Biological Effects Ozone

The Following is a Short List on

the Biological Effects Ozone Therapy

 

1. Induction of interferon gamma on human leucocytes.

Author
Bocci V; Paulesu L
 
Address
Istituto di Fisiologia Generale, Universit?di Siena, Italy.
 
Source
Haematologica, 1990 Nov-Dec, 75:6, 510-5

Abstract  

In this study we have investigated the effects of ozone on human blood, as well as on resuspended buffy coats and Ficoll-purified mononuclear cells. Samples were exposed at different ozone concentrations (from 2.2 micrograms to 108 micrograms/ml) for 30 sec and then incubated for different times at 37 degrees C in a 95% air-5% CO2 humidified atmosphere. Supernatants were collected and frozen at-20 degrees C until tested for interferon (IFN) activity. We have determined that the ozone concentration is critical for lymphokine induction. In fact, while low concentrations (2.2 micrograms/ml) are effective in lymphocytes, they do not induce IFN in either whole or diluted (1:1) human blood, or resuspended buffy coats. In such cases levels as high as 42 micrograms/ml are required. On the other hand, a very high ozone concentration (108 micrograms/ml) is not effective andprobably toxic. Maximal IFN production occurs 72-96 h after ozone exposure, and the kinetics of IFN release is similar to that after Staphylococcal Enterotoxin B addition. Because ozonization of blood is a medical procedure followed in several countries for treatment of viral diseases, this study can open a new field of investigation that may yield useful results both in biological and practical terms.
 
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2. Induction of tumor necrosis factor (TNF-alpha) on human leucocytes.

Source 
Lymphokine Cytokine Res 1991 Oct; 10(5):409-412
 
Author
Paulesu L, Luzzi E, Bocci V
 
Address
Institute of General Physiology, University of Siena, Italy.

Abstract

The effect of ozone as a probable inducer of tumor necrosis factor (TNF-alpha) has been investigated on human blood and on Ficoll-purified blood mononuclear cells (PBMC). Samples were exposed at different ozone concentrations ranging from 2.2 to 108 micrograms/ml and incubated at 37 degrees C in an 95% air-5% CO2 atmosphere. At predetermined times, all cell supernatants were tested for TNF activity and some PBMC cultures were examined for DNA synthesis. We have shown that ozone concentration is critical in terms of TNF production and of cell mitogenesis and that, owing to the presence of erythrocytes, higher ozone concentrations are required to be effective in blood than in PBMC. Because ozonization of blood is a procedure followed in several European countries for the treatment of viral diseases and tumors, the release of factors with antiviral and immunomodulatory activities by leukocytes may explain the mechanism of action of ozone and of autohemotherapy.
 
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 3. An attempt to define conditions for optimal induction of cytokines.  

Source  
Lymphokine Cytokine Res, 1993 Apr, 12:2, 121-126
 
Author  
Bocci V; Luzzi E; Corradeschi F; Paulesu L; Di Stefano A
 
Address  
Institute of General Physiology, Faculty of Pharmacy, University of Siena, Italy.

Abstract  

Ozonization of blood, normally carried out with citrated blood, may be fine for the autohemotherapy of ischemic diseases but it may be at a loss when employed in viral diseases or in immunodeficiencies. We have shown that heparin, used as an anticoagulant, with the addition of 5 mM CaCl2 favors production of cytokines by leukocytes with only a modest increase in hemolysis. High plasmatic levels of glucose, glutathione, and ascorbic acid decrease cytokine’s yield because these compounds act as antioxidants and quench the inducing activity of ozone. Autohemotherapy with heparinized and Ca(2+)-supplemented blood has not revealed any side effects in volunteers.
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4. Cytokine production and glutathione levels in human erythrocytes.  

Source  
J Biol Regul Homeost Agents, 1993 Oct-Dec, 7:4, 133-138
 
Author  
Bocci V; Luzzi E; Corradeschi F; Paulesu L; Rossi R; Cardaioli E; Di Simplicio P
 
Address  
Institute of General Physiology, Faculty of Pharmacy, University of Siena, Italy.

Abstract  

We have investigated the effect of various concentrations of ozone on human blood aiming to correlate the production of cytokines with depletion of reduced glutathione and hemolysis. As erythrocytes constitute the bulk of blood cells and represent the main target of ozone they have been taken as a useful marker of its oxidative activity. It appears that a transient exposure (30 sec) of blood of up to 78 micrograms ozone per ml of blood does not depress the production of cytokines even though there is a slight increase of hemolysis and a small decrease of intracellular reduced glutathione. In contrast either a constant (up to 30 sec) exposure to an ozone flux or a high ozone concentration (108 micrograms/ml) markedly decreases reduced glutathione levels and depresses cytokine production.
 
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5. Evaluation of immunological parameters and tolerability in normal volunteers receiving ambulatory autohemotherapy.


Source
Biotherapy 1993;7(2):83-90  
 
Author
Bocci V, Luzzi E, Corradeschi F, Paulesu L
 
Address
Faculties of Pharmacy, Institute of General Physiology, Siena, Italy.

Abstract

Autohemotherapy, after a bland treatment ex vivo of blood with ozone, is a fairly unknown medical procedure claimed to have therapeutic value in viral diseases and neoplasms. Having already shown that ozone acts as a mild inducer of cytokines, we have undertaken an investigation in normal rabbits and in normal volunteers aiming to evaluate eventual changes of some cytokine levels in plasma as well as of immunological parameters such as the Mx protein, neopterin, beta 2-microglobulin and of some acute-phase proteins after single or repeated autohemotherapy. We have also evaluated the potential development of side-effects. This study is the first one to show that autohemotherapy can activate an immunological marker in normal subjects without procuring any toxic effects.
 
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6. Production of transforming growth factor 1 by human blood after ozone treatment.

Source
J Biol Regul Homeost Agents, 1994 Oct-Dec, 8:4, 108-112
 
Author
Bocci V; Luzzi E; Corradeschi F; Silvestri S
 
Address
Institute of General Physiology and Nutritional Sciences, Siena, Italy.

Abstract  

After exposing human whole blood from normal volunteers to ozone concentrations ranging from 22 to 156 micrograms/ml, we have shown that, upon incubation of up to 8 hours, there is a significant release of transforming growth factor beta (TGF-beta 1). In comparison to TGF-beta 1, TGF-beta 2 production is not influenced by ozone concentrations. In line with our previous findings it appears that blood, in the presence of heparin and 5mM Ca,2+ allows a consistent production of tumor necrosis factor a (TNF alpha) and the release of low and non-hazardous levels of free hemoglobin. These data support the contention that autohemotherapy performed after treating blood with ozone followed by reinfusion into the donor, may represent a valuable therapeutic approach for achieving immunoregulatory effects.
  
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7. Ozonization of blood for the therapy of viral diseases and immunodeficiencies. A hypothesis.

Source
Med Hypotheses 1992 Sep; 39(1):30-34
  
Author
Bocci V
 
Address
Institute of General Physiology and Nutritional Sciences, University of Siena, Italy.

Abstract

In the last 3 decades major autohemotherapy after exposure to ozone has been used in Europe in uncontrolled trials carried out in patients with many illnesses, particularly chronic viral diseases and neoplasms. It appears that the treatment may activate the host’s immune system by inducing the production of immunoactive cytokines and it may now be possible to rationalize the procedure, improve the regimen and assess the outcome. It is apparent, however, that such a therapeutic approach, in order to be acceptable, requires an investigative effort of biologists and clinicians. Once this is done, owing to the large range of medical applications and the simplicity of the procedure, autohemotherapy could become very valuable particularly in underdeveloped countries.
 
 
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8. Does ozone therapy normalize the cellular redox balance? Implications for therapy of human immunodeficiency virus infection and several other diseases.

Source
Med Hypotheses 1996 Feb; 46(2):150-154
 
Author
Bocci V
 
Address
Institute of General Physiology; University of Siena, Italy.

Abstract

The role of ozone on earth is controversial, as in the stratosphere it is protective against excessive ultra violet irradiation, and in the troposphere it is toxic for animals and plants. The effectiveness of ozone against pathogens is well recognized and ozone appears to be the best agent for sterilization of water. In spite of this, the use of ozone in medicine has been overlooked or despised, mostly because it has been either misused or used without appropriate controls. Studies carried out in our laboratory have revealed that ozone can display relevant biological effects and that, having defined its therapeutic index, can become an important and reliable drug for the treatment of several diseases. An exciting new aspect is that ozone, being a strong oxidizer, can stimulate the increase of cellular anti-oxidant enzymes, eventually inhibiting the oxidative stress.
 
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9. Autohemotherapy after treatment of blood with ozone. A reappraisal.

Source  
J Int Med Res, 1994 May-Jun, 22:3, 131-144
 

Author  
Bocci V
 
Address
Institute of General Physiology, University of Siena, Italy.

Abstract  

Autohemotherapy, involving bland treatment ex vivo of blood with ozone and prompt reinfusion into the donor, is a procedure mainly performed in central Europe, which is claimed to have therapeutic value in circulatory disorders, viral diseases and cancer. This practice is mostly performed in private clinics, and good clinical trials have not been published, which has understandably given rise to prejudice and scepticism. By analysing possible mechanisms of action and current hypotheses, this report attempts to explain how this procedure can be useful in such disparate diseases. The current state of the art is presented objectively, the lack of toxicity is documented, and the rationale and therapeutic advantages are discussed, with the aim of eliciting interest in carrying out controlled
clinical trials.
 
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10. Ozone as a bioregulator. Pharmacology and toxicology of ozonetherapy today.

Source  
J Biol Regul Homeost Agents 1996 Apr; 10(2-3):31-53
 
 
Author
Bocci V
 
Address
Institute of General Physiology, University of Siena, Italy.

Abstract

The disinfectant activity of ozone is well recognized and ozone is used worldwide for sterilization of water. The use of ozone as a complementary medical approach is less known, because it has mostly been used in an empirical fashion without a rational basis and appropriate controls. In spite of this drawback, the use of judicious and standardized ozone dosages can elicit the formation of ROS acting as natural physiological activators of several biological functions. There is now a reasonable understanding of a few mechanisms of action and, using classical pharmacological concepts, it appears possible to formulate a rationale for optimizing clinical applications. A further exciting development is that ozone, being an oxidizer, can upregulate the intracellular anti-oxidant enzymes eventually inhibiting the constant, life-long oxidative stress responsible for degenerative diseases and aging. Among various routes for the administration of ozone, the autohemotransfusion procedure, consisting in exposing blood to ozone, i.e. to a calculated and brief oxidative stress, appears safe, simple, inexpensive and amenable to be adjusted to different pathological states It is hoped that this review will help to dispel prejudices, to clarify that ozone toxicity can be tamed, to show that ozone can act as a bioregulator and to encourage controlled clinical investigations to evaluate definitely the validity of ozonetherapy.
 
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Biological Effects Ozone Therapy or Medical Ozone

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