Navegando por Palavras-chave "Espécies Reativas De Oxigênio"
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- ItemSomente MetadadadosAvaliação da produção de espécies reativas de oxigênio em ilhotas pancreáticas de camundongos knockout para o receptor Toll-4 (TLR4)(Universidade Federal de São Paulo (UNIFESP), 2019-05-30) Pereira, Ana Cristina Vieira [UNIFESP]; Hirata, Aparecida Emiko [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Toll-like receptors (TLRs)-like part of the innate immune system and seem to be involved in the modulation of several metabolic chronic diseases such as obesity and type 2 diabetes (DM2). Is sábido to chronic Hyperglycemia is associated with increased generation of EROs in the pancreatic islets, and this interferes with the insulin secretory process. Studies show that the delection of TLR4 receptors improves insulin resistance and chronic diseases such as obesity and type 2 diabetes (DM2). Thus, the aim of this study is to evaluate the regulation of ROS generation, in isolated pancreatic islets from KNOCKOUT mice for the receptor TLR4 (TLR4-/-), in different concentrations of glucose and/or mix of cytokines. TLR4-/- mice showed significant decrease in blood glucose levels while showed increased insulinemia compared to controls. We also observed significant increase in the relative weight of the skeletal muscle. The superoxide generation, evaluated by flow cytometry, was significantly lower compared to the control group. There were no changes in the mitochondrial superoxide and hydrogen peroxide generation. ROS geneartion stimulated by cytokines was not observed in TLR4-/- animals. The protein expression of JNK and IKKB, evaluated by Western blotting, was significantly lower in skeletal muscle of TLR4-/- animals compared to controls. However, we observed a significant increase in the protein expression of NRF2 in skeletal muscle of TLR4-/- animals comparte to controls. These results demonstrate that TLR4 participates in the redox state of the pancreatic islets, which could at least partly influence the secretory process of insulin. This mechanism appears to be mediated via JNK/IKKB and NRF2.
- 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 MetadadadosCaracterização da TCCYP19 e o estudo do seu papel durante a infecção celular causada pelo Trypanosoma cruzi(Universidade Federal de São Paulo (UNIFESP), 2020-12-18) Santos, Gregory Pedroso Dos [UNIFESP]; Schenkman, Sergio [UNIFESP]; Universidade Federal de São PauloChagas disease caused by the protozoan parasite Trypanosoma cruzi is characterized by an extensive inflammatory process in the organs and sites most affected by the infection. To understand the evasion mechanisms developed by the parasite in response to attempts to control the infection by the host organism - several studies have being published describing an intriguing relationship between reactive oxygen species (ROS) produced by infected cells, and their ability to induce or increase in the proliferation of T. cruzi. So far, the mechanisms involved in these processes are still unknown. However, these studies suggested that parasites have developed a mechanism to deal with oxidative stress, which nullifies the antimicrobial capacity, or which is capable of converting these oxidative environments to their benefit. In this thesis, we studied a chaperone of 19 kDa, expressed by T. cruzi, entitled cyclophilin 19 (TcCyp19), that has high similarity to cyclophilin A (CypA), expressed by mammals. CypA acts in the activation of the cellular immune and inflammatory response, as well as in the translocation of the p47phox subunit - responsible for activation of the NADPH oxidase enzyme complex, which leads to the production reactive oxygen species. We found that TcCyp19 is expressed in all T. cruzi stages, being more abundant in the epimastigote form of the parasite. Through adaptations carried out by genetic engineering, we have generated parasites capable of expressing TcCyp19 fused to a HA tag. This approach allowed us to detect its secretion by the intracellular amastigote form in the cytosol of the host cell . Furthermore, we observed that modulations in the expression of TcCyp19, both in the parasite and through the expression carried out directly in the host cell, increased the intracellular multiplication capacity of the parasite concomitant with TcCyp19 release in the cytosol of infected cells. We also noticed a parallel increase in the production of ROS, during infections and when rat myoblast L6 cells expressed TcCyp19. In contrast, parasites depleted of TcCyp19 gene showed a substantial reduction in the intracellular amastigotes proliferation, similar to what was observed for wild type parasites treated with antioxidant enzymes or with a cyclosporine A (a specific inhibitor of cyclophilins). The knockout parasites also generated a significant reduction in the production of ROS in infected cells. Both reduced proliferation and low ROS production were reestablished by the add-back parasites or when infecting L6 cells that express the TcCyp19. Mechanistically, the production of ROS generated by TcCyp19 appears to be related to the activation of the NADPH oxidase by the translocation of the p47phox subunit to the cell surface as previously found for CypA. In fact, part of the TcCyp19 colocalize of stretches of p47phox aligned with microfilaments in L6 cells and concentrate in the leading edges of the cells in regions proposed to contain active NADPH oxidase. We conclude that TcCyp19 is a key molecule responsible for inducing increased production of ROS, which in turn can influence proliferation of parasites and guarantee the prevalence of infection.
- 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)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.