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- ItemSomente MetadadadosCaracteristicas clínicas e biomarcadores da perda auditiva sensorioneural súbita: papel no prognóstico(Universidade Federal de São Paulo (UNIFESP), 2021) Elias, Thais Gomes Abrahao [UNIFESP]; Penido, Norma De Oliveira [UNIFESP]; Universidade Federal de São PauloIntroduction: Sudden sensorineural hearing loss (SSHL) is a heterogeneous inflammatory disease, involving multiple causes and different inflammatory responses. We need to incorporate the concept of individualization and better classification of patients with SSHL, aiming to establish the endotypes of this pathology, offer the best therapeutic modality and be able to predict the hearing recovery and therapeutic response of each patient. Objective: To investigate the clinical and molecular characteristics and prognosis of hearing recovery in patients with sudden sensorineural hearing loss. Methods: A multicenter study was carried out, including patients diagnosed with SSHL from the Universidade Federal de São Paulo and Massachusetts Eye and Ear, Harvard Medical School, to compare clinical and molecular characteristics (Interleukin-6, Interleukin-10, Tumor-Necrosis Factor-Alpha, antioxidant enzymes and malondialdehyde activity). Results: It was possible to identify the etiology of SSHL in 45.6% of patients with unilateral SSHL (USSHL), 22.7% of patients with bilateral SSHL (BSSHL) non-simultaneous or sequential and 88.8% of patients with BSSHL simultaneous. 77.8% of patients with BSSHL simultaneous had severe or profound hearing loss even after treatment. The differences in the prevalence of severe to profound hearing loss in BSSHL simultaneous compared to unilateral USSHL and BSSHL non-simultaneous or sequential were statistically significant (P = 0.002). No statistically significant association was found between the concentration of interleukins, TNF-alpha, antioxidant enzymes and MDA and hearing recovery among patients with SSHL. As for the performance of patients with SSHL after cochlear implant surgery, there was also no statistically significant difference when compared with a group of patients with idiopathic bilateral sensorineural hearing loss. Discussion: It can be suggested that the involvement of the inner ear is worse in BSSHL simultaneous and is probably related to systemic diseases, mainly autoimmune diseases. The plasma concentration of cytokines and oxidative stress activity do not reliably represent possible elevations of these inflammatory products in the intracochlear environment, which is inaccessible for clinical studies to date. Patients with SSHL experience significant performance improvement after cochlear implant surgery regardless of the etiology of hearing loss. Conclusion: Simultaneous BSSHL should be considered as a distinct clinical entity, when compared to unilateral SSHL and nonsimultaneous or sequential BSSHL, with greater involvement of the inner ear and greater chance of having a worse recovery from hearing loss. We found no difference between hearing gain after cochlear implant surgery in patients with SSHL and patients with idiopathic progressive hearing loss. The plasma concentration of IL-6, IL-10, TNF-alpha, oxidative stress activity and concentrations of TBARS (MDA activity) and TLR 4 do not correlate with the prognosis of hearing recovery after SSHL.
- ItemSomente MetadadadosEfeito de uma dieta obesogênica, do treinamento aeróbio e dos níveis de estradiol no estado redox do músculo esquelético de ratas Wistar(Universidade Federal de São Paulo (UNIFESP), 2020-05-21) Santos, David Pedro Dos [UNIFESP]; Lambertucci, Rafael Herling [UNIFESP]; Universidade Federal de São PauloIntroduction: Obesity can lead to adipose tissue remodeling, changing its structure and composition. This phenomenon generates a systemic pro-inflammatory state associated with oxidative stress, which leads to muscle damage and metabolic dysfunctions. Physical activity positively modulates the antioxidant system against such disturbances. Evidence shows that estradiol, due to its antioxidant action, can protect the body from such aggressions. Objective: Evaluate how estradiol levels can modulate skeletal muscle’s redox state of Wistar rats submitted to a high fat diet and aerobic training. Materials and Methods: 40 female adult Wistar rats were used. The estrous cycle was monitored by analyzing vaginal smears. Among 80 rats, which were divided by quartiles considering the observed estradiol concentration, we used the animals that were in the first (Q1) and third (Q3) quartiles, thus totaling 40 rats. After the adaptation period, the rats were divided into 4 groups (n = 10) according to the diet offered and the performance or not of exercises, which: CS - received a control diet and remained sedentary; CT - received a control diet and performed physical training; HS - received a palatable high-fat diet and remained sedentary; HT - received a palatable high-fat diet and underwent physical training. We performed statistical analysis using the Generalized Linear Model and Fisher's post-test. Results: With the exception of the sedentary group fed with control diet, all groups with high estradiol showed higher total antioxidant status (TAS), at the same time, the groups with high estradiol had higher values of total oxidative status (TOS). The sedentary group with a high-fat diet and high estradiol had a lower oxidative stress index (OSI), compared to the trained group with a high-fat diet and low estradiol. Other than the sedentary group with a high-fat diet, all groups with high estradiol had higher values for the determination of lipid peroxidation (TBARS). The groups with high estradiol had a higher concentration of carbonylated protein. Except for the sedentary group with a control diet, all other groups with high estradiol showed higher nitric oxide values. Sedentary animals with high estradiol fed a high-fat diet had a higher catalase enzimatic activity when compared to animals with low estradiol Regarding the superoxide dismutase enzyme (SOD), all variables showed statistically significant difference, being: estradiol levels (χ2 = 21.346, p <0.001), training (χ2 = 21.004, p <0.001) and diet (χ2 = 4.644, p = 0.031), in addition to the interaction between estradiol levels with training (χ2 = 11.904, p <0.001), and estradiol levels with diet (χ2 = 8.668, p <0.003). For the group trained with a high-fat diet and a high level of estradiol, the value of glutathione peroxidase (GPX) activity was higher. Conclusion: Estradiol levels can interfere with the oxidative stress modulatory process and physical training can control it and improve the antioxidant profile. Regardless of estradiol levels, we observed that the isolated high-fat diet did not induce oxidative stress.
- ItemAcesso aberto (Open Access)Efeitos da suplementação com vitamina C na performance física: Uma revisão da literatura(Universidade Federal de São Paulo, 2022-08-15) Braga, Juliana Ferreira [UNIFESP]; Lambertucci, Rafael Herling [UNIFESP]; http://lattes.cnpq.br/5826005580515987; http://lattes.cnpq.br/4545649841501787; Universidade Federal de São Paulo (UNIFESP)O aumento do consumo de oxigênio, como prática frequente de exercício físico vigoroso resulta em estresse oxidativo, aumentando a síntese de espécies reativas de oxigênio (EROs). A suplementação com antioxidantes a vitamina C, por exemplo, é necessária quando os próprios mecanismos do organismo não conseguem suprir o aumento de espécies reativas de oxigênio (EROs), aumentando o estresse oxidativo gerado pelo exercício. O presente estudo tem como objetivo, através de uma revisão de literatura, analisar os efeitos da suplementação de vitamina C na performance física de atletas. O método consiste em realizar uma busca na base de dados disponível na literatura utilizando trabalhos em inglês e português, referente a suplementação de vitamina C e seus resultados na performance física, e assim, efetuar uma análise dos dados por meio da leitura dos trabalhos selecionados de forma independente, desconsiderando o ano de publicação dos trabalhos. A partir dos estudos revisados, foi demonstrado que mais pesquisas são necessárias para elucidar esse tema, pois os resultados obtidos não foram esclarecedores referente a suplementação com vitamina C na performance física.
- ItemAcesso aberto (Open Access)Estudo da sinalização glutamatérgica, estresse oxidativo e morte celular em cérebros de ratos durante o envelhecimento(Universidade Federal de São Paulo (UNIFESP), 2008-06-25) Ureshino, Rodrigo Portes [UNIFESP]; Smaili, Soraya Soubhi [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)O envelhecimento é um processo multi-fatorial associado a déficits funcionais, sendo que o cérebro é um dos órgãos com maior susceptibilidade a doenças crônico-degenerativas. Dentre essas, as doenças de Alzheimer e de Parkinson apresentam maior prevalência na população global e levam à incapacitação severa do indivíduo. Assim, o entendimento dos mecanismos dessas doenças que estão relacionados com o envelhecimento é importante para a busca de alternativas de tratamento. Há evidências de que, em doenças neurodegenerativas, ocorrem alterações na homeostase do cálcio (Ca2+), o que pode contribuir para a morte celular por apoptose. No presente trabalho, buscamos investigar fenômenos envolvidos com a tríade Ca2+ -mitocondria- EROs (espécies reativas do oxigênio) (TOESCU, 2005) e a apoptose em corpo estriado de ratos no envelhecimento. Foram avaliadas a sinalização intracelular dinâmica (em tempo real) e estática (biologia molecular), a morfologia celular e ultraestrutural, a morfometria e bioenergética. Utilizando fatias cerebrais de ratos, observamos que os anmais senescentes apresentaram um aumento de Ca2+ citosólico maior que os animais jovens, após a estimulação glutamatérgica. Em seguida, utilizamos antagonistas parciais das duas classes de receptores, os metabotrópicos do grupo I e os ionotrópicos (NMDAR), para estudar os componentes desse aumento de Ca2+. Avaliamos também o aumento de Ca2+ citosólico mediado por agentes que mobilizam esse íon do retículo endoplasmático e da mitocôndria, mostrando que esses estoques de Ca2+ podem estar aumentados no envelhecimento. As medidas do ∆ψm basal mostraram que hei urna diminuição deste parâmetro no envelhecimento, sendo estas alterações condizentes com a inibição mais acentuada do complexo I da cadeia transportadora de elétrons e do aumento na produção de EROs. As alterações funcionais não implicaram em mudanças ultraestruturais da mitocôndria. Foram investigados a expressão gênica e o conteúdo proteíco de Bax e Bcl-2, mostrando um aumento da expressão de bax e uma redução de proteínas Bcl-2, o que pode ter uma relação com o aumento de apoptose encontrado no estriado dos animais senescentes. Desse modo, os resultados indicam que, no envelhecimento, existem alterações no controle intracelular de sinalização de Ca2+ e na bioenergética, que podem contribuir para o aumento de apoptose.
- ItemAcesso aberto (Open Access)FTY720 induces apoptosis in B16F10-NEX2 murine melanoma cells, limits metastatic development in vivo, and modulates the immune system(Faculdade de Medicina / USP, 2013-07-01) Pereira, Felipe Valença [UNIFESP]; Arruda, Denise Costa [UNIFESP]; Figueiredo, Carlos Rogerio [UNIFESP]; Massaoka, Mariana Hiromi [UNIFESP]; Matsuo, Alisson Leonardo [UNIFESP]; Bueno, Valquiria [UNIFESP]; Rodrigues, Elaine Guadelupe [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)OBJECTIVE: Available chemotherapy presents poor control over the development of metastatic melanoma. FTY720 is a compound already approved by the Food and Drug Administration for the treatment of patients with multiple sclerosis. It has also been observed that FTY720 inhibits tumor growth in vivo (experimental models) and in vitro (animal and human tumor cells). The aim of this study was to evaluate the effects of FTY720 on a metastatic melanoma model and in tumor cell lines. METHODS: We analyzed FTY720 efficacy in vivo in a syngeneic murine metastatic melanoma model, in which we injected tumor cells intravenously into C57BL/6 mice and then treated the mice orally with the compound for 7 days. We also treated mice and human tumor cell lines with FTY720 in vitro, and cell viability and death pathways were analyzed. RESULTS: FTY720 treatment limited metastatic melanoma growth in vivo and promoted a dose-dependent decrease in the viability of murine and human tumor cells in vitro. Melanoma cells treated with FTY720 exhibited characteristics of programmed cell death, reactive oxygen species generation, and increased β-catenin expression. In addition, FTY720 treatment resulted in an immunomodulatory effect in vivo by decreasing the percentage of Foxp3+ cells, without interfering with CD8+ T cells or lymphocyte-producing interferon-gamma. CONCLUSION: Further studies are needed using FTY720 as a monotherapy or in combined therapy, as different types of cancer cells would require a variety of signaling pathways to be extinguished.
- ItemAcesso aberto (Open Access)Oxigenação hiperbárica melhora o controle redox e reduz a mortalidade na fase aguda do infarto do miocárdio em rato(Universidade Federal de São Paulo (UNIFESP), 2021) Oliveira, Mario Sergio De [UNIFESP]; Tucci, Paulo Jose Ferreira [UNIFESP]; Universidade Federal de São PauloIntroduction The potential of hyperbaric oxygenation to reduce cardiac lesions via redox homeostasis raises the possibility of extending the viability period of the at-risk myocardium. This circumstance is beneficial for late ischemic area reperfusion interventions. Aim The present study analyzed the changes in the redox system triggered by hyperbaric oxygenation therapy during acute myocardial infarction in rats. Material and methods Male Wistar EPM rats, weighing between 250 to 330 g (11-12 weeks of age) were used in the study. The rats (n = 138) were randomly separated into one of the following experimental groups: Sham (SH = 26), myocardial infarction (MI = 72), and infarction plus hyperbaric therapy (HBO = 40). The HBO therapy was carried out for 60 minutes on 2.5 absolute atmospheres. Heart samples were collected after 90 minutes of coronary occlusion and in a similar period for the SH group. Assays were performed to determine the total levels of superoxide dismutase, catalase, peroxiredoxin, and 3-nitrotyrosine proteins.Glutathione level was measured by indirect enzyme immunoassay. Superoxide anion was detected by the oxidation of dihydroethide on confocal microscopy. Nitrite and nitrate levels were evaluated by chemiluminiscence. Data are presented as mean + standard error of mean. Parametric data were analyzed with two-way ANOVA and Newman-Keuls post test. Kruskal-Wallis and Dunn’s post-test were applied to nonparametric data. The level of significance was set at p<0.05. Results Mortality was significantly higher in the MI group (37.5%) compared to the HBO group (15%). The infarction size was not significantly different between the HBO (38 ± 2.0%) and MI groups (43 ± 2.5%). Oxidized/reduced glutathione ratio (SH = 30+4; IM = 17+3; HBO = 10+1) and peroxiredoxin levels (SH = 1.45+0.26; MI = 1.24+0.18; HBO = 0.65+0.05; AU/ μg) were significantly higher in the SH and MI groups when compared to the HBO group. A significantly higher contente of superoxide dismutase (SH = xv 0.69+0.08; MI = 0.79+0.04; HBO = 1+0.06; AU/μg) and catalase (SH = 0.66+0.04; IM = 0.73+0.07; HBO = 0.97+0.06; AU/μg) was found in the HBO group compared to SH and MI groups. The 3-Nitrotyrosine (SH = 3.36+0.20; MI = 3.08+0.16; HBO = 2.40+0.18; AU) and superoxide radical (SH = 1.40+0.11; MI = 1.87+0.08; HBO = 0.86+0.08, AU) levels were significantly lower in the HBO group compared to the MI and SH groups. Conclusion The HBO therapy decreased mortality and improved redox control in the heart of rats in the acute phase of myocardial infarction.