Ozone in Medicine. The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases

Viebahn-Haensler, Renate; Fernández, Olga

doi:10.3390/ijms22157890

Cited by 67 publications

(61 citation statements)

References 24 publications

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“…Interestingly, most of the effects observed in non-activated fibroblasts are due to the exposure to 10 or 20 µg O 3 , i.e., the concentrations that have been already found as optimal for safely inducing positive response in various cell models [ 5 , 6 , 7 , 11 , 15 , 16 ]. This perfectly agrees with the low-dose concept in the medical use of O 3 [ 89 , 90 ], which is increasingly applied in clinical practice.…”

Section: Discussionsupporting

confidence: 87%

Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro

Cisterna

Costanzo

Lacavalla

et al. 2021

IJMS

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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.

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Section: Discussionsupporting

confidence: 87%

Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro

Cisterna

Costanzo

Lacavalla

et al. 2021

IJMS

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“…Because the serum HDL is a macromolecular complex of phospholipid, cholesterol, and protein in serum [ 30 ], it can provide a good model to study the influence of ozonated oil on protein and lipid complexes. Recently, it was suggested that ozone peroxides are pharmacologically active substances that can replace H 2 O 2 to restore redox signaling and that can improve the antioxidant capacity [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Ozonated Sunflower Oil Exerted Protective Effect for Embryo and Cell Survival via Potent Reduction Power and Antioxidant Activity in HDL with Strong Antimicrobial Activity

Cho

Kang²,

Nam³

et al. 2021

Antioxidants

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Ozonated sunflower oil (OSO) has potent antimicrobial effects, making it useful for topical applications to treat various skin diseases. On the other hand, regarding mechanistic insight, the antioxidant activity and cytoprotective effects of OSO are relatively less known. The current study compared the antioxidant ability and protective ability of OSO on cells and embryos against oxidative stress, such as H2O2 and oxidized low-density lipoproteins (oxLDL), to investigate its potential applications for wound-healing and anti-infection. OSO showed potent radical scavenging activity and ferric ion reduction ability that was up to 35% and 42% stronger than sunflower oil (SO) as a control in a dose-dependent manner. Measurement of the wavelength-maximum fluorescence (WMF) of high-density lipoproteins (HDL) revealed different behavior between OSO and SO treatment (final 1–16%). The OSO treatment caused a 12 nm red shift of Trp movement from 345 nm (at 0%) to 357 nm (at 16%), while SO caused a 12 nm blue shift of Trp movement from 345 nm (at 0%) to 333 nm (at 16%). The fluorescence intensity of HDL3 was diminished remarkably by the OSO treatment by up to 80% from the initial level, while SO-treated HDL did not. OSO-treated HDL3 showed slower electromobility with stronger band intensity and bigger HDL particle sizes than those of SO-treated HDL3. The paraoxonase-1 (PON-1) activity of HDL3 was enhanced by a co-treatment of OSO that was up to 2.3 times higher than HDL3 alone in a dose-dependent manner, whereas the co-treatment of SO even inhibited the PON activity. The cell viability of RAW264.7 by the OSO treatment was 3.3 times higher than the SO treatment at a high dose range (from 10% to 50%, final). The OSO also exhibited more cytoprotective effects than SO in brain microglial cells in the presence of H2O2 (final 0.03%); treatment with OSO impeded apoptosis and reduced ROS production more than an SO treatment did. In the presence of H2O2 alone, 86 ± 5% of the embryos were killed by cell explosion after 24 h, but a co-treatment of OSO (final 4%) resulted in almost no embryo death (98% survivability). Injection of oxLDL (15 ng of protein) into zebrafish embryos caused acute death, while the co-injection of OSO (final 2%) resulted in 2.8 times higher survivability than oxLDL alone. These results suggest new effects of ozonated oil, such as enhanced antioxidant activity, more cytoprotective ability, and higher embryo protection against oxidative stress. These results may be useful in developing new methods for the quality control of ozonated oil and an assessment of its efficacy.

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“…It appears clear that blood, in comparison to the corresponding plasma, is far less sensitive to ozone oxidation because of the presence of blood cells. The real mechanism of possible self-repair of the cells that have suffered the oxidative insult has not yet been defined, even if the hormesis theory of stress adaptation could represent the cellular response mechanisms to maintain homeostasis and cell survival [ 86 , 87 ].…”

Section: Molecular Aspectsmentioning

confidence: 99%

The Relationship between Ozone and Human Blood in the Course of a Well-Controlled, Mild, and Transitory Oxidative Eustress

Tricarico

Travagli

2021

Antioxidants

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In the last twenty years there has been a proliferation of articles on the therapeutic use of ozone. As it is well-known, the term ozone therapy is very broad. It ranges from either systemic or loco-regional administration of unstable gaseous oxygen/ozone mixtures to the topical application of stable ozonated derivatives. Anyway, in relation to the absence of specific receptors and the extreme reactivity with the biological liquids with which it comes into contact, gaseous ozone cannot be classified as either a drug or a pro-drug. When the gaseous ozone impacts a biological matrix, both reactive oxygen species (ROS) and lipid oxidation products (LOPs) are formed. They represent the effector molecules responsible for modulating the therapeutic activity in the body. Apart from the merits of the action mechanisms resulting from the use of ozone, this article seeks to validate the practice of ozone therapy as an adjuvant treatment in full compliance with the physiology of the whole organism.

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Ozone in Medicine. The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases

Cited by 67 publications

References 24 publications

Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro

Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro

Ozonated Sunflower Oil Exerted Protective Effect for Embryo and Cell Survival via Potent Reduction Power and Antioxidant Activity in HDL with Strong Antimicrobial Activity

The Relationship between Ozone and Human Blood in the Course of a Well-Controlled, Mild, and Transitory Oxidative Eustress

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