Ozon gazının tıbbi amaçlı kullanılması

Ozon (O3) üç oksijen atomundan oluşan renksiz, keskin kokulu doğal bir gazdır. Yer yüzeyi yakınlarında toksik ve kirletici olan ozon, stratosfer tabakasında zararlı ultraviyole ışınları süzücü rolüyle hayati önem taşır. Keşfinden sonraki ilk yıllarda dezenfeksiyon amacıyla kullanılırken yıllar içerisinde yapılan çalışmalar medikal kullanımını gündeme getirmiştir. Ozon tedavisi belirli bir miktarda ozon/oksijen karışımının vücut boşluklarına ya da dolaşım sistemine uygulanması olarak özetlenebilir. Ozon/oksijen gaz karışımı intravenöz, intramuskuler, intraartiküler, intraplevral, intrarektal ve intradiskal uygulanabildiği gibi topikal de uygulanabilir. En yaygın ozon uygulanma şekli majör otohemoterapidir. Bu yöntemde hastadan özel bir şişe içerisine alınan 50–270 ml kan ozon/oksijen karışımı ile belirli bir süre temas ettirilir ve daha sonra tekrar vücuda geri verilir (reinfüzyon). Ozon uygulaması esnasında oksidatif stres ve lipid oksidayonu sonucu oluşan hidrojen peroksit ikincil haberci gibi davranarak ozon tedavisinin biyolojik etkilerine aracılık eder. Tekrarlayan ozon uygulamaları sonucunda antioksidan sistem uyarılarak oksidatif strese karşı direnç gelişir. Ayrıca hücre membranında bulunan yağ asitlerinin oksidasyonuna bağlı olarak çeşitli sitokin düzeyleri de artar. Ozon tedavisi özellikle inflamatuar sürecin yoğun olarak yaşandığı ve immün sistemin ön planda yer aldığı fizyopatolojik durumlarda yardımcı tedavi yöntemi olarak kullanılmaktadır. Bu durumlardan bazıları yara iyileşmesi, yaşa bağlı makuler dejenerasyon, iskemik ve infeksiyöz hastalıklardır.

The use of ozone gas for medical purposes

Ozone (O3) is a colorless and sharp odorous natural gas that is composed of three oxygen atoms. Ozone, that is toxic and pollutant near earth’s surface, it is vital in stratosphere by absorbing harmful ultraviolet radiation. Although initial years after being discovered it was used for disinfection, studies conducted have come into question for medical usage of ozone. Ozone therapy may be summarized as administering a particular amount of ozone/oxygen mixture into body cavities or circulation. Ozone/oxygen gas mixture can be applied via intravenous, intramuscular, intraarticular, intrapleural, intrarectal and intradiscal as well as topically. Most frequent ozone administration is major autohemotherapy. In this method, 50-270 ml blood of patient is taken into a special bottle and after contacting with ozone/oxygen mixture for a particular duration, it is re-infused. During this period, hydrogen peroxide produced by oxidative stress and lipid oxidations mediates the biological effects of ozone therapy by acting as a second messenger. Repetition of ozone administration creates resistance against oxidative stress via inducing antioxidative system. Moreover, levels of several cytokine are increased depending on the fatty acid oxidation in cell membranes. Ozone therapy is used as an adjuvant therapeutic modality in the pathophysiological conditions where severe inflammatory processes and immune activation are involved. Some of the examples are wound healing, age-dependent macular degeneration, ischemic and infectious disorders.

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1. Jacqueline IK. Kirk-Othmer encyclopedia of chemical tecnology. 3rd ed. John Wiley & Sons, 1981.
2. Bocci V. Ozone as Janus: this controversial gas can be either toxic or medically useful. Mediators Inflamm. 2004; 13(1): 3-11.
3. Bocci V. Scientific and medical aspects of ozone therapy. state of the art. Archives of Medical Research. 2006; 37: 425–435.
4. Rowland FS. Stratospheric ozone depletion. Phil Trans R Soc B. 2006; 361: 769-790.
5. Wright ES, Dziedzic D, Wheeler CS. Cellular, biochemical and functional effects of ozone: new research and perspectives on ozone health effects. Toxicol Lett. 1990; 51(2): 125-45.
6. Sanhueza PA, Reed GD, Davis WT, Miller TL. An environmental decision-making tool for evaluating ground-level ozone-related health effects. J Air Waste Manag Assoc. 2003; 53(12): 1448-59.
7. Bocci V. Oxygen-ozone therapy: a critical evaluation. Springer, 2002, p.1-8.
8. Rubin MB. The hıstory of ozone. Bull Hist Chem. 2001; 26(1): 40-56.
9. Wolff HH. Die Behandlung peripherer Durchblutungsstörungen mit Ozon. Erfahr-Heilkd. 1974; 23: 181-184.
10. Travagli V, Zanardi I, Silvietti A, Bocci V. Physicochemical investigation on the effects of ozone on blood. International Journal of Biological Macromolecules. 2007; 4: 1504-511.
11. Pryor WA, Squadrito GL, Friedman M. The cascade mechanism to explain ozone toxicity: the role of lipid ozonation products. Free Radic Biol Med. 1995; 19(6): 935-41.
12. Di Paolo N, Gaggiotti E, Galli F. Extracorporeal blood oxygenation and ozonation: clinical and biological implications of ozone therapy. Redox Rep. 2005; 10(3): 121-30.
13. Mustafa MG. Biochemical basis of ozone toxicity. Free Radical Biol Med. 1990; 9: 245-265.
14. Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radical Biol Med. 1991; 11: 81-128.
15. Hamilton RF, Eschenbacher WL, Szweda L, Holian A. Potential involvement of 4-hydroxynonenal in the response of human lung cells to ozone. Am J Physiol. 1998; 274: L8–L16.
16. Schaur RJ. Basic aspects of the biochemical reactivity of 4-hydroxynonenal. 2003; 24: 149-159.
17. Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P. Redox regulation of cell survival. Antioxid Redox Signal. 2008; 10(8): 1343-74.
18. Korkmaz A, Oter S, Sadir S, Coskun O, Topal T, Ozler M, Bilgic H. Peroxynitrite may be involved in bladder damage caused by cyclophosphamide in rats. J Urol. 2005; 173(5): 1793-6.
19. Oter S, Korkmaz A, Topal T, Ozcan O, Sadir S, Ozler M, Ogur R, Bilgic H. Correlation between hyperbaric oxygen exposure pressures and oxidative parameters in rat lung, brain, and erythrocytes. Clin Biochem. 2005; 38(8): 706-11.
20. Farber JL, Kyle ME, Coleman JB. Mechanism of cell injury by activated oxygen species. Lab Invest. 1990; 62: 670-679.
21. Jannsen YMW, Van Houten B, Borm PJA, Mossman BT. Cell and tissue response to oxidative damage. Lab Invest. 1993; 69: 261-274.
22. Wiseman H, Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J. 1996; 313: 17-29.
23. Young IS, Woodside JV. Antioxidants in health and disease. J Clin Pathol. 2001; 54: 176-186.
24. Powis G, Briehl M, Oblong J. Redox signaling and the control of cell growth and death. Pharmacol Ther. 1995; 65: 149-173.
25. Lander HM. An essential role for free radicals and derived species in signal transduction. FASEB J. 1997; 11: 118-124.
26. Thannıckal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol. 2000; 279(6): L1005–L1028.
27. Bocci V, Valacchi G, Corradeschi F, Fanetti G. Studies on the biological effects of ozone: 8. Effects on the total antioxidant status and on interleukin-8 production. Mediat Inflamm. 1998; 7: 313-317.
28. Travagli V, Zanardi I, Silvietti A, Bocci V. A physicochemical investigation on the effects of ozone on blood. Int J Biol Macromol. 2007; 41(5): 504-11.
29. Valacchi G, Bocci V. Studies on the biological effects of ozone: 10. Release of factors from ozonated human platelets. Mediators Inflamm. 1999; 8(4-5): 205-9.
30. Bocci V, Aldinucci C. Biochemical modifications induced in human blood by oxygenation-ozonation. J Biochem Mol Toxicol. 2006; 20(3): 133-8.
31. Bocci V. Is it true that ozone is always toxic? The end of a dogma. Toxicology and Applied Pharmacology. 2006; 216: 493-504.
32. Di Paolo N, Bocci V, Gaggiotti E. Ozone therapy. Int J Artif Organs. 2004; 27(3): 168-75.
33. Halliwell B, Clement MV, Long LH. Hydrogen peroxide in the human body. FEBS Lett. 2000; 486: 10-13.
34. Bocci V, Aldinucci C, Bianchi L. The use of hydrogen peroxide as a medical drug. Riv Ital Ossigeno Ozonoterapia. 2005; 4: 30-39.
35. Rice-Evans C, Miller NJ. Total antioxidant status in plasma and body fluids. Methods Enzymol. 1994; 234: 279-93.
36. Bocci V, Aldinucci C, Mosci F, Carraro F, Valacchi G. Ozonation of human blood induces a remarkable upregulation of heme oxygenase-1 and heat stress protein-70. Mediators Inflamm. 2007; 2007: 1-6.
37. Fritz HB. Heme oxygenase-1: a therapeutic amplification funnel. FASEB J. 2005; 19(10): 1216-9.
38. LE Otterbein, MP Soares, K Yamashita, FH Bach. Heme oxygenase-1: unleashing the protective properties of heme. trends in Immunology. 2003; 24(8): 449-55.
39. Stübinger S, Sader R, Filippi A. The use of ozone in dentistry and maxillofacial surgery: a review. Quintessence Int. 2006; 37(5): 353-9.
40. Nogales CG, Ferrari PH, Kantorovich EO, Lage-Marques JL. Ozone therapy in medicine and dentistry. J Contemp Dent Pract. 2008; 9(4): 75-84.
41. Bocci V. The case for oxygen-ozonetherapy. Br J Biomed Sci. 2007; 64(1): 44-9.
42. Martínez-Sánchez G, Al-Dalain SM, Menéndez S, Re L, Giuliani A, Candelario-Jalil E, Alvarez H, Fernández-Montequín JI, León OS. Therapeutic efficacy of ozone in patients with diabetic foot. Eur J Pharmacol. 2005; 523(1-3): 151-61.
43. Muto M, Ambrosanio G, Guarnieri G, Capobianco E, Piccolo G, Annunziata G, Rotondo A. Low back pain and sciatica: treatment with intradiscal-intraforaminal O2-O3 injection. Our experience. Radiol med. 2008; 113: 695-706.
44. Bocci V. Ozone a new medical drug. Dordrecht. The Netherlands. Springer, 2005, p. 75-85.
45. Oter S, Korkmaz A. Relevance of hyperbaric oxygen to ozone therapy. Arch Med Res. 2006; 37(7): 917-8.
46. Guven A, Gundogdu G, Sadir S et al. The efficacy of ozone therapy in experimental caustic esophageal burn. J Pediatr Surg. 2008; 43(9): 1679-84.
47. Guven A, Gundogdu G, Sadir S, Topal T, Erdogan E, Korkmaz A et al. Medical ozone therapy reduces oxidative stress and ıntestinal damage in an experimental model of necrotizing enterocolitis in neonatal rats. J Pediatr Surg. 2009; in press.
48. Özler M, Ersöz N, Özerhan İH, Harlak A, Sadır S, Topal T, Öter Ş, Korkmaz A. Sıçanlarda oluşturulmuş peritoneal adezyon üzerine ozon tedavisinin etkisi. 2009; in press.