, hypoxia-inducible factor-1alpha and vascular endothelial growth factor reduced late rectal injury induced by irradiation. J Radiat Res 2009;50:233-9. [CrossRef]
27. Kim HS, Noh SU, Han YW, Kim KM, Kang H, Kim HO, et al. Therapeutic effects of topical application of ozone on acute cutaneous wound healing. J Korean Med Sci 2009;24:368-74. [CrossRef]
28. Valacchi G, Lim Y, Belmonte G, Miracco C, Zanardi I, Bocci V, et al. Ozonated sesame oil enhances cutaneous wound healing in SKH1 mice. Wound Repair Regen 2011;19:107-15. [CrossRef]