RESUMO
The current treatment of leishmaniasis presents some problems, such as cell toxicity, parenteral route, and time of treatment. Ozone emerges as an option to accelerate the standard treatment due to the immunomodulatory, antioxidant, and wound healing activity reported in the literature. This work aimed to evaluate the efficacy of aqueous ozone as an adjuvant to the standard treatment of cutaneous lesions caused by Leishmania amazonensis in an experimental model. For in vivo experiments, mice were randomly distributed in 6 groups, which were infected with L. amazonensis and treated in five different schedules using the standard treatment with Glucantime® with or without aqueous ozone. After the last day of treatment, the animals were euthanized and were analyzed: the thickness of lesions; collagen deposition, the parasitic burden of the lesions; blood leukocyte number; NO; and cytokine dosages and arginase activity from peritoneal macrophages. All treated groups showed a decrease in the lesion, but with a significative deposition of collagen in lesions with local ozone treatment. The parasite burden showed that ozone enhanced the leishmanicidal activity of the reference drug. The reduction of NO production and blood leukocyte count and increases in the arginase activity showed an immunomodulatory activity of ozone in the treated animals. Thus, ozone therapy has been shown to work as an adjuvant in the treatment of Leishmania lesions, enhancing leishmanicidal and wound healing activity of standard treatment.
Assuntos
Leishmaniose/tratamento farmacológico , Oxidantes Fotoquímicos/administração & dosagem , Ozônio/administração & dosagem , Animais , Feminino , Imunomodulação , Leishmania mexicana/efeitos dos fármacos , Leishmaniose/imunologia , Leishmaniose/parasitologia , Leishmaniose/patologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Antimoniato de Meglumina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Resultado do Tratamento , Cicatrização/efeitos dos fármacosRESUMO
To verify the influence of ozone (O3) therapy on an experimental model of rheumatoid arthritis (RA), 30 male Wistar rats were randomly allocated to 2 groups, control (C) and treatment (T), and subdivided into control (C12, C48, C72) and treatment (T12, T48, T72) groups. RA was induced by administration of collagenase plus complete Freud's adjuvant in the knee joint region. The animals were treated with ozone therapy (1 ml O3 injection in the knee i.a.) according to group assignment: T12, 2 h; T48, 2 and 24 h; and T72, 2, 24, and 48 h post-RA induction. The different animal groups were euthanized 12, 24, or 72 h post-RA induction, respectively. Synovial exudate levels of IL-10, IL-12p70, TNF-α, INF-γ, and MCP-1 were assessed by flow cytometry, and histopathological analysis of the knee cartilage was conducted. Ozone therapy effectively decreases inflammation, reducing IL-12 and TNF-α, and increasing IL10. O3 did not statistically affect INF-γ or MCP-1 levels. More expressive results were obtained with group T72, i.e., treated 2, 24, and 48 h post-RA induction, which indicates that longer-term ozone treatment is more effective than a single acute application. Ozone therapy effectively reduced inflammation with effects, at least in part, mediated through reduction of pro-inflammatory cytokines and activation of IL-10 anti-inflammatory cytokine.
Assuntos
Anti-Inflamatórios/administração & dosagem , Artrite Experimental/metabolismo , Artrite Experimental/terapia , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Ozônio/administração & dosagem , Animais , Artrite Experimental/induzido quimicamente , Modelos Animais de Doenças , Adjuvante de Freund/toxicidade , Masculino , Oxidantes Fotoquímicos/administração & dosagem , Ratos , Ratos WistarRESUMO
PURPOSE:: To assess and compare the histopathological effects of ozone therapy and/or methylprednisolone (MPS) treatment on regeneration after crush type sciatic nerve injury. METHODS:: Forty Sprague-Dawley male rats were randomly allocated into four groups. Four groups received the following regimens intraperitoneally every day for 14 days after formation of crush type injury on sciatic nerve: Group I: ozone (20mcg/ml); Group II: methylprednisolone (2mg/kg); Group III: ozone (20 mcg/ml) and methylprednisolone (2mg/kg); Group IV: isotonic saline (0.9%). The histomorphological evaluation was made after biopsies were obtained from the sites of injury. RESULTS:: Significant differences were noted between groups in terms of degeneration (p=0.019), nerve sheath cell atrophy (p=0.012), intraneural inflammatory cellular infiltration (p=0.002), perineural granulation tissue formation (p=0.019), perineural vascular proliferation (p=0.004), perineural inflammatory cellular infiltration (p<0.001) and inflammation in peripheral tissue (p=0.006). Degeneration was remarkably low in Group III, while no change in nerve sheath cell was noted in Group II. CONCLUSION:: The combined use of methylprednisolone and ozone treatment can have beneficial effects for regeneration after crush type nerve injury.
Assuntos
Metilprednisolona/uso terapêutico , Regeneração Nervosa/efeitos dos fármacos , Oxidantes Fotoquímicos/uso terapêutico , Ozônio/uso terapêutico , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia , Animais , Inflamação , Masculino , Metilprednisolona/administração & dosagem , Compressão Nervosa , Oxidantes Fotoquímicos/administração & dosagem , Ozônio/administração & dosagem , Traumatismos dos Nervos Periféricos/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Cicatrização/efeitos dos fármacosRESUMO
ABSTRACT PURPOSE: To assess and compare the histopathological effects of ozone therapy and/or methylprednisolone (MPS) treatment on regeneration after crush type sciatic nerve injury. METHODS: Forty Sprague-Dawley male rats were randomly allocated into four groups. Four groups received the following regimens intraperitoneally every day for 14 days after formation of crush type injury on sciatic nerve: Group I: ozone (20mcg/ml); Group II: methylprednisolone (2mg/kg); Group III: ozone (20 mcg/ml) and methylprednisolone (2mg/kg); Group IV: isotonic saline (0.9%). The histomorphological evaluation was made after biopsies were obtained from the sites of injury. RESULTS: Significant differences were noted between groups in terms of degeneration (p=0.019), nerve sheath cell atrophy (p=0.012), intraneural inflammatory cellular infiltration (p=0.002), perineural granulation tissue formation (p=0.019), perineural vascular proliferation (p=0.004), perineural inflammatory cellular infiltration (p<0.001) and inflammation in peripheral tissue (p=0.006). Degeneration was remarkably low in Group III, while no change in nerve sheath cell was noted in Group II. CONCLUSION: The combined use of methylprednisolone and ozone treatment can have beneficial effects for regeneration after crush type nerve injury.
Assuntos
Animais , Masculino , Ratos , Oxidantes Fotoquímicos/uso terapêutico , Ozônio/uso terapêutico , Nervo Isquiático/lesões , Metilprednisolona/uso terapêutico , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Regeneração Nervosa/efeitos dos fármacos , Oxidantes Fotoquímicos/administração & dosagem , Ozônio/administração & dosagem , Nervo Isquiático/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Metilprednisolona/administração & dosagem , Distribuição Aleatória , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/fisiopatologia , Inflamação , Compressão NervosaRESUMO
BACKGROUND: Ozone therapy may stimulate antioxidant systems and protect against free radicals. It has not been used formerly in patients with pulmonary emphysema. AIM: To assess the effects of rectal ozone therapy in patients with pulmonary emphysema. MATERIAL AND METHODS: Sixty four patients with pulmonary emphysema, aged between 40 and 69 years, were randomly assigned to receive rectal ozone in 20 daily sessions, rectal medicinal oxygen or no treatment. Treatments were repeated three months later in the first two groups. At baseline and at the end of the study, spirometry and a clinical assessment were performed. RESULTS: fifty patients completed the protocol, 20 receiving ozone therapy, 20 receiving rectal oxygen and 10 not receiving any therapy. At baseline, patients on ozone therapy had significantly lower values of forced expiratory volume in the first second (fEV1) and fEV1/forced vital capacity. At the end of the treatment period, these parameters were similar in the three treatment groups, therefore they only improved significantly in the group on ozone therapy. No differences were observed in other spirometric parameters. CONCLUSIONS: Rectal ozone therapy may be useful in patients with pulmonary emphysema.
Assuntos
Oxidantes Fotoquímicos/administração & dosagem , Oxigênio/administração & dosagem , Ozônio/administração & dosagem , Enfisema Pulmonar/terapia , Administração Retal , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enfisema Pulmonar/fisiopatologia , Testes de Função Respiratória , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Background: Ozone therapy may stimulate antioxidant systems and protect against free radicals. It has not been used formerly in patients with pulmonary emphysema. Aim: To assess the effects of rectal ozone therapy in patients with pul-monary emphysema. Material and Methods: Sixty four patients with pulmonary emphysema, aged between 40 and 69 years, were randomly assigned to receive rectal ozone in 20 daily sessions, rectal medicinal oxygen or no treatment. Treatments were repeated three months later in the frst two groups. At baseline and at the end of the study, spirometry and a clinical assessment were performed. Results: fifty patients completed the protocol, 20 receiving ozone therapy, 20 receiving rectal oxygen and 10 not receiving any therapy. At baseline, patients on ozone therapy had significantly lower values of forced expiratory volume in the frst second (fEV1) and fEV1/forced vital capacity. At the end of the treatment period, these parameters were similar in the three treatment groups, therefore they only improved significantly in the group on ozone therapy. No differences were observed in other spirometric parameters. Conclusions: Rectal ozone therapy may be useful in patients with pulmonary emphysema.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxidantes Fotoquímicos/administração & dosagem , Oxigênio/administração & dosagem , Ozônio/administração & dosagem , Enfisema Pulmonar/terapia , Administração Retal , Método Duplo-Cego , Enfisema Pulmonar/fisiopatologia , Testes de Função Respiratória , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
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.
Assuntos
Antibacterianos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Pé Diabético/tratamento farmacológico , Oxidantes Fotoquímicos/uso terapêutico , Ozônio/uso terapêutico , Cicatrização/efeitos dos fármacos , Adulto , Idoso , Antibacterianos/administração & dosagem , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Pé Diabético/patologia , Pé Diabético/fisiopatologia , Feminino , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oxidantes Fotoquímicos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ozônio/administração & dosagemRESUMO
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.
Assuntos
Antioxidantes/metabolismo , Taxa de Filtração Glomerular , Falência Renal Crônica/urina , Oxidantes Fotoquímicos/administração & dosagem , Ozônio/administração & dosagem , Animais , Feminino , Rim/irrigação sanguínea , Rim/metabolismo , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/fisiopatologia , Modelos Animais , Nefrectomia , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Potássio/urina , Ratos , Ratos Wistar , Sódio/urinaRESUMO
BACKGROUND: 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 and protecting against liver ischaemia-reperfusion (I/R) injury. AIMS: In the present study, the effects of ozone oxidative preconditioning (OzoneOP) on nitric oxide (NO) generation and the cellular redox balance have been studied. METHODS: Six groups of rats were classified as follows: (1). sham-operated; (2). sham-operated+l-NAME (N(omega)-nitro-l-arginine methyl ester); (3). I/R (ischaemia 90 min-reperfusion 90 min); (4). OzoneOP+I/R; (5). OzoneOP+l-NAME+I/R; and (6). l-NAME+I/R. The following parameters were measured: plasma transaminases (aspartate aminotransferase, alanine aminotransferase) as an index of hepatocellular injury; in homogenates of hepatic tissue: nitrate/nitrite as an index of NO production; superoxide dismutase (SOD), catalase (CAT) and glutathione levels as markers of endogenous antioxidant system; and finally malondialdehyde+4-hydroxyalkenals (MDA+4-HDA) and total hydroperoxides (TH) as indicators of oxidative stress. RESULTS: A correspondence between liver damage and the increase of NO, CAT, TH, glutathione and MDA+4-HDA concentrations were observed just as a decrease of SOD activity. OzoneOP prevented and attenuated hepatic damage in I/R and OzoneOP+l-NAME+I/R, respectively, in close relation with the above-mentioned parameters. CONCLUSIONS: These results show that OzoneOP protected against liver I/R injury through mechanisms that promote a regulation of endogenous NO concentrations and maintenance of cellular redox balance. Ozone treatment may have important clinical implications, particularly in view of the increasing hepatic transplantation programs.