3rd International Symposium in O3 Ozone Applications
O3 Ozone in Biology
Ozone in Medicine - June 27th 24th to 30th, 2000
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OZ-L-029: BIOCHEMICAL MECHANISMS PRESENT IN MEDICAL O3 OZONE APPLICATIONS.
Ozone Research Center.
Ozone (O3) biological effects remains controversial due to the scarce knowledge of its biochemical and pharmacodynamic mechanisms. Taking into account that medical ozone applications gather strength, day by day, and it has been used in apparently nonrelated diseases with beneficial effects, is necessary to study the pharmacological actions, as well as its biochemical mechanisms. In this lecture is presented all the knowledge that exist, in the ozone mechanism of action by means of the different therapeutic properties of this dual molecule.
On the basis of the oxidant properties of ozone, we postulate that controlled ozone administration is able to promote an oxidative preconditioning or oxidative stress adaptation, preparing the host to face physiopathological conditions mediated by reactive oxygen species.
An activation of enzymes involved in peroxide or oxygen scavenging is achieved. This possibility of upregulate the antioxidant system have been demonstrated in different pathologies: retinitis pigmentosa, ischemic cardiopathy, arterial insufficiencies, asthma, glaucoma, senile dementia, vascular strokes and in ischaemia-reperfusion phenomenom.
Ozone therapy can activate the citric acid cycle, with a direct influence on the mitochondrial transport system and also, increase blood fluidity, arterial PO2 and red blood cell pliability. The influence that this therapy exerts in different biochemical parameters, fundamentally in the lipidic profile, demonstrating that ozone can act as a metabolic modulator, as well as in the release of certain eicosanoids is discussed.
Also, the influence that ozone exerts in the immunological system, as a bland inducer of several cytokines, as well as the different hypothesis about its germicidal power is been analyzed here. This lecture contributes to clarify the ozone mechanism of action and its different pharmacodynamic effects.
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OZ-L-030: INTRACELLULAR SIGNAL TRANSDUCTION MEDIATED BY O3 OZONE THERAPY.
Ozone Research Center.
Signal transduction is the principal mechanism regulating the metabolic activity in all cells. Therefore, signal transduction is involved in the enzyme activation and/or inhibition, protein and metabolite synthesis, energy production, and other physiological processes needed for cellular survival. However, signal transduction is also involved in the cell deleterious effects such as inflammation, cell degeneration, necrosis and apoptosis.
Ozone therapy has been proposed as an antioxidant enzyme system activator, immunomodulator and cellular metabolic activator. All of these actions are normally triggered from signal transductions in the cell. Ozone therapy role, on intracellular signal transduction, from the point of view of its beneficial or toxic effects, is analyzed in this lecture.
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OZ-L-031: MECHANISM OF OXIDATIVE PRECONDITIONING OZONE PROTECTION HEPATOCELLULAR.THERAPEUTIC IMPLICATIONS.
Center for Biologics Evaluation and Research Institute of Pharmacy and Food.
Basic studies aimed at understanding the pharmacodynamics of ozone have continued to develop and the results of each new experimental design confirm that the pharmacological effects of ozone are associated, among others, the regulation of oxidative stress. We discuss and analyze the main results obtained in different experimental models of hepatocellular damage, chemically and surgically induced.
Protective actions are demonstrated ozone rectally administered from the biochemical point of view and by histology. The comparative analysis between ischemic preconditioning and oxidative preconditioning for ozone, showed the superiority of ozone histologically as a mediator of oxidative reconditioning.
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OZ-PO-032: EFFECT ON PROPHYLAXIS OF OZONE LEVELS OF CALCIUM AND OTHER OXIDATIVE STRESS MEDIATOR IN LIVER AND INFLUENCE subcellular fractions of eicosanoids ON OXIDATIVE PRE-CONDITIONING.
Center for Research and Evaluation Biology, Institute of Food and Drugs.
The use of ozone as pharmacotherapeutic concept is controversial, considering their actions as environmental pollution and the lung. However, its efficacy has been demonstrated in a number of pathologies, all associated with the generation of reactive oxygen species (eros), although it remains unknown how he is able to exert its pharmacological action.
In 1995, ICVA, it was shown that this treatment is administered under controlled conditions, is able to protect liver cells against damage induced by CCl 4 through a process of oxidative preconditioning.
Later in 1996 showed its role in maintaining calcium concentrations in liver homogenates in the same experimental model. Given these results we decided to evaluate the influence of this therapy in liver subcellular organelles associated with the generation of free radicals, which are also important stores of calcium.
The results obtained show that ozone regulates calcium levels in subcellular fractions studied (cytosolic, mitochondrial and microsomal), preventing further by controlling the content of this cation enhancement of hepatocellular damage mediated by degradative enzymes of the cell structure.
The administration of this gas also prevents the development of other oxidative processes, by controlling which states the formation of eicosanoids. Its prophylactic effects were evidenced by its action on the formation of fructosamine, the activity of antioxidant enzymes and malondialdehyde content.
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OZ-PO-033: preconditioning EFFECT OF OZONE ON THE RENAL AND SOME morphofunction MEDIATOR OF OXIDATIVE STRESS IN ISCHEMIC KIDNEY DAMAGE UNDER.
Ozone Research Center,
Institute of Preclinical Basic Sciences,
Center for Biologics Evaluation and Research Institute of Pharmacy and Food.
It is well established that 30 min ischemia followed by reperfusion of the kidney by various mechanisms affecting the overall operation of the nephron to be the main target of ischemic injury of proximal tubule epithelial cells.
Despite this damage the epithelial cells of the nephron provided they retain their stroma are able to regenerate and support this ischemic injury. In clinical situations exist where ischemic time is greater than 30 min and that's where acute kidney injury is more severe.
In this paper our aim was to assess the effect precondicionativo ozone rectally administered on Wistar rat kidneys subjected to ischemia for 60 min followed by 3 h of reperfusion. As a measure of renal function determined the plasma clearances of inulin and hippuric acid-paraamino, assessing glomerular filtration rate and renal plasma flow, respectively.
Proxidantes agents determined the thiobarbituric acid reactive substance and conjugated dienes and antioxidant agents derterminaron reduced glutathione and the enzymes catalase, superoxide dismutase and glutathione peroxidase.
The results showed that the group treated with ozone values remained plasma clearances of inulin and hippuric acid-paraamino similar to healthy control, the behavior showed histologic structural lesions were significantly lower in the group treated with ozone. Regarding the determination of these indicators of oxidative stress showed equivalent results.
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OZ-PO-034: OZONE AS AN ANTIBIOTIC MODULATOR IN LETHAL peritonitis.
S. Schulz (a), Z. Zamora (b), S. Menéndez (b), R. Mutters (a), M. Bette (a)
(a) Veterinary Service, Institute of Medical Microbiology and Institute of Anatomy and Cellular Biology of the Philipps University of Marburg / L Germany.
(B) Ozone Research Center.
The purpose of this study was, first, to demostrate some effects of intraperitoneally ozonized oxygen application on the course of lethal septic peritonitis, and second, if it is beneficial, to combine ozone (pre-treatment) with different immunomodulating antibiotics.
Ozone has complex actions on biological systems like that on the immunsystem, thus modulating the cytokine production/release, which could be beneficial or detrimental on the outcome of survival in the model of lethal peritonitis in rats.
Ozone is a substance with a well-known microbiocidal activty in vitro, but hitherto there are no, or only few in vivo studies with ozone in the model of a polymicrobial septic peritonitis.
From experiment 1 (ozone-pretreatment: -5 to -1 d) (groups A-E): the survival rate was highest in 56 % (E) in those previously treated with 10 m g/mL ozone; in 34 % (D) in those having received 50 m g/mL ozone, and 23 % (C) in those with 100 m g/mL in comparison to 5 % (A) in untreated rats, or in 16 % (B) treated with medical oxygen.
Experiment 2 and 3 (ozone + antibiotic: -5 d to -1 d + 0h + 1h ) (group F-U): the survival rate for ozone + Cefodizine was 66 and 56 % in direct comparison to Cefodizine with 0 % survival, for ozone + Cefatoxime it was 56 and 78 % vs 23 and 17 % without ozone pretreatment; the survival rate for ozone +Levofloxacin was 89 and 56 % vs 12 and 22 % without ozone, and for ozone +Piperacillin/Tazobactam it was 100 and 78 % vs 0 % survival without ozone.
Ozonized oxygen might help to prevent lethal peritonitis (prophylaxis). Furthermore, it enhanced the effectivity of different antibiotics significantly. If ozone can also be used as a new strategy to treat a polymicrobial sepsis is now under investigation.
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OZ-PO-035: USE OF OZONE FOR THE ESTIMATION OF THE DISTRIBUTION OF THE TOTAL UNSATURATION IN LIPID COMPONENTS OF ERYTHROCYTES FOR THE DIFFERENTIAL DIAGNOSTIC OF DIABETES MELLITUS IN CHILDREN.
T.I. Poznyak (a), E.V. Kiseleva b) and T.I. Turkina (c).
(a) Superior School of Chemical Engineering, National Polytechnic Institute of Mexico
(ESIQIE-IPN) Mexico,
(b) Department of Polymers and Composite Materials, Institute of Chemical Physics of Russian Academy of Sciences, Moscow,
(c) Medicine Academy, Moscow, Russia.
Medical ozone therapy is used in the medical practice of various countries. The ozone application in medicine for the diagnostic purposes in different diseases and in the case of pathology at clinics is not so common.
At present, the clinic indices of lipid peroxidation (LPO) are widely used as diagnostic and prognostic criterion for treatment of mentioned patient’s contingent.However, this criterion is not suitable for monitoring the patient’s condition because of the time-consuming complex analysis.
The estimation of the total unsaturation (TU) of plasma (DB-index) and cell membrane (DBcell- index) lipids is a promising method for the testing of various pathologies. This method consists of measuring the ozone absorbed by lipid double bonds according to the ozonation reaction. The quantity of absorbed ozone is the measure of the TU of plasma and cell membrane lipids.
Using ozonation and thin-layer chromatography the qualitative and quantitative correlation of unsaturation distribution (UD) in individual fractions of erythrocytes lipids in children suffering from insulin-dependent diabetes mellitus (IDDM) are determined.
The research was aimed at the elucidation of biochemical criterion of the degree of metabolic disorders in children with IDDM and at the development of new technique for the quantitative assessment of such disorders. Forty-five children, 7-15 years old were examined during the compensation stage (group 1: 17 children) and decompensation stage with ketoacidosis (group 2: 28 children).
The present investigation shows that in the case of IDDM in children the total unsaturation distribution (TUD) in the erythrocyte lipid fractions were found to be increase significantly compared to the control group. The pattern of TUD in the erythrocyte lipid fractions may serve as a biochemical criterion of differential diagnostic in clinical analysis. It can be use to indicate the metabolic disorders and the decompensation degree in patients with IDDM.
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OZ-PO-036: BIOLOGICAL EFFECTS OF OZONE AND RADIATION THERAPY IN MALIGNANT NEOPLASIA: EXPERIMENAL RESEARCH.
T. Scherbatyuk, I. Ivanova, Y. Yakovleva, I. Skvorchova.
Medical Academy, Nizhni Novgorod, Russia.
The aim of this work was to study the biological effects that produces the ionizing radiation in combination with ozone therapy. The mechanisms of cell injury produced by radiation are connected to processes including development of free-radicals oxidation reactions in cellular membranes.
In our opinion, the application of radical therapy, in conjunction with ozone therapy, will result not only in rising selectivity of the ionizing radiations, but also intensifying free-radical environment of tumour. 280 white male rats were used in our experiment. The neoplasia was modelled through lymphosarcoma clone inoculation.
The animals were subject to the following actions: monoradial influence, intra-abdominally, intra-and para-tumourally oxygen influence and gamma-irradiation; intra-abdominally, intra-and para-tumourally ozone influence and gamma-irradiation. The radiation dose was 5 gp.
Ozonated physiological saline was used with an ozone concentration of 128, 864 and 4800 mcg/L. State of free-radicals and antioxidant processes; glycometabolism; endotoxemia; phagocytosis; erythrocytes electrophoretic motility and erythrocytes aggregation were determined in blood and homogenates of tumour and spleen tissues. Morphological and histological changes of tissues were observed. The results of the biological effects of ozone and radiation therapy are discussed.
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OZ-PO-037: NEUROPHYSIOLOGICAL AND BIOCHEMICAL EFFECTS OF OZONIZED SOLUTIONS APPLICATION IN EXPERIMENTS WITH CATS.
S.Kotov; A.Edeleva and A.Mochalov.
Nizhni Novgorod Medical State Academy. Russia.
In the mechanism of the biological action of ozone there are many obscure questions concerning its immediate influence on the nervous tissue. The aim of this research is to study, in experimental conditions, the influence of an ozonized solution containing middle therapeutic concentration of ozone in the somatosensory caused potential (SP), in the enzyme activity of the aerobic metabolism and in the contents of peroxidation lipid products in a somatosensory zone of the cortex in cats brain.
The registration of the caused potential was made on an open brain of 13 adult cats which received intraperitoneal nembutalo-chlorosoli narcosis. With this purpose an electrical boring rendered branches of the radial nerve in the area of the wished joint. Consecutive application of nonozonized and ozonized solution was carried out. In subsequent, the site of the brain was exposed to biochemical researches.
The ozonized solution causes a peak latence decrease of a negative phase in caused potentials to 85 %, from an initial level, in combination with a convertible short-term (10 min) augmentation of the positive phase amplitude in caused potential (26 %). Simultaneously, insignificant raises of the initial peroxidation lipid products were obtained in the researched site of the brain.
The enzymes activity of the respiratory chain does not change simultaneously with the appreciable intensifying of oxidoreductases, activity such as: lactat- dehydrogenases, piruvatdehydrogenases, succinatedehydrogenases.
The ozonized solution stimulates the aerobic glycolysis, raises functional neurones activity of the top cortical layers, not rendering any toxic effect on the excitability and conduction of the nervous tissue
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Source: Ozone Research Center
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