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Cellular and Molecular Mechanisms of Ozone Therapy: Present Knowledge and Prospective Applications

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 24714

Special Issue Editors

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
Interests: ozone therapy; aging; muscle atrophy/dystrophy; multimodal imaging; cell biology
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
Interests: ozone therapy; cell biology; muscle atrophy/dystrophy; nanomedicine; microscopy techniques

Special Issue Information

Dear Colleagues,

Ozone therapy is a complementary, adjuvant or palliative medical treatment consisting in the administration of oxygen–ozone mixtures. In recent decades, this therapy has increasingly been applied all over the world but, despite the wide scientific evidence of the therapeutic potential of ozone treatment, the mechanistic explanation of its positive effects is still incomplete.

This Special Issue aims at illustrating established and novel knowledge on the cellular and molecular mechanisms accounting for the observed successful application of ozone therapy to many different pathological conditions.

We invite researchers of all fields—physicians, pharmacologists, biologists, chemists, etc.—to present their results and propose prospective applications by contributing original research articles or review papers. Manuscripts may deal with the findings obtained on patients or animal models in vivo as well as on tissues and cells in vitro.

Prof. Manuela Malatesta
Dr. Barbara Cisterna
Dr. Manuela Costanzo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antioxidant response
  • cell growth
  • enzyme activity
  • gene expression
  • immune response
  • inflammation
  • metabolic state
  • mitochondrial activity
  • oxidative stress
  • regeneration pathways

Published Papers (6 papers)

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Editorial

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2 pages, 180 KiB  
Editorial
Cellular and Molecular Mechanisms of Ozone Therapy: Present Knowledge and Prospective Applications
Int. J. Mol. Sci. 2022, 23(20), 12586; https://doi.org/10.3390/ijms232012586 - 20 Oct 2022
Cited by 1 | Viewed by 1190
Abstract
As a complementary, adjuvant or palliative cure, ozone therapy has increasingly been used globally on a wide variety of diseases [...] Full article

Research

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16 pages, 2256 KiB  
Article
Therapeutic Treatment of Superoxide Dismutase 1 (G93A) Amyotrophic Lateral Sclerosis Model Mice with Medical Ozone Decelerates Trigeminal Motor Neuron Degeneration, Attenuates Microglial Proliferation, and Preserves Monocyte Levels in Mesenteric Lymph Nodes
Int. J. Mol. Sci. 2022, 23(6), 3403; https://doi.org/10.3390/ijms23063403 - 21 Mar 2022
Cited by 5 | Viewed by 3414
Abstract
Amyotrophic lateral sclerosis (ALS) is an incurable and lethal neurodegenerative disease in which progressive motor neuron loss and associated inflammation represent major pathology hallmarks. Both the prevention of neuronal loss and neuro-destructive inflammation are still unmet challenges. Medical ozone, an ozonized oxygen mixture [...] Read more.
Amyotrophic lateral sclerosis (ALS) is an incurable and lethal neurodegenerative disease in which progressive motor neuron loss and associated inflammation represent major pathology hallmarks. Both the prevention of neuronal loss and neuro-destructive inflammation are still unmet challenges. Medical ozone, an ozonized oxygen mixture (O3/O2), has been shown to elicit profound immunomodulatory effects in peripheral organs, and beneficial effects in the aging brain. We investigated, in a preclinical drug testing approach, the therapeutic potential of a five-day O3/O2i.p. treatment regime at the beginning of the symptomatic disease phase in the superoxide dismutase (SOD1G93A) ALS mouse model. Clinical assessment of SOD1G93A mice revealed no benefit of medical ozone treatment over sham with respect to gross body weight, motor performance, disease duration, or survival. In the brainstem of end stage SOD1G93A mice, however, neurodegeneration was found decelerated, and SOD1-related vacuolization was reduced in the motor trigeminal nucleus in the O3/O2 treatment group when compared to sham-treated mice. In addition, microglia proliferation was less pronounced in the brainstem, while the hypertrophy of astroglia remained largely unaffected. Finally, monocyte numbers were reduced in the blood, spleen, and mesenteric lymph nodes at postnatal day 60 in SOD1G93A mice. A further decrease in monocyte numbers seen in mesenteric lymph nodes from sham-treated SOD1G93A mice at an advanced disease stage, however, was prevented by medical ozone treatment. Collectively, our study revealed a select neuroprotective and possibly anti-inflammatory capacity for medical ozone when applied as a therapeutic agent in SOD1G93A ALS mice. Full article
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16 pages, 3250 KiB  
Article
Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro
Int. J. Mol. Sci. 2021, 22(18), 10133; https://doi.org/10.3390/ijms221810133 - 20 Sep 2021
Cited by 8 | Viewed by 2373
Abstract
Oxygen–ozone (O2–O3) therapy is increasingly applied as a complementary/adjuvant treatment for several diseases; however, the biological mechanisms accounting for the efficacy of low O3 concentrations need further investigations to understand the possibly multiple effects on the different cell [...] Read more.
Oxygen–ozone (O2–O3) therapy is increasingly applied as a complementary/adjuvant treatment for several diseases; however, the biological mechanisms accounting for the efficacy of low O3 concentrations need further investigations to understand the possibly multiple effects on the different cell types. In this work, we focused our attention on fibroblasts as ubiquitous connective cells playing roles in the body architecture, in the homeostasis of tissue-resident cells, and in many physiological and pathological processes. Using an established human fibroblast cell line as an in vitro model, we adopted a multimodal approach to explore a panel of cell structural and functional features, combining light and electron microscopy, Western blot analysis, real-time quantitative polymerase chain reaction, and multiplex assays for cytokines. The administration of O2–O3 gas mixtures induced multiple effects on fibroblasts, depending on their activation state: in non-activated fibroblasts, O3 stimulated proliferation, formation of cell surface protrusions, antioxidant response, and IL-6 and TGF-β1 secretion, while in LPS-activated fibroblasts, O3 stimulated only antioxidant response and cytokines secretion. Therefore, the low O3 concentrations used in this study induced activation-like responses in non-activated fibroblasts, whereas in already activated fibroblasts, the cell protective capability was potentiated. Full article
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15 pages, 4982 KiB  
Article
Ozone in Medicine. The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases
Int. J. Mol. Sci. 2021, 22(15), 7890; https://doi.org/10.3390/ijms22157890 - 23 Jul 2021
Cited by 39 | Viewed by 5044
Abstract
Low-dose ozone acts as a bioregulator in chronic inflammatory diseases, biochemically characterized by high oxidative stress and a blocked regulation. During systemic applications, “Ozone peroxides” are able to replace H2O2 in its specific function of regulation, restore redox signaling, and [...] Read more.
Low-dose ozone acts as a bioregulator in chronic inflammatory diseases, biochemically characterized by high oxidative stress and a blocked regulation. During systemic applications, “Ozone peroxides” are able to replace H2O2 in its specific function of regulation, restore redox signaling, and improve the antioxidant capacity. Two different mechanisms have to be understood. Firstly, there is the direct mechanism, used in topical treatments, mostly via radical reactions. In systemic treatments, the indirect, ionic mechanism is to be discussed: “ozone peroxide” will be directly reduced by the glutathione system, informing the nuclear factors to start the regulation. The GSH/GSSG balance outlines the ozone dose and concentration limiting factor. Antioxidants are regulated, and in the case of inflammatory diseases up-regulated; cytokines are modulated, here downregulated. Rheumatoid arthritis RA as a model for chronic inflammation: RA, in preclinical and clinical trials, reflects the pharmacology of ozone in a typical manner: SOD (superoxide dismutase), CAT (catalase) and finally GSH (reduced glutathione) increase, followed by a significant reduction of oxidative stress. Inflammatory cytokines are downregulated. Accordingly, the clinical status improves. The pharmacological background investigated in a remarkable number of cell experiments, preclinical and clinical trials is well documented and published in internationally peer reviewed journals. This should encourage clinicians to set up clinical trials with chronic inflammatory diseases integrating medical ozone as a complement. Full article
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Review

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12 pages, 597 KiB  
Review
Systemic Review: Ozone: A Potential New Chemotherapy
Int. J. Mol. Sci. 2021, 22(21), 11796; https://doi.org/10.3390/ijms222111796 - 30 Oct 2021
Cited by 9 | Viewed by 5312
Abstract
In the last sixty years, publications in reputed journals have shown the preclinical positive effect of ozone gas in cancer cells. However, the translation of these results into clinical practice is far away from success. A comprehensive approach is necessary for this, and [...] Read more.
In the last sixty years, publications in reputed journals have shown the preclinical positive effect of ozone gas in cancer cells. However, the translation of these results into clinical practice is far away from success. A comprehensive approach is necessary for this, and oncologists and researchers need guidance from medical specialists with in-depth knowledge of ozone in medicine. In this article, we review the evidence around this question and suggest different potential research lines to those interested in this exciting field. Full article
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13 pages, 627 KiB  
Review
Ozone as Modulator of Resorption and Inflammatory Response in Extruded Nucleus Pulposus Herniation. Revising Concepts
Int. J. Mol. Sci. 2021, 22(18), 9946; https://doi.org/10.3390/ijms22189946 - 14 Sep 2021
Cited by 14 | Viewed by 5577
Abstract
Ozone therapy has been used to treat disc herniation for more than four decades. There are several papers describing results and mechanism of action. However, it is very important to define the characteristics of extruded disc herniation. Although ozone therapy showed excellent results [...] Read more.
Ozone therapy has been used to treat disc herniation for more than four decades. There are several papers describing results and mechanism of action. However, it is very important to define the characteristics of extruded disc herniation. Although ozone therapy showed excellent results in the majority of spinal diseases, it is not yet fully accepted within the medical community. Perhaps it is partly due to the fact that, sometimes, indications are not appropriately made. The objective of our work is to explain the mechanisms of action of ozone therapy on the extruded disc herniation. Indeed, these mechanisms are quite different from those exerted by ozone on the protruded disc herniation and on the degenerative disc disease because the inflammatory response is very different between the various cases. Extruded disc herniation occurs when the nucleus squeezes through a weakness or tear in the annulus. Host immune system considers the nucleus material to be a foreign invader, which triggers an immune response and inflammation. We think ozone therapy modulates this immune response, activating macrophages, which produce phagocytosis of extruded nucleus pulposus. Ozone would also facilitate the passage from the M1 to M2 phase of macrophages, going from an inflammatory phase to a reparative phase. Further studies are needed to verify the switch of macrophages. Full article
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