Araştırma Makalesi
Effects of Different Ozone Doses Added to the Antibiotic Treatment on Cytokine Levels in Experimental Sepsis Model
Öz
We aimed to examine the changes caused by ozone therapy added to the antibiotic treatment on proinflammatory and anti-inflammatory cytokine levels in an experimental sepsis model formed with E. coli endotoxin. Rats were divided into 6 groups of 10 rats. Sepsis was formed by dosing 5 groups of rats with intraperitoneal E. coli endotoxin injection. For the first 3 groups, 0.6 mg/kg, 0.9 mg/kg, and 1.1 mg/kg doses of ozone therapy were added to the antibiotic treatment and group-4 only received antibiotic treatment. Group-5 was not treated. Group-6 received intraperitoneal serum physiologic injection simultaneously with the other groups. All treatments were sustained for 5 days. IL-1, IL-10, and TNF-alpha levels were detected in blood serum taken from rats sacrificed on day 6. It was seen that IL-1, TNF-alpha levels are significantly lower than the levels in other groups that received ozone therapy. In the comparisons amongst the groups receiving ozone therapy, it was observed that IL-1 levels do not have a significant difference and TNF-alpha levels are significantly lower in the two groups receiving lower doses than the group receiving a higher dose. There were no significant differences detected between groups at serum levels of IL-10 which is an anti-inflammatory cytokine. It was concluded that ozone added to the antibiotic treatment in sepsis could have a positive effect on survival rates by suppressing inflammatory process.
Kaynakça
- 1. Matot I, Srung CL. Definition of sepsis. Intensive Care Med. 2001;27:3-9.
- 2. Charalambos AG, Eugenia D, Harry PB, et al. Pro-versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapetic options. J Infect Dis. 2000;181:176-80.
- 3. Braithwaite SS. Prokalcitonin: New insights on regulation and origin. Crit Care Med. 2000;28:586-8.
- 4. Members of the American College of Chest Physician/Society of Critical Care Medicine consensus conference committee: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864–73.
- 5. Wintroub BU: Inflammation and mediators. Int J Dermatol. 1980;19:436–42.
- 6. Tracey KJ, Beutler B, Lowry SF, et al. Shock and tissue injury induced by recombinant human cachectin. Science. 1986;234:470–74.
- 7. Wakabayashi G, Gelfard JA, Jung WK, et al. Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock like state and tissue injury in rabbits without endotoxemia: Comparison to Escherichia coli. J Clin Invest. 1991;87:1925–35.
- 8. Marty C, Misset B, Tamion F, et al. Circulating interleukin-8 concentrations in patients with multiple organ failure of septic and nonseptic origin. Crit Care Med. 1994;22:673–9.
- 9. Damas P, Reuter A, Gysen P, et al. Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans. Crit Care Med. 1989;17:975–8.
- 10. Natanson C, Eichenholz PW, Danner RL, et al. Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J Exp Med. 1989;169:823–32.
- 11. International_Scientific_Committee of Ozone_Therapy: Madrid Declaration on Ozone Therapy. Erişim tarihi 10.11.2021, https://isco3.org/producto/madrid-declaration-on-ozone-therapy-3rd-edition-online-access-english/
- 12. Oter S, Edremitlioglu M, Korkmaz A, et al. Effects of hyperbaric oxygen treatment on liver functions, oxidative status and histology in septic rats. Intensive Care Med. 2005;31:1262-8.
- 13. Moraes MM, Coelho MS, Nascimento WM, et al. The antimicrobial effect of different ozone protocols applied in severe curved canals contaminated with Enterococcus faecalis: ex vivo study. Odontology. 2021;109(3):696-700.
- 14. To T, Zhang K, Maguire B, et al. UV, ozone, and COVID-19 transmission in Ontario, Canada using generalised linear models. Environ Res. 2021;194:110645.
- 15. Dyas A, Boughton BJ, Das BC. Ozone killing action against bacterial and fungal species: microbiological testing of a domestic ozone generator. J Clin Pathol.1983;36:1102-04.
- 16. Silva EJNL, Prado MC, Soares DN, et al. The effect of ozone therapy in root canal disinfection: a systematic review. Int Endod J. 2020;53(3):317-32.
- 17. Traore MB, Sun A, Gan Z, et al. Antimicrobial capacity of ultrasound and ozone for enhancing bacterial safety on inoculated shredded green cabbage (Brassica oleracea var. capitata). Can J Microbiol. 2020;66(2):125-37.
- 18. Sechi LA, Lezcano I, Nunez N, et al. Antibacterial activity of ozonized sunflower oil (oleozon). J Appl Microbiol. 2001;90:279-84.
- 19. Fan L, Song J, McRae KB, et al. Gaseous ozone therapy inactivates Listeria innocua in vitro. J Appl Microbio. 2007;103:2657-63.
- 20. Canning BJ, Hmieleski RR, Spannhake EW, et al. Ozone reduces murine alveolar and peritoneal macrophage phagocytosis: the role of prostanoids. Am J Physiol. 1991;261:277-82.
- 21. Chatterjee D, Mukherjee SK. Destruction of phagocytosis-supressing activity of aflatoxin B1 by ozone. Lett Appl Microbiol. 1993;17:52-4. 22. Canning BJ, Hmieleski RR, Spannhake EW, et al. Ozone reduces murine alveolar and peritoneal macrophage phagocytosis: the role of prostanoids. Am J Physiol. 1991;261(4):277–82.
- 23. Peralta C, Closa D, Xaus C, et al. Hepatic preconditioning in rats is defined by a balance of adenosine and xanthine. Hepatology. 1998;28(3):768–73.
- 24. Peralta C, Xaus C, Bartrons R, et al. Effect of ozone therapy on reactive oxygen species and adenosine production during hepatic ischemia-reperfusion. Free Radic Res. 2000;33(5):595–605.
- 25. Klosterhalfen B, Bhardwaj RS. Septic shock. Gen Pharmacol. 1998;31(1):25–32.
- 26. Zamora ZB, Borrego A, López OY, et al. Effects of ozone oxidative preconditioning on tnf-α release and antioxidant-prooxidant intracellular balance in mice during endotoxic shock, mediators of inflammation. 2005;1:16–22.
- 27. Victor VM, De la Fuente M. Several functions of immune cells in mice changed by oxidative stres caused by endotoxin. Physiol Res. 2003;52(6):789-96.
- 28. Bette M, Nuesing RM, Mutters R, et al. Efficiency of tazobactam/piperacilin in lethal peritonitis is enhanced after preconditioning of rats with O3/O2 pneumoperitoneum. Shock. 2006;1:26-9.
- 29. Schulz S, Rodriguez ZZ, Mutters R, et al. Repetitive pneumoperitoneum with ozonized oxygen as a preventive in lethal polymicrobial sepsis in rats. Eur Surg Res. 2003;35:26-34.
- 30. Rodríguez ZZ, Guanche A, Álvarez RG, et al. Preconditioning with ozone/oxygen mixture induces reversion of some indicators of oxidative stress and prevents organic damage in rats with fecal peritonitis. Inflamm Res. 2009;58:371-5.
- 31. Torossian A, Ruehlmann S, Eberhart L, et al. Pre-treatment with ozonized oxygen (O3) aggravates inflammation in septic rats. Inflamm Res. 2004;53:122-5.
- 32. Seghaye MC, Duchateau J, Bruniaux J, et al. Interleukin-10 release related to cardiopulmonary bypass in infants undergoing cardiac operations. J Thorac Cardiovasc Surg. 1996;111:545-53.
- 33. Kapicibaşi HO, Kiraz HA, Demir ET, et al. Pulmonary effects of ozone therapy at different doses combined with antibioticotherapy in experimental sepsis model. Acta Cir Bras. 2020;35(6):e202000604.
- 34. Kato T, Murata A, Ishida H, et al. Interleukin 10 reduces mortality from severe peritonitis in mice. Antimicrob Agents Chemother. 1995;39:1336-40.
- 35. Van der Poll T, Marchant A, Buurman WA, et al. Endogenous IL-10 protects mice from death during septic peritonitis. J Immunol. 1995;155:5397-401.
- 36. Sewnath ME, Olszyna DP, Birjmohun R, et al. IL-10-deficient mice demonstrate multiple organ failure and increased mortality during Escherichia coli peritonitis despite an accelerated bacterial clearance. J Immunol. 2001;166:6323-31.
Deneysel Sepsis Modelinde Antibiyotik Tedavisine Eklenen Farklı Dozlardaki Ozonun Sitokin Düzeylerine Etkisi
Öz
Bu çalışmada E.coli endotoksini ile oluşturulan deneysel sepsis modelinde antibiyotik tedavisine eklenen ozon tedavisinin proinflamatuvar ve antiinflamatuvar sitokin düzeylerinde yaptığı değişiklikleri incelemeyi amaçladık. Her birinde 10 rat olan 6 deney grubunun 5 tanesinde intraperitoneal E.coli endotoksini injeksiyonuyla sepsis oluşturuldu. İlk 3 grupta antibiyotik tedavisine 0.6 mg/kg, 0.9 mg/kg ve 1.1 mg/kg dozlarında ozon tedavisi eklenirken, 4. gruba sadece antibiyotik tedavisi verildi. 5. gruba tedavi verilmedi. 6. gruba ise diğer gruplarla eş zamanlı olarak intraperitoneal serum fizyolojik enjeksiyonu yapıldı. Tüm tedavilere 5 gün boyunca devam edildi. 6. günde sakrifiye edilen ratlardan alınan kanların serumlarında IL-1, IL-10 ve TNF-alfa düzeylerini çalışıldı. Ozon tedavisi verilen tüm gruplardaki proinflamatuvar sitokin düzeylerinin (IL-1, TNF-alfa) diğer gruplara göre anlamlı olarak düşük olduğunu tespit edildi. Ozon tedavisi verilen grupların kendi aralarında yapılan karşılaştırmada, IL-1 düzeylerinde anlamlı bir fark olmadığı, TNF-alfa düzeylerinin ise daha düşük doz verilen iki grupta (0.6 mg/kg ve 0.9 mg/kg) yüksek doz verilen gruba (1.1 mg/kg) göre anlamlı olarak düşük olduğu gözlemlendi. Antiinflamatuvar bir sitokin olan IL-10’un serum düzeylerinde ise gruplar arasında anlamlı bir farklılık tespit edilmedi. Sonuç olarak, sepsiste antibiyotik tedavisine eklenen ozon tedavisinin inflamatuar süreci baskılayarak sağ kalım oranlarına olumlu etki yapabileceği sonucuna varıldı.
Kaynakça
- 1. Matot I, Srung CL. Definition of sepsis. Intensive Care Med. 2001;27:3-9.
- 2. Charalambos AG, Eugenia D, Harry PB, et al. Pro-versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapetic options. J Infect Dis. 2000;181:176-80.
- 3. Braithwaite SS. Prokalcitonin: New insights on regulation and origin. Crit Care Med. 2000;28:586-8.
- 4. Members of the American College of Chest Physician/Society of Critical Care Medicine consensus conference committee: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864–73.
- 5. Wintroub BU: Inflammation and mediators. Int J Dermatol. 1980;19:436–42.
- 6. Tracey KJ, Beutler B, Lowry SF, et al. Shock and tissue injury induced by recombinant human cachectin. Science. 1986;234:470–74.
- 7. Wakabayashi G, Gelfard JA, Jung WK, et al. Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock like state and tissue injury in rabbits without endotoxemia: Comparison to Escherichia coli. J Clin Invest. 1991;87:1925–35.
- 8. Marty C, Misset B, Tamion F, et al. Circulating interleukin-8 concentrations in patients with multiple organ failure of septic and nonseptic origin. Crit Care Med. 1994;22:673–9.
- 9. Damas P, Reuter A, Gysen P, et al. Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans. Crit Care Med. 1989;17:975–8.
- 10. Natanson C, Eichenholz PW, Danner RL, et al. Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J Exp Med. 1989;169:823–32.
- 11. International_Scientific_Committee of Ozone_Therapy: Madrid Declaration on Ozone Therapy. Erişim tarihi 10.11.2021, https://isco3.org/producto/madrid-declaration-on-ozone-therapy-3rd-edition-online-access-english/
- 12. Oter S, Edremitlioglu M, Korkmaz A, et al. Effects of hyperbaric oxygen treatment on liver functions, oxidative status and histology in septic rats. Intensive Care Med. 2005;31:1262-8.
- 13. Moraes MM, Coelho MS, Nascimento WM, et al. The antimicrobial effect of different ozone protocols applied in severe curved canals contaminated with Enterococcus faecalis: ex vivo study. Odontology. 2021;109(3):696-700.
- 14. To T, Zhang K, Maguire B, et al. UV, ozone, and COVID-19 transmission in Ontario, Canada using generalised linear models. Environ Res. 2021;194:110645.
- 15. Dyas A, Boughton BJ, Das BC. Ozone killing action against bacterial and fungal species: microbiological testing of a domestic ozone generator. J Clin Pathol.1983;36:1102-04.
- 16. Silva EJNL, Prado MC, Soares DN, et al. The effect of ozone therapy in root canal disinfection: a systematic review. Int Endod J. 2020;53(3):317-32.
- 17. Traore MB, Sun A, Gan Z, et al. Antimicrobial capacity of ultrasound and ozone for enhancing bacterial safety on inoculated shredded green cabbage (Brassica oleracea var. capitata). Can J Microbiol. 2020;66(2):125-37.
- 18. Sechi LA, Lezcano I, Nunez N, et al. Antibacterial activity of ozonized sunflower oil (oleozon). J Appl Microbiol. 2001;90:279-84.
- 19. Fan L, Song J, McRae KB, et al. Gaseous ozone therapy inactivates Listeria innocua in vitro. J Appl Microbio. 2007;103:2657-63.
- 20. Canning BJ, Hmieleski RR, Spannhake EW, et al. Ozone reduces murine alveolar and peritoneal macrophage phagocytosis: the role of prostanoids. Am J Physiol. 1991;261:277-82.
- 21. Chatterjee D, Mukherjee SK. Destruction of phagocytosis-supressing activity of aflatoxin B1 by ozone. Lett Appl Microbiol. 1993;17:52-4. 22. Canning BJ, Hmieleski RR, Spannhake EW, et al. Ozone reduces murine alveolar and peritoneal macrophage phagocytosis: the role of prostanoids. Am J Physiol. 1991;261(4):277–82.
- 23. Peralta C, Closa D, Xaus C, et al. Hepatic preconditioning in rats is defined by a balance of adenosine and xanthine. Hepatology. 1998;28(3):768–73.
- 24. Peralta C, Xaus C, Bartrons R, et al. Effect of ozone therapy on reactive oxygen species and adenosine production during hepatic ischemia-reperfusion. Free Radic Res. 2000;33(5):595–605.
- 25. Klosterhalfen B, Bhardwaj RS. Septic shock. Gen Pharmacol. 1998;31(1):25–32.
- 26. Zamora ZB, Borrego A, López OY, et al. Effects of ozone oxidative preconditioning on tnf-α release and antioxidant-prooxidant intracellular balance in mice during endotoxic shock, mediators of inflammation. 2005;1:16–22.
- 27. Victor VM, De la Fuente M. Several functions of immune cells in mice changed by oxidative stres caused by endotoxin. Physiol Res. 2003;52(6):789-96.
- 28. Bette M, Nuesing RM, Mutters R, et al. Efficiency of tazobactam/piperacilin in lethal peritonitis is enhanced after preconditioning of rats with O3/O2 pneumoperitoneum. Shock. 2006;1:26-9.
- 29. Schulz S, Rodriguez ZZ, Mutters R, et al. Repetitive pneumoperitoneum with ozonized oxygen as a preventive in lethal polymicrobial sepsis in rats. Eur Surg Res. 2003;35:26-34.
- 30. Rodríguez ZZ, Guanche A, Álvarez RG, et al. Preconditioning with ozone/oxygen mixture induces reversion of some indicators of oxidative stress and prevents organic damage in rats with fecal peritonitis. Inflamm Res. 2009;58:371-5.
- 31. Torossian A, Ruehlmann S, Eberhart L, et al. Pre-treatment with ozonized oxygen (O3) aggravates inflammation in septic rats. Inflamm Res. 2004;53:122-5.
- 32. Seghaye MC, Duchateau J, Bruniaux J, et al. Interleukin-10 release related to cardiopulmonary bypass in infants undergoing cardiac operations. J Thorac Cardiovasc Surg. 1996;111:545-53.
- 33. Kapicibaşi HO, Kiraz HA, Demir ET, et al. Pulmonary effects of ozone therapy at different doses combined with antibioticotherapy in experimental sepsis model. Acta Cir Bras. 2020;35(6):e202000604.
- 34. Kato T, Murata A, Ishida H, et al. Interleukin 10 reduces mortality from severe peritonitis in mice. Antimicrob Agents Chemother. 1995;39:1336-40.
- 35. Van der Poll T, Marchant A, Buurman WA, et al. Endogenous IL-10 protects mice from death during septic peritonitis. J Immunol. 1995;155:5397-401.
- 36. Sewnath ME, Olszyna DP, Birjmohun R, et al. IL-10-deficient mice demonstrate multiple organ failure and increased mortality during Escherichia coli peritonitis despite an accelerated bacterial clearance. J Immunol. 2001;166:6323-31.
Toplam 35 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | İç Hastalıkları |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Yayımlanma Tarihi | 21 Ağustos 2023 |
| Gönderilme Tarihi | 5 Nisan 2022 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 10 Sayı: 2 |
