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ABSTRACT: The results of the use of ozonised sunflower oil (OLEOZON(®)) in the treatment of onychomycosis, based on its known antimycotic action and good skin tolerance, by means of a controlled randomised phase III assay are presented. A total of 400 outpatients were randomly divided into two groups: experimental, treated with topical OLEOZON(®), two times per day and control, treated also two times per day, with ketoconazole cream 2%, for 3 months. A patient was considered cured when the sick nails regained the normal colour, growth and thickness, with a negative mycological study. In the experimental group, a regression of signs was achieved from the first month of treatment, while in the control group, it was obtained after the third month of treatment. All patients treated with OLEOZON(®) had improvement in their condition (9.5%) or were cured (90.5%). However, in the control group, only 13.5% of patients were cured, 27.5% improved and 59% remained the same, with significant differences between both the groups. After 1 year of follow-up, experimental and control groups presented 2.8% and 44.4% of relapses, respectively. Topical OLEOZON(®) demonstrated effectiveness in the treatment of onychomycosis, superior to that of ketoconazole. No side effects were observed.
Mycoses 09/2011; 54(5):e272-7. · 2.25 Impact Factor
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ABSTRACT: The ischaemia-reperfusion process is largely mediated by reactive oxygen species. Taking into account that a transient and controlled administration of ozone is able to upregulate cellular antioxidant enzymes, a morphological, biochemical and functional renal study was performed in rats undergoing warm renal ischaemia.
Rats were divided into four groups. All except the negative controls underwent 60 min' bilateral renal ischaemia followed by 10 days' reperfusion. The positive control group received no further treatment. The ozone group received an ozone/oxygen mixture (ozone dose 0.5 mg/kg) immediately after the ischaemia and daily for the 10 days' reperfusion; the oxygen group were given the same concentration of oxygen alone (13 mg/kg). Biochemical parameters fructosamine, phospholipase A2, catalase, superoxide dismutase and thiobarbituric acid reactive substances were measured, as well as renal plasma flow and glomerular filtration rate.
Renal plasma flow and glomerular filtration rate decreased significantly in the positive controls and the oxygen group whereas values in the ozone group were similar to those in the negative control group. With respect to the biochemical parameters, ozone maintained a homeostasis redox, with significant increases in catalase and superoxide dismutase activities and similar values for phospholipase A2 and fructosamine compared with the negative control group. Fewer morphological alterations were seen in kidneys from the ozone group. No advantages were obtained in the positive control and oxygen groups.
The protective effect of ozone may be explained by upregulation of the antioxidant defence system and beneficial effects on blood circulation and in oxygen metabolism. Ozone treatment may represent a therapeutic approach for minimising renal damage after transplantation.
Journal of Pharmacy and Pharmacology 03/2009; 61(2):221-7. · 2.17 Impact Factor
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ABSTRACT: Ozone has recently been subjected to criticism and emphasis in relation to clinical efficacy and toxicity, respectively. Without a doubt, ozone, in common with oxygen itself, is one of the most potent oxidants. Ozone is considered one of the major pollutants in urban areas. Nevertheless, increasingly widespread use lately has highlighted the potential benefits as a therapeutic agent when used according to well-defined and safe protocols. Basic studies conducted following rigorous scientific and ethical criteria have been proposed for scientific discussion. This paper concerns original data on an in vivo model of Parkinson's disease and published data on the effect of low ozone doses with any risk of toxicity excluded with the concentrations commonly used in medical applications.
Archives of Medical Research 02/2008; 39(1):17-26. · 1.88 Impact Factor
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ABSTRACT: The liver is damaged by sustained ischemia in liver transplantation, and the reperfusion after ischemia results in further functional impairment. Ozone oxidative preconditioning (OzoneOP) protected the liver against ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the role of A(1) adenosine receptor on the protective actions conferred by OzoneOP in hepatic I/R. By using a specific agonist and antagonist of the A(1) subtype receptor (2-chloro N6 cyclopentyladenosine, CCPA and 8-cyclopentyl-1,3-dipropylxanthine, DPCPX respectively), we studied the role of A(1) receptor in the protective effects of OzoneOP on the liver damage, nitiric oxide (NO) generation, adenosine deaminase activity and preservation of the cellular redox balance. Immunohistochemical analysis of nuclear factor-kappa B (NF-kappaB), tumor necrosis factor alpha (TNF-alpha) and heat shock protein-70 (HSP-70) was performed. OzoneOP prevented and/or ameliorated ischemic damage. CCPA showed a similar effect to OzoneOP + I/R group. A(1)AR antagonist DPCPX blocked the protective effect of OzoneOP. OzoneOP largely reduced the intensity of the p65 expression, diminished TNF-alpha production, and promoted a reduction in HSP-70 immunoreactivity. In summary, OzoneOP exerted protective effects against liver I/R injury through activation of A(1) adenosine receptors (A(1)AR). Adenosine and (.)NO produced by OzoneOP may play a role in the pathways of cellular signalling which promote preservation of the cellular redox balance, mitochondrial function, glutathione pools as well as the regulation of NF-kappaB and HSP-70.
Transplant International 02/2008; 21(1):39-48. · 2.92 Impact Factor
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ABSTRACT: Cellular events in cisplatin-mediated nephrotoxicity include apoptosis induction, decreased protein synthesis, changes in the subcellular redistribution of Bax mitochondrial dysfunction, DNA injury, increased lipid peroxidation, depletion of glutathione and decrease in enzymatic activity of renal antioxidant enzymes. In previous papers we have shown that intra-rectal (i.r.) ozone/oxygen mixture protected and induced a significant recovery in cisplatin-induced renal damage and was related to a significant increase in the antioxidant system in renal tissue.
This study was undertaken to examine the effect of the ir applications of ozone/oxygen mixture in the renal expression pattern of Bax proteins in rats treated with cisplatin. A group of male Sprague-Dawley rats was pretreated with 15 i.r. applications of ozone/oxygen (1.1 mg/kg) before intraperitoneal injection of cisplatin (6 mg/kg). Another group was treated with five i.r. applications of ozone/oxygen mixture after cisplatin administration. Serum creatinine was measured thereafter. Subcellular distribution of Bax in renal tissue was analyzed by immunohistochemistry.
Ozone pretreatment prevented the increase in serum creatinine levels and completely inhibited the acute tubular necrosis induced by cisplatin in renal tissue, diminishing the expression of Bax. Ozone treatment after cisplatin application reduced the increase in serum creatinine levels and the renal necrosis, inducing a lesser decrease of the Bax expression in cisplatin-treated kidneys.
Expression of Bax in renal tissue seems to play an important role in the protection and recovery in cisplatin-nephrotoxicity achieved by ozone/oxygen mixture.
Archives of Medical Research 09/2006; 37(6):717-22. · 1.88 Impact Factor
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ABSTRACT: Oxidative stress is suggested to have an important role in the development of complications in diabetes. Because ozone therapy can activate the antioxidant system, influencing the level of glycemia and some markers of endothelial cell damage, the aim of this study was to investigate the therapeutic efficacy of ozone in the treatment of patients with type 2 diabetes and diabetic feet and to compare ozone with antibiotic therapy. A randomized controlled clinical trial was performed with 101 patients divided into two groups: one (n = 52) treated with ozone (local and rectal insufflation of the gas) and the other (n = 49) treated with topical and systemic antibiotics. The efficacy of the treatments was evaluated by comparing the glycemic index, the area and perimeter of the lesions and biochemical markers of oxidative stress and endothelial damage in both groups after 20 days of treatment. Ozone treatment improved glycemic control, prevented oxidative stress, normalized levels of organic peroxides, and activated superoxide dismutase. The pharmacodynamic effect of ozone in the treatment of patients with neuroinfectious diabetic foot can be ascribed to the possibility of it being a superoxide scavenger. Superoxide is considered a link between the four metabolic routes associated with diabetes pathology and its complications. Furthermore, the healing of the lesions improved, resulting in fewer amputations than in control group. There were no side effects. These results show that medical ozone treatment could be an alternative therapy in the treatment of diabetes and its complications.
European Journal of Pharmacology 11/2005; 523(1-3):151-61. · 2.52 Impact Factor
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ABSTRACT: Chronic renal failure (CRF) represents a world health problem. Ozone increases the endogenous antioxidant defense system, preserving the cell redox state. The aim of this study is to evaluate the effect of ozone/oxygen mixture in the renal function, morphology, and biochemical parameters, in an experimental model of CRF (subtotal nephrectomy). Ozone/oxygen mixture was applied daily, by rectal insufflation (0.5 mg/kg) for 15 sessions after the nephrectomy. Renal function was evaluated, as well as different biochemical parameters, at the beginning and at the end of the study (10 weeks). Renal plasmatic flow (RPF), glomerular filtration rate (GFR), the urine excretion index, and the sodium and potassium excretions (as a measurement of tubular function) in the ozone group were similar to those in Sham group. Nevertheless, nephrectomized rats without ozone (positive control group) showed the lowest RPF, GFR, and urine excretion figures, as well as tubular function. Animals treated with ozone showed systolic arterial pressure (SAP) figures lower than those in the positive control group, but higher values compared to Sham group. Serum creatinine values and protein excretion in 24 hours in the ozone group were decreased compared with nephrectomized rats, but were still higher than normal values. Histological study demonstrated that animals treated with ozone showed less number of lesions in comparison with nephrectomized rats. Thiobarbituric acid reactive substances were significantly increased in nephrectomized and ozone-treated nephrectomized rats in comparison with Sham group. In the positive control group, superoxide dismutase (SOD) and catalase (CAT) showed the lowest figures in comparison with the other groups. However, ozone/oxygen mixture induced a significant stimulation in the enzymatic activity of CAT, SOD, and glutathione peroxidase, as well as reduced glutathione in relation with Sham and positive control groups. In this animal model of CRF, ozone rectal administrations produced a delay in the advance of the disease, protecting the kidneys against vascular, hemorheological, and oxidative mechanisms. This behavior suggests ozone therapy has a protective effect on renal tissue by downregulation of the oxidative stress shown in CRF.
Mediators of Inflammation 09/2005; 2005(4):221-7. · 3.26 Impact Factor
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ABSTRACT: Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-prooxidant balance for preservation of cell redox state by the increase of antioxidant endogenous systems in both in vivo and in vitro experimental models. Our aim is to analyze the effect of ozone oxidative preconditioning on serum TNF-alpha levels and as a modulator of oxidative stress on hepatic tissue in entodoxic shock model (mice treated with lipopolysaccharide (LPS)). Ozone/oxygen gaseous mixture which was administered intraperitoneally (0.2, 0.4, and 1.2 mg/kg) once daily for five days before LPS (0.1 mg/kg, intraperitoneal). TNF-alpha was measured by cytotoxicity on L-929 cells. Biochemical parameters such as thiobarbituric acid reactive substances (TBARS), enzymatic activity of catalase, glutathione peroxidase, and glutathione-S transferase were measured in hepatic tissue. One hour after LPS injection there was a significant increase in TNF-alpha levels in mouse serum. Ozone/oxygen gaseous mixture reduced serum TNF-alpha levels in a dose-dependent manner. Statistically significant decreases in TNF-alpha levels after LPS injection were observed in mice pretreated with ozone intraperitoneal applications at 0.2 (78%), 0.4 (98%), and 1.2 (99%). Also a significant increase in TBARS content was observed in the hepatic tissue of LPS-treated mice, whereas enzymatic activity of glutathion-S transferase and glutathione peroxidase was decreased. However in ozone-treated animals a significant decrease in TBARS content was appreciated as well as an increase in the activity of antioxidant enzymes. These results indicate that ozone oxidative preconditioning exerts inhibitory effects on TNF-alpha production and on the other hand it exerts influence on the antioxidant-prooxidant balance for preservation of cell redox state by the increase of endogenous antioxidant systems.
Mediators of Inflammation 03/2005; 2005(1):16-22. · 3.26 Impact Factor
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ABSTRACT: Ozone therapy has become a useful treatment for pathological processes, in which the damage mediated by reactive oxygen species is involved. Several lines of evidence suggest that cisplatin-induced acute nephrotoxicity is partially mediated by reactive oxygen species
To analyze the effect of ozone administration after cisplatin-induced acute nephrotoxicity.
Male Sprague-Dawley rats were treated with five intra-rectal applications of ozone/oxygen mixture at 0.36, 1.1 and 1.8 mg/kg after cisplatin intraperitoneal injection (6 mg/kg). Serum and kidneys were taken off 5 days after cisplatin treatment. Creatinine was measured in the serum and the activities of antioxidant enzymes and thiobarbituric acid reactive substances and glutathione content were analyzed in renal homogenate.
Ozone treatment diminished the increase in serum creatinine levels, the glutathione depletion and also reversed the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. Also, the renal content of thiobarbituric reactive substances was decreased by ozone/oxygen mixture applied after cisplatin.
Intrarectal applications of ozone reversed the renal pro-oxidant unbalance induced by cisplatin treatment by the way of stimulation to some constituents of antioxidant system in the kidney, and thereby it decreased the renal damage.
Mediators of Inflammation 01/2005; 13(5-6):307-12. · 3.26 Impact Factor
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ABSTRACT: Acute renal failure is a dose-limiting factor of cisplatin chemotherapy. Here, we show the protective effect of ozone oxidative preconditioning against cisplatin-induced renal dysfunction in rats. Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-pro-oxidant balance for preservation of the cell redox state by increasing antioxidant endogenous systems in various in vivo and in vitro experimental models.
To analyze the protective role of ozone oxidative preconditioning against cisplatin-induced nephrotoxicity.
Male Sprague-Dawley rats were pretreated with 15 intrarectal applications of ozone/oxygen mixture at 0.36, 0.72, 1.1, 1.8 and 2.5 mg/kg before cisplatin intraperitoneal injection (6 mg/kg). Serum and kidneys were extracted and analyzed 5 days after cisplatin treatment for determinations of the renal content of glutathione, thiobarbituric acid-reactive substances, renal concentration and enzymatic activities of catalase, superoxide dismutase and glutathione peroxidase.
Ozone pretreatment prevented the increase in serum creatinine levels, the glutathione depletion and the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. Also, the renal content of thiobarbituric acid-reactive substances was decreased by ozone therapy. These protective effects of ozone were dose dependent.
Intrarectal ozone therapy prevented effectively the renal antioxidant unbalance induced by cisplatin treatment.
Mediators of Inflammation 03/2004; 13(1):13-9. · 3.26 Impact Factor
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ABSTRACT: Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-prooxidant balance for preservation of the cell redox state by increasing antioxidant endogenous systems in both in vivo and in vitro experimental models. The aim of this study was to analyze the effect of ozone oxidative preconditioning on the level of tumor necrosis factor-alpha (TNF-alpha) in the serum of mice treated with lipopolysaccaride (LPS). Pretreatment with an ozone/oxygen gaseous mixture was administered intraperitoneally (0.2, 0.4 and 1.2 mg/kg) or by rectal application (0.2 and 0.4 mg/kg) once daily during five days before LPS (0.1 mg/kg, intraperitoneal). TNF-alpha was measured by cytotoxicity on L-929 cells. One hour after LPS injection, a significant mean increase of TNF-alpha in mouse serum was observed. Ozone/oxygen gaseous mixture reduced serum TNF-alpha levels in a dose-dependent manner. Statistically significant decreases in TNF-alpha levels after LPS injection were observed either with ozone intraperitoneal applications at 0.2 (78 %), 0.4 (98.5 %) and 1.2 (98.6 %) mg/ kg or by rectal application at 0.2 (46.2 %) and 0.4 (97.4 %) mg/kg. These results indicate that ozone oxidative preconditioning inhibits TNF-alpha production.
Arzneimittel-Forschung 02/2004; 54(12):906-9. · 0.72 Impact Factor
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ABSTRACT: It has been demonstrated that ozone, probably through a mechanism of oxidative preconditioning (OP), protected the liver against the damage mediated by reactive oxygen species. Taking into account that iscehmic preconditioning (IschP) is also a protective mechanism, a comparative study between both preconditioning settings was performed in order to study the effectiveness of both protective procedures. Rats were randomly divided into 4 groups: 1- control, sham operated (anesthesia and laparotomy plus surgical manipulation); 2- I/R (ischemia for 90 min followed by 90 min reperfusion); 3- Ischp+I/R, as group 2 but submitted to a previous ischemic preconditioning (ischemia 10 min and reperfusion 10 min); 4- OzoneOP+I/R, as group 2 but submitted to a pervious oxidative preconditioning with 15 sessions, daily, of ozone by rectal administration (dose of 1 mg/kg). The comparison between both preconditionings showed no biochemical differences for the parameters evaluated. Nevertheless, the histological study demonstrated that the protective effect produced by the OzoneOP is superior to that achieved with the IschP.
Ozone Science and Engineering 06/2003; 25(3):241-250. · 1.15 Impact Factor
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ABSTRACT: Many studies indicate that oxygen free-radical formation after reoxygenation of liver may initiate the cascade of hepatocellular injury. It has been demonstrated that controlled ozone administration may promote an oxidative preconditioning or adaptation to oxidative stress, preventing the damage induced by reactive oxygen species (ROS) and protecting against liver ischaemia-reperfusion (I/R) injury. On the basis of those results we postulated that ozone treatment in our experimental conditions has biochemical parameters similar to the ischaemic preconditioning (IscheP) mechanism. Four groups of rats were classified as follows: (1) sham-operated animals subjected to anaesthesia and laparotomy, plus surgical manipulation; (2) I/R animals were subjected to 90 min of right-lobe hepatic ischaemia, followed by 90 min of reperfusion; (3) IscheP, previous to the I/R period (as in group 2): animals were subjected to 10 min of ischaemia and 10 min of reperfusion; (4) ozone oxidative preconditioning (OzoneOP), previous to the I/R period (as in group 2): animals were treated with ozone by rectal insufflation 1 mg kg (-1). The rats received 15 ozone treatments, one per day, of 5-5.5 ml at the ozone concentration of 50 microg ml (-1). The following parameters were measured: serum transaminases (AST, ALT) and 5'-nucleotidase (5 '-NT), with morphological determinations, as indicators or hepatocellular injury; total sulfhydryl groups, calcium levels and calpain activity as mediators which take part in xanthine deshydrogenase (XDH) conversion to xanthine oxidase (XO) (reversible and irreversible forms, respectively); XO activities and malondialdehyde + 4-hydroyalkenals as indicators of increased oxidative stress. AST, ALT levels were attenuated in the IscheP (130 +/- 11.4 and 75 +/- 5.7 U l (-1)) with regard to the I/R group (200 +/- 22 and 117 +/- 21.7 U l (-1)) while the OzoneOP maintained both of the enzyme activities ( 89.5 +/- 12.6 and 43.7 +/- 10 U l (-1)) without statistical differences (P< 0.05) in comparison with the sham-operated ( 63.95 +/- 11 and 19.48 +/- 3.2 U l (-1)). Protective effects of both the preconditioning settings on the preservation of total sylfhydryl groups (IscheP: 6.28 +/- 0.07, OzoneOP: 6.34 +/- 0.07 micromol mg prot (-1)), calcium concentrations (IscheP: 0.18 +/- 0.09, OzoneOP: 0.20 +/- 0.06 micromol mg prot (-1)), and calpain activity (IscheP: 1.04 +/- 0.58, OzoneOP: 1.41 +/- 0.79 U mg prot (-1)) were observed. Both of the preconditionings attenuated the increase of total XO associated to I/R injury. Generation of malondialdehyde + 4 hydroxyalkenals was prevented by IscheP and OzoneOP without statistical differences between the two protective procedures. These results provide evidence that both of the preconditioning settings share similar biochemical mechanisms of protection in the parameters which were measured. Although there were no differences from a biochemical point of view between Ischaemic and OzoneOPs, the histological results showed a more effective protection of OzoneOP than IscheP in our experimental conditions.
Pharmacological Research 04/2002; 45(4):333-9. · 4.44 Impact Factor
