Skip to main content

Advertisement

SpringerLink
Log in

Anti-inflammatory Effect of Ozone Therapy in an Experimental Model of Rheumatoid Arthritis

  • Original Article
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

To verify the influence of ozone (O3) therapy on an experimental model of rheumatoid arthritis (RA), 30 male Wistar rats were randomly allocated to 2 groups, control (C) and treatment (T), and subdivided into control (C12, C48, C72) and treatment (T12, T48, T72) groups. RA was induced by administration of collagenase plus complete Freud’s adjuvant in the knee joint region. The animals were treated with ozone therapy (1 ml O3 injection in the knee i.a.) according to group assignment: T12, 2 h; T48, 2 and 24 h; and T72, 2, 24, and 48 h post-RA induction. The different animal groups were euthanized 12, 24, or 72 h post-RA induction, respectively. Synovial exudate levels of IL-10, IL-12p70, TNF-α, INF-γ, and MCP-1 were assessed by flow cytometry, and histopathological analysis of the knee cartilage was conducted. Ozone therapy effectively decreases inflammation, reducing IL-12 and TNF-α, and increasing IL10. O3 did not statistically affect INF-γ or MCP-1 levels. More expressive results were obtained with group T72, i.e., treated 2, 24, and 48 h post-RA induction, which indicates that longer-term ozone treatment is more effective than a single acute application. Ozone therapy effectively reduced inflammation with effects, at least in part, mediated through reduction of pro-inflammatory cytokines and activation of IL-10 anti-inflammatory cytokine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Tedgui, A., and Z. Mallat. 2001. Anti-inflammatory mechanisms in the vascular wall. Circulation Research 88: 877–887. https://doi.org/10.1161/hh0901.090440.

    Article  CAS  PubMed  Google Scholar 

  2. Ham, S., J.B. Bae, S. Lee, B.J. Kim, B.G. Han, S.K. Kwok, and T. Young Roh. 2019. Epigenetic analysis in rheumatoid arthritis synoviocytes. In Experimental and Molecular Medicine 51, vol. 51, 1–13. Springer: US. https://doi.org/10.1038/s12276-019-0215-5.

    Chapter  Google Scholar 

  3. Kapoor, T., and J. Bathon. 2018. Renal manifestations of rheumatoid arthritis. Rheumatic Disease Clinics of North America 44. Elsevier Inc: 571–584. https://doi.org/10.1016/j.rdc.2018.06.008.

    Article  PubMed  Google Scholar 

  4. Chin, C.Y., S.Y. Hsieh, and V.S. Tseng. 2018. EDram: effective early disease risk assessment with matrix factorization on a large-scale medical database: a case study on rheumatoid arthritis. PLoS One 13: 1–19. https://doi.org/10.1371/journal.pone.0207579.

    Article  CAS  Google Scholar 

  5. Hammer, Hilde, B. Berner, S. Michelsen, A. Provan, J. Sexton, J. Lampa, T. Uhlig, and T.K. Kvien. 2018. Tender joint count may not reflect inflammatory activity in established rheumatoid arthritis patients - results from a longitudinal study. Arthritis Care and Research. https://doi.org/10.1002/acr.23815.

  6. León, Fernández, O. Sonia, R. Viebahn-Haensler, G.L. Cabreja, I.S. Espinosa, Y.H. Matos, L.D. Roche, B.T. Santos, G.T. Oru, and J.C.P. Vega. 2016. Medical ozone increases methotrexate clinical response and improves cellular redox balance in patients with rheumatoid arthritis. European Journal of Pharmacology 789. Elsevier: 313–318. https://doi.org/10.1016/j.ejphar.2016.07.031.

    Article  CAS  Google Scholar 

  7. Vaillant, Jaqueline, Dranguet, A. Fraga, M.T. Díaz, A. Mallok, R. Viebahn-Hänsler, Z. Fahmy, A. Barberá, L. Delgado, S. Menéndez, and O.S.L. Fernández. 2013. Ozone oxidative postconditioning ameliorates joint damage and decreases pro-inflammatory cytokine levels and oxidative stress in PG/PS-induced arthritis in rats. European Journal of Pharmacology 714. Elsevier: 318–324. https://doi.org/10.1016/j.ejphar.2013.07.034.

    Article  CAS  PubMed  Google Scholar 

  8. Hammond, Alison. 2004. Rehabilitation in rheumatoid arthritis: a critical review. Musculoskeletal Care 2: 135–151. https://doi.org/10.1002/msc.66.

    Article  PubMed  Google Scholar 

  9. Katz, Jeffrey. 2006. Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. Journal of Bone and Joint Surgery - Series A 88: 21–24. https://doi.org/10.2106/JBJS.E.01273.

    Article  Google Scholar 

  10. Kallewaard, J.W., M. Terheggen, G.J. Groen, M.E. Sluijter, R. Derby, L. Kapural, N. Mekhail, and M. van Kleef. 2010. Evidence-based interventional pain medicine. 15. Discogenic low back pain. Pain Practice 10: 560–579. https://doi.org/10.1111/j.1533-2500.2010.00408.x.

    Article  PubMed  Google Scholar 

  11. Pereira, Marcelo Monteiro Sad, A. Navarini, L.M.J. Mimica, A.M. Pacheco Jr., and R.A. Silva. 2005. Efeito de diferentes gases sobre o crescimento bacteriano: estudo experimental “in vitro”. Revista do Colégio Brasileiro de Cirurgiões 32: 12–14. https://doi.org/10.1590/s0100-69912005000100004.

    Article  Google Scholar 

  12. Tirelli, U., C. Cirrito, M. Pavanello, C. Piasentin, A. Lleshi, and R. Taibi. 2019. Ozone therapy in 65 patients with fibromyalgia: an effective therapy. European Review for Medical and Pharmacological Sciences 23: 1786–1788. https://doi.org/10.26355/eurrev_201902_17141.

    Article  CAS  PubMed  Google Scholar 

  13. Smith, Noel, A. Wilson, J. Gandhi, S. Vatsia, and S. Khan. 2017. Ozone therapy: an overview of pharmacodynamics, current research, and clinical utility. Medical Gas Research 7: 212–219. https://doi.org/10.4103/2045-9912.215752.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Felder-Puig, Rosemarie, M. Gyimesi, T. Mittermayr, and S. Geiger-Gritsch. 2009. Chemonukleolyse und intradiskale Elektrotherapie: Was Ist die gegenwärtige Evidenz? RoFo Fortschritte auf dem Gebiet der Rontgenstrahlen und der Bildgebenden Verfahren 181: 936–944. https://doi.org/10.1055/s-0028-1109573.

    Article  CAS  Google Scholar 

  15. Di Mauro, Rosaria, G. Cantarella, R. Bernardini, M. Di Rosa, I. Barbagallo, A. Distefano, L. Longhitano, et al. 2019. The biochemical and pharmacological properties of ozone: the smell of protection in acute and chronic diseases. International Journal of Molecular Sciences 20. https://doi.org/10.3390/ijms20030634.

  16. Manoto, Sello, M.J. Maepa Lebohang, and S.K. Motaung. 2018. Medical ozone therapy as a potential treatment modality for regeneration of damaged articular cartilage in osteoarthritis. Saudi Journal of Biological Sciences 25. King Saud University: 672–679. https://doi.org/10.1016/j.sjbs.2016.02.002.

    Article  CAS  PubMed  Google Scholar 

  17. Braidy, Nady, Izadi Morteza, A. Sureda, N. Jonaidi-Jafari, A. Banki, S.F. Nabavi, and M.N. Seyed. 2018. Therapeutic relevance of ozone therapy in degenerative diseases: focus on diabetes and spinal pain. Journal of Cellular Physiology 233: 2705–2714. https://doi.org/10.1002/jcp.26044.

    Article  CAS  PubMed  Google Scholar 

  18. Marcelo, Freire, and T.E.V. Dyke. 2013. Natural resolution of inflammation. Periodontology 2000 (63): 149–164.

    Google Scholar 

  19. Aisha, Siddiqah, J. Ahmed, H. Li, A. Stark Erlandsson-Harris, and G.B.M. Ahmede. 2012. Suppression of pain and joint destruction by inhibition of the proteasome system in experimental osteoarthritis. Pain 153 (1): 18–26.

    Article  Google Scholar 

  20. Combe, R., S. Bramwell, and M.J. Field. 2004. The monosodium iodoacetate model of osteoarthritis: a model of chronic nociceptive pain in rats? Neuroscience Letters 370 (2–3): 236–240.

    Article  CAS  Google Scholar 

  21. Bove, S.E., S.L. Calcaterra, R.M. Brooker, C.M. Huber, R.E. Guzman, P.L. Juneau, D.J. Schrier, and K.S. Kilgore. 2003. Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis. Osteoarthritis and Cartilage 11 (11): 821–830.

    Article  CAS  Google Scholar 

  22. Pitcher, T., J. Sousa-Valente, and M. Malcangio. 2016. The monoiodoacetate model of osteoarthritis pain in the mouse. Journal of Visualized Experiments 111: e53746. https://doi.org/10.3791/53746.

    Article  Google Scholar 

  23. Chen, Huiqiang, B. Yu, C. Lu, and Q. Lin. 2013. The effect of intra-articular injection of different concentrations of ozone on the level of TNF-α, TNF-R1, and TNF-R2 in rats with rheumatoid arthritis. Rheumatology International 33: 1223–1227. https://doi.org/10.1007/s00296-012-2529-7.

    Article  CAS  PubMed  Google Scholar 

  24. Liou, Lieh Bang, W.P. Tsai, C.J. Chang, W. Ju Chao, and M. Hsin Chen. 2013. Blood monocyte chemotactic protein-1 (MCP-1) and adapted disease activity Score28-MCP-1: favorable indicators for rheumatoid arthritis activity. PLoS One 8: 1–9. https://doi.org/10.1371/journal.pone.0055346.

    Article  CAS  Google Scholar 

  25. Rajaiah, Rajesh, M. Puttabyatappa, S.K. Polumuri, and K.D. Moudgil. 2011. Interleukin-27 and interferon-γ are involved in regulation of autoimmune arthritis. Journal of Biological Chemistry 286: 2817–2825. https://doi.org/10.1074/jbc.M110.187013.

    Article  CAS  PubMed  Google Scholar 

  26. Trinchieri, Giorgio. 2003. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nature Reviews Immunology 3: 133–146. https://doi.org/10.1038/nri1001.

    Article  CAS  PubMed  Google Scholar 

  27. Noori-Zadeh, Ali, S. Bakhtiyari, R. Khooz, K. Haghani, and S. Darabi. 2019. Intra-articular ozone therapy efficiently attenuates pain in knee osteoarthritic subjects: a systematic review and meta-analysis. Complementary Therapies in Medicine 42. Elsevier: 240–247. https://doi.org/10.1016/j.ctim.2018.11.023.

    Article  PubMed  Google Scholar 

  28. Arias-Vázquez, Pedro Iván, C.A. Tovilla-Zárate, Y. Hernández-Díaz, T.B. González-Castro, I.E. Juárez-Rojop, M.L. López-Narváez, D.Y. Bermudez-Ocaña, H.A. Barjau-Madrígal, and G. Legorreta-Ramírez. 2019. Short-term therapeutic effects of ozone in the management of pain in knee osteoarthritis: a meta-analysis. PM & R : The Journal of Injury, Function, and Rehabilitation. https://doi.org/10.1002/pmrj.12088.

Download references

Author information

Authors and Affiliations

  1. Laboratory of Neuroanatomy and Neurophysiology, State University of the Central West of Paraná-Unicentro, Guarapuava, Brazil

    Ana Paula Santos Tartari, Felipe Figueiredo Moreira, Mário César Da Silva Pereira & Ivo Ilvan Kerppers

  2. Laboratory of Virology and Molecular Biology, State University of the Central West of Paraná-Unicentro, Guarapuava, Brazil

    Emerson Carraro

  3. Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil

    Francisco José Cidral-Filho & Afonso Inoue Salgado

  4. Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil

    Francisco José Cidral-Filho & Afonso Inoue Salgado

  5. Guarapuava, Brazil

    Ivo Ilvan Kerppers

Authors
  1. Ana Paula Santos Tartari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Felipe Figueiredo Moreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mário César Da Silva Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Emerson Carraro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francisco José Cidral-Filho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Afonso Inoue Salgado
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ivo Ilvan Kerppers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ivo Ilvan Kerppers.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights

All procedures performed in animal studies were in accordance with the ethical standards of the institution or practice in which the studies were conducted. Ethics committee in research, CEUA, 037/2016.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tartari, A.P.S., Moreira, F.F., Pereira, M.C.D.S. et al. Anti-inflammatory Effect of Ozone Therapy in an Experimental Model of Rheumatoid Arthritis. Inflammation 43, 985–993 (2020). https://doi.org/10.1007/s10753-020-01184-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-020-01184-2

KEY WORDS

Search

Navigation