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The effects of systemic ozone application and hyperbaric oxygen therapy on knee osteoarthritis: an experimental study in rats

Abstract

Objective

To evaluate the effects of systemic medical ozone (O3) application and hyperbaric oxygen (HBO) therapy on surgically induced knee osteoarthritis (OA) in a rat model.

Materials and methods

We performed anterior cruciate ligament transection (ACLT) in order to create experimental OA in the right knees of 27 male rats. The left knee joints of all rats were sham-operated without ACLT as the negative control group. The rats were randomly assigned into three groups: (1) control group, which received no treatment; (2) O3 group, which received intraperitoneal 30 μg medical O3; (3) HBO group, which received HBO therapy for 60 minutes twice a day. We sacrificed the rats on the tenth week after the operation. We evaluated the degree of OA using Mankin scores.

Results

As a result of histopathological examination, the mean Mankin scores in the right knees with ACLT were 8.17 ± 2.12 in the control group, 6.22 ± 1.56 in the HBO group, and 4.72 ± 1.30 in the O3 group. The differences between the O3 group and the HBO group and the O3 group and the control group were found to be statistically significant (p 0.001, p 0.039, respectively). There was no difference between the HBO group and the control group (p 0.086).

Conclusions

The results of the present study show that systemic medical O3 application was more effective than HBO therapy and may reduce development of cartilage damage and prevent OA formation.

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References

  1. Buckwalter JA, Mankin HJ, Grodzinsky AJ (2005) Articular cartilage and osteoarthritis. Instr Course Lect 54:465

    PubMed  Google Scholar 

  2. Goldring M, Goldring S (2010) Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci 1192:230–237. https://doi.org/10.1111/j.1749-6632.2009.05240.x

    CAS  Article  PubMed  Google Scholar 

  3. Ashkavand Z, Malekinejad H, Vishwanath BS (2013) The pathophysiology of osteoarthritis. J Pharm Res 7(1):132–138

    CAS  Google Scholar 

  4. Goldring SR, Goldring MB (2004) The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res 427:S27–S36

    Article  Google Scholar 

  5. Manoto SL, Maepa MJ, Motaung SK (2018) Medical ozone therapy as a potential treatment modality for regeneration of damaged articular cartilage in osteoarthritis. Saudi J Biol Sci 25(4):672–679

    CAS  Article  Google Scholar 

  6. Bocci, V. (2002). Oxygen-ozone therapy: a critical evaluation. Springer Science & Business Media, Dordrecht

  7. Shallenberger F, HMD A (2011) Prolozone™–regenerating joints and eliminating pain. J Prolother 3(2):630–638

  8. Lindell K Weaver (2014). Hyperbaric oxygen therapy indications, thirteenth edn. The Hyperbaric Oxygen Therapy Committee Report. Best Publishing Company, Florida

  9. Yuan LJ, Ueng SW, Lin SS, Yeh WL, Yang CY, Lin PY (2004) Attenuation of apoptosis and enhancement of proteoglycan synthesis in rabbit cartilage defects by hyperbaric oxygen treatment are related to the suppression of nitric oxide production. J Orthop Res 22(5):1126–1134

    CAS  Article  Google Scholar 

  10. Ueng SW, Yuan LJ, Lin SS, Niu CC, Chan YS, Wang IC et al (2013) Hyperbaric oxygen treatment prevents nitric oxide-induced apoptosis in articular cartilage injury via enhancement of the expression of heat shock protein 70. J Orthop Res 31(3):376–384

    CAS  Article  Google Scholar 

  11. Nagatomo F, Gu N, Fujino H, Okiura T, Morimatsu F, Takeda I, Ishihara A (2010) Effects of exposure to hyperbaric oxygen on oxidative stress in rats with type II collagen-induced arthritis. Clin Exp Med 10(1):7–13

    CAS  Article  Google Scholar 

  12. Kuyinu EL, Narayanan G, Nair LS, Laurencin CT (2016) Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthop Surg Res 11(1). https://doi.org/10.1186/s13018-016-0346-5

  13. Hayami T, Pickarski M, Zhuo Y, Wesolowski GA, Rodan GA, Duong LT (2006) Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. Bone 38(2):234–243

    Article  Google Scholar 

  14. Williams JM, Felten DL, Peterson RG, O’Connor BL (1982) Effects of surgically induced instability on rat knee articular cartilage. J Anat 134(Pt 1):103

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Galois L, Etienne S, Grossin L, Cournil C, Pinzano A, Netter P et al (2003) Moderate-impact exercise is associated with decreased severity of experimental osteoarthritis in rats. Rheumatology 42(5):692–693

    CAS  Article  Google Scholar 

  16. Mankin HJ, Dorfman H, Lippiello L, Zarins A (1971) Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 53(3):523–537

    CAS  Article  Google Scholar 

  17. Yu B, Lin Q-R, Wang B-W, Zhu Q, He X-F (2010) Effect of intra-articular ozone injection on degenerative knee cartilage in rats.  Int J Ozone Ther 9:14–20

  18. Naito K, Watari T, Furuhata A, Yomogida S, Sakamoto K, Kurosawa H et al (2010) Evaluation of the effect of glucosamine on an experimental rat osteoarthritis model. Life Sci 86(13-14):538–543

    CAS  Article  Google Scholar 

  19. Jean YH, Wen ZH, Chang YC, Hsieh SP, Tang CC, Wang YH, Wong CS (2007) Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transected knee in rats: role of excitatory amino acids. Osteoarthr Cartil 15(6):638–645

    Article  Google Scholar 

  20. Paoloni M, Di Sante L, Cacchio A, Apuzzo D, Marotta S et al (2009) Intramuscular oxygen-ozone therapy in the treatment of acute back pain with lumbar disc herniation: a multicenter, randomized, double-blind, clinical trial of active and simulated lumbar paravertebral injection. Spine 4(13):1337–1344

    Article  Google Scholar 

  21. Bocci VA (2006) Scientific and medical aspects of ozone therapy. State of the art. Arch Med Res 37(4):425–435. https://doi.org/10.1016/j.arcmed.2005.08.006

    CAS  Article  PubMed  Google Scholar 

  22. Vaillant JD, Fraga A, Díaz MT, Mallok A, Viebahn-Hänsler R, Fahmy Z et al (2013) Ozone oxidative postconditioning ameliorates joint damage and decreases pro-inflammatory cytokine levels and oxidative stress in PG/PS-induced arthritis in rats. Eur J Pharmacol 714(1-3):318–324

    CAS  Article  Google Scholar 

  23. Zhao X, Li Y, Lin X, Wang J, Zhao X, Xie J, Sun T, Fu Z (2018) Ozone induces autophagy in rat chondrocytes stimulated with IL-1β through the AMPK/mTOR signaling pathway. J Pain Res 11:3003–3017. https://doi.org/10.2147/JPR.S183594

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Oladazimi S, Azarbayejani MA (2020) Evaluation of ALK5 and MMP13 expression in the cartilage tissue of rats with osteoarthritis rats and effects of exercise training, ozone and mesenchymal stem cell therapies on expression of these genes. Med. Lab. J. 14(1):50–56. https://doi.org/10.29252/mlj.14.1.50

  25. Chen H, Yu B, Lu C, Lin Q (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. Rheumatol Int 33(5):1223–1227. https://doi.org/10.1007/s00296-012-2529-7

    CAS  Article  PubMed  Google Scholar 

  26. Fernandez-Cuadros ME, Perez-Moro OS, Mirón-Canelo JA (2016) Could ozone be used as a feasible future treatment in osteoarthritis of the knee. Divers Equal Health Care 13(3):232–9

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Acknowledgments

We would like to acknowledge Fatma Nur Yürüm and Aslı Muratlı MD for their support in their pathological examination.

Funding

This work was supported by Çanakkale Onsekiz Mart University, The Scientific Research Coordination Unit, Project number: TTU-2019-3122.

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Correspondence to Onur Yılmaz.

Ethics declarations

All animal experiments were conducted in compliance with the “Guide for the Care and Use of Laboratory Animals” published by the US National Institutes of Health (revised, 1985).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

Ethical approval was given by the Çanakkale Onsekiz Mart University Animal Care and Ethics Committee for animal studies. Approval number: 2019/07-01

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Yılmaz, O., Bilge, A., Erken, H.Y. et al. The effects of systemic ozone application and hyperbaric oxygen therapy on knee osteoarthritis: an experimental study in rats. International Orthopaedics (SICOT) 45, 489–496 (2021). https://doi.org/10.1007/s00264-020-04871-9

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  • DOI: https://doi.org/10.1007/s00264-020-04871-9

Keywords

  • Hyperbaric Oxygen
  • Osteoarthritis
  • Ozone