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.
Similar content being viewed by others
References
Buckwalter JA, Mankin HJ, Grodzinsky AJ (2005) Articular cartilage and osteoarthritis. Instr Course Lect 54:465
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
Ashkavand Z, Malekinejad H, Vishwanath BS (2013) The pathophysiology of osteoarthritis. J Pharm Res 7(1):132–138
Goldring SR, Goldring MB (2004) The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res 427:S27–S36
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
Bocci, V. (2002). Oxygen-ozone therapy: a critical evaluation. Springer Science & Business Media, Dordrecht
Shallenberger F, HMD A (2011) Prolozone™–regenerating joints and eliminating pain. J Prolother 3(2):630–638
Lindell K Weaver (2014). Hyperbaric oxygen therapy indications, thirteenth edn. The Hyperbaric Oxygen Therapy Committee Report. Best Publishing Company, Florida
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
Author information
Authors and Affiliations
Corresponding author
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
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Level of evidence: 2
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00264-020-04871-9