Research Article: Pulmonary effects of ozone therapy at different doses combined with antibioticotherapy in experimental sepsis model1

Date Published: July 13, 2020

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia

Author(s): Hasan Oğuz Kapicibaşi, Hasan Ali Kiraz, Emin Tunç Demir, Yasemen Adali, Sait Elmas.


This experimental sepsis model created with Escherichia coli aimed to investigate the histopathological effects of two different doses of ozone combined with antibiotherapy on lung tissue.

Rats were divided into 5 groups. Then sepsis was induced intraperitoneally in the first 4 groups. The 1st group was treated with cefepime, the 2nd and 3rd groups were treated with cefepime combined with ozone at a dose of 0.6 mg/kg and 1.1 mg/kg. Lung tissue sections were stained with hematoxylin-eosin and assessed under light microscope and scored between 0-4 in terms of histopathological findings.

In the comparisons between Group 1 and Group 4 in terms of cellular damage (p=0.030), inflammation (p=0.000) and overall score (p=0.007), statistically significant positive effects were observed in favor of Group 1. In the comparisons of Groups 2 and 3 with Group 4, only positive effects were observed in terms of inflammation (p=0.020, p=0.012, respectively).

Although negative histopathological effects of ozone on tissue injury were detected, it was noteworthy that the increase in the ozone dose reduced the number of damaged parameters.

Partial Text

Sepsis is defined as life-threatening organ dysfunction caused by an unregulated host response to infection1. The pathology of sepsis involves complex interactions between host organs and invading pathogens. Ultimately tissue injury and organ failure are due to negative effects of systemic activation of host immunity2,3. Sepsis forms a large problem in intensive care and is the main cause of death occurring there4,5. According to a report published by the Global Burden of Disease, each year nearly 10 million people die from infections and this is much greater than the number of people who die from cancer annually6. Lungs are the first organs affected by sepsis and sepsis causes severe injury to lung tissue7. In spite of advanced antibiotherapy, supportive treatments and all technological opportunities, sepsis continues to be a situation progressing with morbidity and mortality8. The earliest target-directed basic treatment principles for sepsis comprise determining high-risk patients, ensuring appropriate cultures and source control, and beginning appropriate antibiotherapy without delay9.

Ethical approval was obtained from Çanakkale Onsekiz Mart University Ethical Board of Animal Studies (File Registration Number: 2018/1800080971 & Decision number: 2018/06-06). Our study included 40 male Sprague-Dawley rats with mean weight 350-400 g in appropriate condition. During the study, rats were kept in ÇOMÜ Experimental Research Center in wire cages with 12-hour night-12-hour day circadian rhythm, environmental temperature 24-26°C and humidity 50-60%. Rats were fed with standard commercial feed and municipal drinking water. Rat feed was stopped 12 hours before the study; however, water was given freely during this time. All rat care was performed in accordance with the “Regulation on the Welfare and Protection of Animals Used for Experimental and Other Scientific Purposes” (13.12.2011-28141) prepared by the Ministry of Food, Agriculture and Livestock.

Sepsis-linked acute lung injury is an important cause of morbidity and mortality in adults and children and significantly contributes to intensive care costs17-20. Many studies have created pioneering ideas for the use of ozone as a strong antimicrobial agent21-24. Ozone is a strong oxidizing agent and important disinfectant. According to literature data, exposure of bacteria, spores and viruses to ozone for only a few minutes causes inactivation25-26. Studies by Ricevudi et al.27 proposed oxygen-ozone treatment as a new immunotherapeutic treatment method for the viral agent COVID-19 causing this pandemic and that patients with COVID-19 using this in combination with other treatment methods would benefit from the assisting and synergic effects of ozone therapy. Again, as stated by Ricevudi et al.27 the need for more studies is clear. The bactericidal effect of ozone is linked to attacking the biological material in microorganisms through the oxidation pathway. In fact, the antibacterial effect of ozone is said to be more effective than iodine and chlorine23,28. Previous experimental studies have shown that ozone therapy has experimental benefits on pathologic processes16,23,29. In many organs like pancreas, peritoneum, liver, mesenteric lymph nodes and cecum, ozone therapy has proven reducing effects on bacterial translocation16. In an experimental necrotizing pancreatitis model, ozone therapy was seen to be more effective to reduce oxidative stress levels, tissue injury and bacterial translocation rates compared to hyperbaric oxygen treatment30. Schulz et al.31 observed a decrease in polymicrobial peritonitis after they administered intraperitoneal ozone. Çakır et al.32 reported the systemic inflammatory response markers of TNF-alpha and IL-1B levels reduced after ozone treatment. An experimental sepsis study by Yamanel et al.16 compared hyperbaric oxygen treatment with ozone therapy and identified that both methods lowered oxidative stress indices, myeloperoxidase activity and serum proinflammatory cytokine levels. As a result, histopathologic injury reduced in the lung tissue of septic rats and ozone therapy showed to provide more benefits according to histopathologic injury scores and IL-1B levels. As a result of the experimental study, they proposed that ozone therapy may be a complementary medicine treatment method that could be applied together with antibiotherapy for sepsis.

Data obtained as a result of our study lead to the consideration that ozone therapy administered in addition to antibiotherapy may cause negative effects on lung tissue damaged due to sepsis.




Leave a Reply

Your email address will not be published.