Ozone as Janus: this controversial gas can be either toxic or medically useful.

Ozone is an intrinsically toxic gas and its hazardous employment has led to a poor consideration of ozone therapy. The aim of this review is to indicate that a wrong dogma and several misconceptions thwart progress: in reality, properly performed ozone therapy, carried out by expert physicians, can be very useful when orthodox medicine appears inadequate. The unbelievable versatility of ozone therapy is due to the cascade of ozone-derived compounds able to act on several targets leading to a multifactorial correction of a pathological state. During the past decade, contrary to all expectations, it has been demonstrated that the judicious application of ozone in chronic infectious diseases, vasculopathies, orthopedics and even dentistry has yielded such striking results that it is deplorable that the medical establishment continues to ignore ozone therapy

Visual Improvement Following Ozonetherapy in Dry Age Related Macular Degeneration; a Review

The dry form of ARMD is becoming a serious problem because of the rise in the number of old individuals. No effective therapy is available in dry ARMD except for the illusory oral administration of antioxidant vitamins. Despite scepticism in the medical community, the therapeutic effect of ozonetherapy had been evaluated since 1996. This evaluation has been based on specific biochemical, molecular and pharmacological reactions. Nevertheless a number of visual scientists continue to ignore ozonetherapy conservatively and prescribe only antioxidant vitamins. Two small clinical studies involving 217 patients have been performed at the University of Siena showing that ozonetherapy can stop the progression of the disease while improving the visual acuity and the well-being of the patient. Moreover, it seems that ozonetherapy is a safe procedure and tends to have an excellent compliance

Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?

The potential mechanisms of action of ozone therapy are reviewed in this paper. The therapeutic efficacy of ozone therapy may be partly due the controlled and moderate oxidative stress produced by the reactions of ozone with several biological components. The line between effectiveness and toxicity of ozone may be dependent on the strength of the oxidative stress. As with exercise, it is well known that moderate exercise is good for health, whereas excessive exercise is not

Visual Improvement Following Ozonetherapy in Dry Age Related Macular Degeneration; a Review

The dry form of ARMD is becoming a serious problem because of the rise in the number of old individuals. No effective therapy is available in dry ARMD except for the illusory oral administration of antioxidant vitamins. Despite scepticism in the medical community, the therapeutic effect of ozonetherapy had been evaluated since 1996. This evaluation has been based on specific biochemical, molecular and pharmacological reactions. Nevertheless a number of visual scientists continue to ignore ozonetherapy conservatively and prescribe only antioxidant vitamins. Two small clinical studies involving 217 patients have been performed at the University of Siena showing that ozonetherapy can stop the progression of the disease while improving the visual acuity and the well-being of the patient. Moreover, it seems that ozonetherapy is a safe procedure and tends to have an excellent compliance

Oxygen/ozone as a medical gas mixture. A critical evaluation of the various methods clarifies positive and negative aspects

Besides oxygen, several other gases such as NO, CO, H2, H2S, Xe and O3 have come to age over the past few years. With regards to O3, its mechanisms of action in medicine have been clarified during the last two decades so that now a comprehensive framework for understanding and recommending ozone therapy in various pathologies is available. O3 used within the determined therapeutic window is absolutely safe and more effective than golden standard medications in numerous pathologies, like vascular diseases. However, ozone therapy is mostly in practitioners' hands and some recent developments for increasing cost effectiveness and speed of treatment are neither standardized, nor evaluated toxicologically. Hence, the aim of this article is to emphasize the need to objectively assess the pros and cons of oxygen/ozone as a medical gas mixture in the hope that ozone therapy will be accepted by orthodox medicine in the near future

Ozone acting on human blood yields a hormetic dose-response relationship

The aim of this paper is to analyze why ozone can be medically useful when it dissolves in blood or in other biological fluids. In reviewing a number of clinical studies performed in Peripheral Arterial Diseases (PAD) during the last decades, it has been possible to confirm the long-held view that the inverted U-shaped curve, typical of the hormesis concept, is suitable to represent the therapeutic activity exerted by the so-called ozonated autohemotherapy. The quantitative and qualitative aspects of human blood ozonation have been also critically reviewed in regard to the biological, therapeutic and safety of ozone. It is hoped that this gas, although toxic for the pulmonary system during prolonged inhalation, will be soon recognized as a useful agent in oxidative-stress related diseases, joining other medical gases recently thought to be of therapeutic importance. Finally, the elucidation of the mechanisms of action of ozone as well as the obtained results in PAD may encourage clinical scientists to evaluate ozone therapy in vascular diseases in comparison to the current therapies

Ozonation of Human Blood Induces a Remarkable Upregulation of Heme Oxygenase-1 and Heat Stress Protein-70

Heme oxygenase-I (HO-1) has emerged as one of the most protective enzymes and its pleiotropic activities have been demonstrated in a variety of human pathologies. Unpublished observations have shown that HO-1 is induced after the infusion of ozonated blood into the respective donors, and many other experimental observations have demonstrated the efficacy of oxidizing agents. It appeared worthwhile to evaluate whether we could better define the activity of potential inducers such as hydrogen peroxide and ozonated human plasma. Human vascular endothelial cells at confluence were challenged with different concentrations of these inducers and the simultaneous production of nitric oxide (NO); and HO-1 was measured by either measuring nitrite, or bilirubin formation, or/and the immune reactivity of the protein by Western blot using a rabbit antihuman HO-1 and Hsp-70. The results show that production of both NO and HO-1 is fairly dose dependent but is particularly elevated using human plasma after transient exposure to a medium ozone concentration. At this concentration, there is also induction of Hsp-70. The results clarify another positive effect achievable by the use of ozone therapy

Nrf2 activation as target to implement therapeutic treatments

A chronic increase of oxidative stress is typical of serious pathologies such as myocardial infarction, stroke, chronic limb ischemia, chronic obstructive pulmonary disease (COPD), type II-diabetes, age-related macular degeneration leads to an epic increase of morbidity and mortality in all countries of the world. The initial inflammation followed by an excessive release of reactive oxygen species (ROS) implies a diffused cellular injury that needs to be corrected by an inducible expression of the innate detoxifying and antioxidant system. The transcription factor Nrf2, when properly activated, is able to restore a redox homeostasis and possibly improve human health

The rectal insufflation is not the best administration route of ozone

To the Editor of the Revista Española de Ozonoterapia We read the letter entitled “Rectal insufflations are a valid way in ozonetherapy” by Martínez-Sánchez et al. (Revista Española de Ozonoterapia. 2012, Vol. 2, nº 1, pp. 233-235) as a feedback  on our article “Oxygen-Ozone Therapy is at a Cross-Road” (Rev. Esp. Ozono. 2011, 1(1): 74-86). As we have been involved in this topic for longer than two decades, we felt the duty to express some reservation about the validity of the ozone administration via rectal route as well as the expanding use of infusing ozonated saline. It is obvious that the ozone administration via rectal route is the most simple and cheap way to administer ozone. However, while the physician intends to administer a total amount of 6 mg, he cannot be ever sure which is the effective ozone dose because: i) in the colorectal lumen there are feces, mucopolysaccharides that variably react and neutralize some of the administered ozone; ii) part of the gas may be involuntarily eliminated. Moreover, it must be clear that the remaining ozone is never absorbed by the rectal mucosa because it immediately reacts with the lining fluid. On the other hand, the generated H2O2 last only about 20 sec and only some peroxidation products can be absorbed and they have been measured in the portal and jugular veins

A realistic evaluation of the action of ozone on whole human blood

We have clarified the role of the ozone concentration in relation to the resistance of human erythrocytes in whole human blood or in blood diluted either in saline or in distilled water. Spectrophotometric data related to haemoglobin were evaluated by exposing samples of fresh human blood directly to ozone doses (ratio 1:1 volume), within the therapeutic range (0.21–1.68 mM) and to one toxic dose (3.36 mM). Furthermore, the same determinations have been carried out after previous dilution of the same blood with either pure water or physiological saline (1 ml blood + 29ml diluent) followed by ozonation with the above reported ozone doses. Addition of either saline or water implies a dilution of plasma antioxidants and also total haemolysis after water dilution. Particularly the latter case represents a most unphysiological situation because the osmotic shock causes the solubilization of the erythrocytic content. While it is possible to demonstrate that after haemolysis there is an ozone-concentration dependent transformation of some oxyhaemoglobin to methaemoglobin, no such process occurs after ozonation of whole blood. The results of this study fully confirm our previous data that judicious ozone doses neither damage erythrocytes, nor induce oxidation of intracellular haemoglobin. We hope that our conclusions will definitively clarify the absence of toxicity of ozonetherapy