Studies On The Biological Effects
Of Ozone
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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Title
Studies on the biological effects of ozone:
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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Title
Studies on the biological effects of ozone:
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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Title
Studies on the biological effects of ozone:
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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Title
Studies on the biological effects of ozone:
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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Title
Studies on the biological effects of ozone:
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 (TN
F 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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Title
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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Title
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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Source
J Int Med Res, 1994 May-Jun, 22:3, 131-144
Title
Autohemotherapy after treatment of blood with ozone. A
reappraisal.
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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Title
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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