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Beneficial Effects of Ozone Therapy on Oxidative Stress, Cardiac Functions and Clinical Findings in Patients with Heart Failure Reduced Ejection Fraction

Cardiovascular Toxicology volume 17, pages 426–433 (2017)Cite this article

Abstract

The aim of study was to determine the effects of ozone therapy on the oxidative stress, cardiac functions and clinical findings in patients with heart failure reduced ejection fraction (HFrEF). A total of 40 patients with New York Heart Association 2 and 3 HF with left ventricular ejection fraction (LVEF) <35%, and 40 subjects without HF as control group were included in the study. Patients with HFrEF were given additional ozone therapy of major and minor administrations along with conventional HF treatment for 5 weeks. Before and after ozone therapy, left ventricular end-systolic and end-diastolic volumes (LVESV, LVEDV) and the 6 minute walk distance (6MWD) and blood levels of the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSHPx), malondialdehyde (MDA), nitric oxide (NO) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. Ozone therapy significantly reduced the serum levels of NO and MDA (p < 0.001, respectively) and significantly increased the levels of SOD, CAT, GSH and GSHPx (p < 0.001, respectively). LVEDV and LVESV were found to be significantly reduced; however, LVEF was not found to be significantly increased (p = 0.567). As the biochemical improvement marker of HF, NT-proBNP was significantly reduced (p < 0.001). The clinical HF improvement marker of 6 minute walk distance was also modestly increased (p < 0.001). Ozone therapy might be beneficial in terms of activating antioxidant system and merit further therapeutic potential to conventional HF treatment in patients with HFrEF.

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References

  1. Sawyer, D. B. (2011). Oxidative stress in heart failure: what are we missing? The American Journal of the Medical Sciences, 342, 120–124.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Amir, O., Paz, H., Rogowski, O., Barshai, M., Sagiv, M., Shnizer, S., et al. (2009). Serum oxidative stress level correlates with clinical parameters in chronic systolic heart failure patients. Clinical Cardiology, 32, 199–203.

    Article  PubMed  Google Scholar 

  3. Nain, S., Wojnarowicz, C., Laarveld, B., & Olkowski, A. A. (2008). Effects of dietary vitamin E and C supplementation on heart failure in fast growing commercial broiler chickens. British Poultry Science, 49, 697–704.

    Article  CAS  PubMed  Google Scholar 

  4. Bocci, V. (2006). Scientific and medical aspects of ozone therapy state of the art. Archives of Medical Research, 37, 425–435.

    Article  CAS  PubMed  Google Scholar 

  5. Stübinger, S., Sader, R., & Filippi, A. (2006). The use of ozone in dentistry and maxillofacial surgery: a review. Quintessence International, 37, 353–359.

    PubMed  Google Scholar 

  6. Nogales, C. G., Ferrari, P. H., Kantorovich, E. O., & Lage-Marques, J. L. (2008). Ozone therapy in medicine and dentistry. The Journal of Contemporary Dental Practice, 9, 75–84.

    PubMed  Google Scholar 

  7. Martínez-Sánchez, G., Al-Dalain, S. M., Menéndez, S., Re, L., Giuliani, A., Candelario-Jalil, E., et al. (2005). Therapeutic efficacy of ozone in patients with diabetic foot. European Journal of Pharmacology, 523, 151–161.

    Article  PubMed  Google Scholar 

  8. Di Paolo, N., Gaggiotti, E., & Galli, F. (2005). Extracorporeal blood oxygenation and ozonation: clinical and biological implications of ozone therapy. Redox Report, 10, 121–130.

    Article  PubMed  Google Scholar 

  9. The International Scientific Committee of Ozone Therapy, “Madrid declaration on ozone therapy,” http://www.aepromo.org/declaracion madrid/Madrid declaration.pdf.

  10. Bocci, V., & Oxygen-ozone therapy. (2002). A critical evaluation (pp. 1–427). Dordrecht, The Netherlands: Kluwer Academic Publishers.

    Google Scholar 

  11. Bocci, V. A., Zanardi, I., & Travagli, V. (2011). Ozone acting on human blood yields a hormetic dose-response relationship. Journal of Translational Medicine, 17, 66.

    Article  Google Scholar 

  12. Bocci, V., Zanardi, I., Huijberts, M. S., & Travagli, V. (2011). Diabetes and chronic oxidative stress. A perspective based on the possible usefulness of ozone therapy. Diabetes and Metabolic Syndrome, 5(1), 45–49.

    Article  PubMed  Google Scholar 

  13. Placer, Z. A., Chusman, L., & Johnson, B. C. (1966). Estimation of products of lipid peroxidation in biological fluids. Analytical Biochemistry, 16, 359–364.

    Article  CAS  PubMed  Google Scholar 

  14. Lawrence, R. A., & Burk, R. F. (1976). Glutathione peroxidase activity in selenium-deficient rat liver. Biochemical and Biophysical Research Communications, 71, 952–958.

    Article  CAS  PubMed  Google Scholar 

  15. Sun, Y., Larry, W. O., & Ying, L. (1988). A simple method for clinical assay of superoxide dismutase. Clinical Chemistry, 34, 497–500.

    CAS  PubMed  Google Scholar 

  16. Sedlak, J., & Lindsay, R. H. C. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Analytical Biochemistry, 25, 192–205.

    Article  CAS  PubMed  Google Scholar 

  17. Aebi, H. E. (1987). Catalase. In H. U. Bergmeyer (Ed.), Methods of enzymatic analysis (3rd ed., pp. 273–286). Florida: Verlag Chemie, Weinheim.

    Google Scholar 

  18. Schiller, N. B., Shah, P. M., Crawford, M., DeMaria, A., Devereux, R., Feigenbaum, H., et al. (1989). Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two Dimensional Echocardiograms. Journal of the American Society of Echocardiography, 2, 358–367.

    Article  CAS  PubMed  Google Scholar 

  19. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. (2002). ATS statement: guidelines for the six-minute walk test. American Journal of Respiratory and Critical Care Medicine, 166, 111–117.

    Article  Google Scholar 

  20. Pimentel, D. R., Amin, J. K., Xiao, L., Miller, T., Viereck, J., Oliver-Krasinski, J., et al. (2001). Reactive oxygen species mediate amplitude-dependent hypertrophic and apoptotic responses to mechanical stretch in cardiac myocytes. Circulation Research, 89, 453–460.

    Article  CAS  PubMed  Google Scholar 

  21. Arstall, M. A., Sawyer, D. B., Fukazawa, R., & Kelly, R. A. (1999). Cytokine-mediated apoptosis in cardiac myocytes: the role of inducible nitric oxide synthase induction and peroxynitrite generation. Circulation Research, 85, 829–840.

    Article  CAS  PubMed  Google Scholar 

  22. Hill, M. F., & Singal, P. K. (1996). Antioxidant and oxidative stress changes during heart failure subsequent to myocardial infarction in rats. American Journal of Pathology, 148, 291–300.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Hill, M. F., & Singal, P. K. (1997). Right and left myocardial antioxidant responses during heart failure subsequent to myocardial infarction. Circulation, 96, 2414–2420.

    Article  CAS  PubMed  Google Scholar 

  24. Belch, J. J., Bridges, A. B., Scott, N., & Chopra, M. (1991). Oxygen free radicals and congestive heart failure. British Heart Journal, 65, 245–248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Arai, M., Alpert, N. R., MacLennan, D. H., Barton, P., & Periasamy, M. (1993). Alterations in sarcoplasmic reticulum gene expression in human heart failure. A possible mechanism for alterations in systolic and diastolic properties of the failing myocardium. Circulation Research, 72, 463–469.

    Article  CAS  PubMed  Google Scholar 

  26. Bocci, V. (1996). Does ozone therapy normalize the cellular redox balance? Implications for therapy of human immunodeficiency virus infection and several other diseases. Medical Hypotheses, 46(2), 150–154.

    Article  CAS  PubMed  Google Scholar 

  27. Borrego, A., Zamora, Z. B., González, R., Romay, C., Menéndez, S., Hernández, F., et al. (2004). Protection by ozone preconditioning is mediated by the antioxidant system in cisplatin-induced nephrotoxicity in rats. Mediators of Inflammation, 1, 13–19.

    Article  Google Scholar 

  28. Safwat, M. H., El-Sawalhi, M. M., Mausouf, M. N., & Shaheen, A. A. (2014). Ozone ameliorates age-related oxidative stress changes in rat liver and kidney: Effects of pre- and post-ageing administration. Biochemistry, 5, 450–458.

    Google Scholar 

  29. Borrelli, E., Diadori, A., Zalaffi, A., & Bocci, V. (2012). Effects of major ozonated autohemotherapy in the treatment of dry age related macular degeneration: a randomized controlled clinical study. International Journal of Ophthalmology, 5(6), 708–713.

    PubMed  PubMed Central  Google Scholar 

  30. Wu, X. N., Zhang, T., Wang, J., Liu, X. Y., Li, Z. S., Xiang, W., et al. (2016). Magnetic resonance diffusion tensor imaging following major ozonated autohemotherapy for treatment of acute cerebral infarction. Neural Regeneration Research, 11(7), 1115–1121.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ghatak, A., Brar, M. J., Agarwal, A., Goel, N., Rastogi, A. K., Vaish, A. K., et al. (1996). Oxy free radical system in heart failure and therapeutic role of oral vitamin E. International Journal of Cardiology, 57, 119–127.

    Article  CAS  PubMed  Google Scholar 

  32. Keith, M. E., Jeejeebhoy, K. N., Langer, A., Kurian, R., Barr, A., O’Kelly, B., et al. (2001). A controlled clinical trial of vitamin E supplementation in patients with congestive heart failure. The American Journal of Clinical Nutrition, 73, 219–224.

    CAS  PubMed  Google Scholar 

  33. Ishiyama, T., Morita, Y., Toyama, S., Yamagami, T., & Tsukamoto, N. (1976). A clinical study of the effect of coenzyme Q on congestive heart failure. Japanese Heart Journal, 17, 32–42.

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by the Scientific Research Fund of Erzincan University.

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Authors and Affiliations

  1. Department of Cardiology, Faculty of Medicine, Erzincan University, 24500, Erzincan, Turkey

    Mutlu Buyuklu, Eftal Murat Bakırcı, Husnu Degirmenci, Hikmet Hamur & Ergun Topal

  2. Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, 25000, Erzurum, Turkey

    Fatih Mehmet Kandemir & Sefa Kucukler

  3. Department of Family Physician, Faculty of Medicine, Karadeniz Technical University, 61000, Trabzon, Turkey

    Turan Set

  4. Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Necmettin Erbakan University, 42000, Konya, Turkey

    Kultigin Turkmen

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  1. Mutlu Buyuklu
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  2. Fatih Mehmet Kandemir
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Correspondence to Mutlu Buyuklu.

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Buyuklu, M., Kandemir, F.M., Set, T. et al. Beneficial Effects of Ozone Therapy on Oxidative Stress, Cardiac Functions and Clinical Findings in Patients with Heart Failure Reduced Ejection Fraction. Cardiovasc Toxicol 17, 426–433 (2017). https://doi.org/10.1007/s12012-017-9400-8

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