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- ItemSomente MetadadadosAvaliação do tratamento crônico com resveratrol sobre níveis glicêmicos e parâmetros reprodutivos de ratos com diabetes tipo 1 induzida pela estreptozotocina na pré-puberdade(Universidade Federal de São Paulo (UNIFESP), 2014-12-18) Simas, Joana Nogueres [UNIFESP]; Valdeolivas, Sandra Maria Miraglia Valdeolivas [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Aims/hypothesis: In Diabetes Mellitus, the persistent hyperglycemia unleashes the progression of several complications including the overproduction of reactive oxygen species and reproductive alterations. Resveratrol (RES) is antioxidant and antiapoptotic. We assessed the trilogy: type-1 Diabetes (DM1), male reproduction and RES-treatment. Methods: Eighty-four prepubertal male rats were distributed into 7 groups: sham-control (SC); RES-treated (R);resveratrol-vehicle-treated (RV); diabetic (D); diabetic-insulin-treated (DI); diabetic-RES-treated (DR), diabetic-insulin and RES-treated (DIR). DM1 was induced by a single intraperitoneal streptozotocin (STZ) injection (65 mg/kg) on the 30th day postpartum (dpp). Animals of DR, DIR and R groups received 150mg/day of RES by gavage for 42 consecutive days (from the 33 dpp). DI and DIR rats received subcutaneous injections of insulin (1U/100g bw/day) from the 5th day after the DM1 induction. The blood-glucose-measurement (BGM) of rats was obtained at 5 different time-points: before the STZ-treatment, at 33, 45, 64 and 75 dpp when they were submitted to euthanasia for morphometric and biometric testicular analyses, spermatic evaluation and hormonal dosages. Results: In the D group, BGM was higher than in DR, DI and DIR. Besides, morphometric testicular measurements and testosterone and estradiol dosages were lower than in DR and DIR; LH-dosage was also lower than in DR. The preputial-separation age was delayed in diabetes-induced groups. The DR and DIR groups showed an improvement of the sperm mitochondrial activity, epididymal sperm counts and of the frequency of morphologically normal sperms. Conclusions/interpretation: RES improved glycemia, sperm quantitative and qualitative parameters and hormonal profile in DM1-induced Rats.
- ItemSomente MetadadadosAvaliação morfofuncional e estresse oxidativo no intestino de camundongos distróficos (mdx)(Universidade Federal de São Paulo (UNIFESP), 2014-12-17) Alves, Gabriel Andrade [UNIFESP]; Nouailhetas, Viviane Louise Andree Nouailhetas [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Dystrophin is a component of the complex of dystrophin-associated proteins, which connects the cytoskeleton to the plasma membrane and the extracellular matrix. Their lack causes Duchenne Muscular Dystrophy (DMD), characterized by a progressive degeneration of skeletal and cardiac muscle, leading to death in patients third decade of life. Although DMD patients had gastrointestinal symptoms such as diarrhea and pseudo obstruction, little is known of the role of dystrophin in the intestinal smooth muscle (MLI). We aim to understand what is the role of dystrophin protein in MLI: structurally and functionally, muscle contraction. Specifically studied animal model (mdx mice), and assess the structure and ultrastructure of the ILM, the resistance loss of contractile response of the MLI exposed stretch, a loss of contractile response in medium without Ca2 + (essential for contraction) and recovery contractile respota with the replacement of the ion in the presence or absence of nifedipine (blocker Cav1.2b). Observe surprising resistance to loss of response during stretch despite the animal gut dystrophic have structural mucosal deficit and have demonstrated loss of muscle layer (30%) compared to the control, present degenerate mitochondria and sarcoplasmic reticulum change. The response in medium without calcium, dystrophic animals was more resistant both to the loss of contraction in medium without Ca2 +, as the recovery of contractility with replacement ion. Dystrophin has a peculiar role in MLI, different from that of skeletal muscle, because despite the visible structural deficit, there was an increase in resistance to loss of contractility stretch. The dystrophic mdx mice also presents kinetics in response to varying external impaired calcium concentration (thus probably with changes in Cav1.2b), which may help to understand symptoms present in DMD patients.
- ItemSomente MetadadadosBiomarcadores periféricos nos transtornos psicóticos: a influência de características clínicas, estágio da doença e tratamento(Universidade Federal de São Paulo (UNIFESP), 2015-10-16) Noto, Cristiano de Souza [UNIFESP]; Brietzke, Elisa Macedo Brietzke [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)INTRODUCTION: Schizophrenia is a chronic disease, with considerable impact on live of individuals and their families. Its origin is related to a complex interaction between genetic and environmental factors during brain development. Despite advances in research, there are no biological markers to confirm the diagnosis, indicate the prognosis, or assist in therapeutic decision. Changes in immune system and oxidation processes have been consistently associated with schizophrenia and markers of these processes emerge as promising biomarkers. However, the current literature is still heterogeneous, and the role of factors such as the use of medication or phenotypic variability remain a challenge to be surmounted. This thesis presents seven studies investigating biomarkers related to inflammation and oxidative stress in different aspects of the disorder. AIMS: To investigate psychotic disorders longitudinally, with a multi-phase and multimodal approach, taking into account clinical heterogeneity. Hence, it was explored the immunological profile and oxidative biomarkers, by evaluating different subgroups of the disease (first episode, drug-naïve patients, the presence of depression, before and after treatment, treatment-resistance). It was also evaluated the relationship between inflammation, oxidative and genetic biomarkers. METHODS: Patients were recruited in their first psychotic episode (FEP), drug-naïve, and followed for an average period of 8 weeks under risperidone. It was also evaluated patients in advanced stages, with more than 1 year of disease. Patients were diagnosed by SCID, with psychopathological evaluation by PANSS and CDSS. RESULTS: FEP patients have increased levels of interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-alpha when compared to healthy controls. They also have increased total reactive antioxidant potential (TRAP) and decreased activity of paraoxonase (PON) 1. Those in FEP with depression had higher levels of IL-4 and TNFalfa compared to those without depression, and increased expression of COMT and decrease expression NDEL1. After treatment with risperidone, the three mentioned cytokines, and additionally, IL-4 reduced significantly, and lipid hydroperoxides (LOOH) levels decreased and PON1 activity increased. Next, it was demonstrated that the combination of five biomarkers (sTNF-R1, sTNF-R2, CCL11, IP-10, IL-4) may predict the diagnosis of schizophrenia with a sensitivity of 70.0% and a specificity of 89 4%. Treatment resistance patients showed distinct inflammatory profile, with an increase in increased levels of sTNF-R1, sTNF-R2, and MCP-1. Finally, increased levels of IL-6 was associated with reduced expression of AKT1 and DROSHA, while an increase of IL-10 was associated with increased expression NDEL1, DISC1 and MBP. IL-6 also significantly increased expression of AKT1, DICER1, DROSHA and COMT induced by risperidone. DISCUSSION: It was shown that a disorder in the immune system and oxidative balance is already present from the onset of schizophrenia, before the use of antipsychotic drugs. Moreover, it was suggested that risperidone has antioxidative and anti-inflammatory effects. Features such as depression and treatment resistance also presented a specific immunological profile. Finally, it was showed that inflammatory cytokines play an important role in the regulation of oxidative processes and gene expression. Using an innovative approach and seeking for convergence between different methodologies, the results generated new perspectives in understanding the pathophysiological mechanisms underpinning the neurobiology of schizophrenia.
- ItemAcesso aberto (Open Access)Doença hepática gordurosa não alcoólica em escolares obesos(Sociedade de Pediatria de São Paulo, 2008-06-01) Souza, Fabíola Isabel S.; Amancio, Olga Maria Silverio [UNIFESP]; Sarni, Roseli Oselka Saccardo [UNIFESP]; Pitta, Tassiana Sacchi; Fernandes, Ana Paula; Fonseca, Fernando Luiz Affonso [UNIFESP]; Hix, Sonia; Universidade Federal de São Paulo (UNIFESP); Faculdade de Medicina do ABCOBJECTIVE: To evaluate the prevalence of altered hepatic ultrasound and elevated serum alanine aminotransferase (ALT) in overweight and obese children, as well as to relate them to lipid peroxidation, lipid profile and insulin resistance. METHODS: A prospective, controlled, cross-sectional study was performed with 67 overweight and obese children (38 female, mean age of 8,6 years) paired by gender and age with 65 eutrophic controls. The following parameters were evaluated: lipid profile (LDL-c, HDL-c, triglycerides), ALT, lipid peroxidation measured by thiobarbituric acid reaction substance (TBARS), serum glucose and insulin resistance (Homeostasis Model Assessment). Hepatic steatosis was evaluated by ultrasound by a single professional and classified as diffuse mild, moderate or severe. RESULTS: Elevated ALT (>40 U/L) was observed in 3% and altered ultrasound in 57.4% of the overweight/obese children. Obese/overweight children showed a higher percentage of ALT >18 U/L (OR 4.2, p=0.0006) and hypertriglyceridemia (OR 4.2, p<0.001). ALT was associated with elevated triglycerides (OR 3,2; p=0,010). There was not association between TBARS (oxidative stress) or HOMA-IR with the presence of overweight/obesity or ALT >18 U/L. CONCLUSIONS: The frequency of altered ALT (>40U/L) was low and of altered hepatic ultrasound was high. There was no association between fatty liver at ultrasound with nutritional status or ALT levels. Elevated triglycerides were associated with higher levels of ALT.
- ItemSomente MetadadadosEfeito da administração da n-acetilcisteína na reposição volêmica sobre a lesão renal induzida por choque hemorrágico em ratos(Universidade Federal de São Paulo (UNIFESP), 2014-08-27) Moreira, Miriam Aparecida [UNIFESP]; Martins, Jose Luiz Martins [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objective: To evaluate the effect of N-acetylcysteine on renal injury due to controlled hemorrhagic shock in rats. Method: hemorrhagic shock was induced in Wistar rats by withdrawing blood to reach mean arterial blood pressure to 35 ± 5 mmHg for 60 minutes blood. After this period, the animals were distributed randomly into two groups according to treatment: Ringer lactate group (RL), resuscitated with Ringer's lactate 33mL/Kg and N-acetylcysteine group (NAC), resuscitated with Ringer's lactate and 150mg/Kg of N-acetylcysteine and 50% of blood drawn for both groups. A third group of animals (control group) was submitted of catheterization procedure without inducing shock. After fluid resuscitation, the animals were observed for 120 minutes and euthanized. Results: NAC attenuated renal dysfunction, indicated by lower plasma creatinine in the group of animals treated with NAC compared to the RL group (0.39±0.1 vs 2.9±1.6 mg/dL, P<0.0001). The animals treated with NAC had less oxidative stress with lower values of TBARS tissue, nitric oxide and superoxide anion when compared with the RL group (0.60± 0.05 vs 1.3±0.2 nmol/mL protein,.184.7±20 vs 381.3±93 nM and 4.3±0.4 vs 18.2 ± 3.1%, P<0.0001, respectively) and apoptosis observed by the lower expression of Bax, cytochrome c and caspase 3 proteins in animals treated with NAC as compared to animals of RL group (0,9±0.06 vs 7.1±1.3; 0.3±0.3 vs 17.8±2.8; 3.8±0.4 vs. 10.0±1.5%, P<0.0001; respectively). NAC attenuated the morphological changes that were induced by the shock and larger diameter of the glomeruli when compared to the other two groups. Conclusion: NAC associated with fluid resuscitation attenuated renal injury in rats previously submitted to controlled hemorrhagic shock. NAC promotes improvement of morphological and functional changes and decreased oxidative stress and apoptosis of the kidney.
- ItemAcesso aberto (Open Access)Efeito do exercício aeróbico na fase de recuperação da lesão renal aguda induzida por gentamicina em ratos(Universidade Federal de São Paulo (UNIFESP), 2015-02-28) Oliveira, Clemerson dos Santos [UNIFESP]; Higa, Elisa Mieko Suemitsu [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introdução: A gentamicina (G) é um antibiótico muito utilizado para tratar infecções causadas por bactérias Gram-negativas, porém seu efeito colateral principal é a necrose tubular aguda e geração de espécies reativas de oxigênio (ROS). A atividade física regular é uma forma não farmacológica para prevenir muitas doenças, como a hipertensão e/ou diabetes. O objetivo deste estudo foi avaliar o efeito do exercício aeróbico na fase de recuperação da lesão renal aguda (LRA) induzida pela G em ratos. Métodos: Ratos Wistar machos com 12 semanas de idade foram distribuídos em 4 grupos (n = 6): A10+R30 e G10+R30 receberam água (veículo) ou G (100 mg/kg/dia, ip), respectivamente, durante 10 dias e ambos os grupos permaneceram 30 dias em repouso; A10+EX30 e G10+EX30 receberam água ou G, respectivamente, durante 10 dias e ambos treinaram por 30 dias. O treinamento físico foi realizado em esteira, a 16m/min, 60 min/dia, 5 dias/semana durante 4 semanas. Os ratos foram colocados em gaiolas metabólicas para avaliação individual dos dados metabólicos (diurese, ingestão alimentar e hídrica e massa corporal), análise da função renal (creatinina, ureia, proteinúria), óxido nítrico (NO) e TBARS, em 2 períodos: depois de 10 dias com água ou G e após 30 dias de repouso ou exercício. Os rins foram coletados para dosagem de NO, TBARS, superóxido dismutase (SOD), catalase (CAT), glutationa total (GSH) e análise histológica. Resultados: No 10º dia de G, a função renal estava prejudicada, mas foi restaurada após 30 dias de descanso ou exercício sem diferença estatística entre esses grupos. Nos grupos G10+EX30 vs. G10+R30, a síntese de NO estava aumentada no plasma e urina e reduzida no tecido renal; os níveis de TBARS estavam reduzidos no plasma, urina e tecido renal, enquanto que os antioxidantes CAT e GSH estavam aumentados (p<0,05); entre esses dois grupos não houve diferença estatística na análise histológica. Conclusão: O exercício aeróbico restaurou o NO, reduziu as ROS e aumentou a defesa antioxidante, sem prejudicar a recuperação da LRA induzida por G nos animais, sugerindo que o treinamento poderia ser utilizado como uma ferramenta coadjuvante, benéfica no tratamento da nefrotoxicidade, protegendo o rim frente a novas lesões.
- ItemAcesso aberto (Open Access)Endothelial, renal and hepatic variables in wistar rats treated with Vancomycin(Academia Brasileira de Ciências, 2014-12-01) Bruniera, Felipe R.; Ferreira, Felipe M.; Savioli, Luiz R.m.; Bacci, Marcelo R.; Feder, David; Pereira, Edimar Cristiano [UNIFESP]; Pedreira, Mavilde da Luz Gonçalves [UNIFESP]; Peterlini, Maria Angélica Sorgini [UNIFESP]; Perazzo, Fábio Ferreira [UNIFESP]; Azzalis, Ligia Ajaime [UNIFESP]; Rosa, Paulo César Pires [UNIFESP]; Junqueira, Virginia Berlanga Campos [UNIFESP]; Sato, Monica A.; Fonseca, Fernando Luiz Affonso [UNIFESP]; Faculdade de Medicina do ABC Departamento de Morfologia Disciplina de Farmacologia; Universidade Federal de São Paulo (UNIFESP)Vancomycin (VCM) is indicated in combat against Gram-positive infections, but it is not considered a first-choice drug because of its adverse effects. It is believed that oxidative stress is the primary mechanism of endothelial injury and the consequent VCM toxicity, which varies from phlebitis to nephrotoxicity. Moreover, dose recommendations, dilution, rates and types of infusion are still controversial. The aim of this study was to determine the effect of different VCM dilutions in endothelial, liver and kidney injuries by biochemical parameters and histopathological analysis. Wistar rats were randomly divided into six groups and subjected to femoral vein cannulation for drug administration. Control groups received 0.9 ml of saline and the others received VCM (10mg/Kg/day) at dilutions of 5.0 and 10.0 mg/mL for 3 and 7 days. Homocysteine, hs-CRP, AST, ALT, GGT, urea, creatinine, lycopene, alpha-tocopherol, beta-carotene and retinol were analyzed. Kidney, liver and cannulated femoral vein fragments were collected.This study showed alterations in ALT which featured hepatotoxicity. However, drug dilutions were not able to show changes in other biochemical parameters. In contrast, kidney and endothelium pathological changes were observed. More studies are needed to characterize VCM induced kidney and endothelium toxicity and biochemical markers able to show such morphological modifications.
- ItemSomente MetadadadosEstresse oxidativo como indutor da transição epitélio-mesemquimal em célula tubular renal(Universidade Federal de São Paulo (UNIFESP), 2013-06-26) Carrasco, Flavio Balbera [UNIFESP]; Silva Filho, Alvaro Pacheco e Silva Filho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)A nefropatia crônica do enxerto (NCE) é um grande obstáculo para o estabelecimento de longa sobrevida do transplante. A característica histológica que mais se associa ao declínio da função renal nesta patologia é a fibrose túbulo-intersticial (FTI) e atrofia tubular (AT). Estudos recentes sugerem que alguns miofibroblastos intersticiais derivam de células epiteliais tubulares renais que passaram pelo processo de transição epitelial-mesenquimal (TEM). Uma série de insultos incluindo o estresse oxidativo (OS), como o peróxido de hidrogênio (H2O2), e a exposição a citocinas pró-inflamatórias, como o fator de crescimento transformador beta 1 (TGF-β1), contribuem para a patogênese da fibrose em NCE. Além disso, o papel de substâncias antioxidantes na inibição da TEM tem sido alvo de diversos estudos. O presente estudo teve como objetivo a análise da ação do estresse oxidativo no processo de TEM in vitro e a supressão da transformação fibroblástica, ou seja, da TEM, frente a inibidores de EROs com a utilização de antioxidante. Para tal, células de linhagem humana oriundas do epitélio proximal tubular renal (HK-2) foram tratadas com H2O2 para indução da TEM e o TGF-1 foi utilizado como estímulo para controle positivo. As doses e tempos de tratamento foram estabelecidos por testes de viabilidade utilizando cristal violeta e a constatação da TEM foi dada por microscopia óptica, ensaios de motilidade celular, imunoblotting e imunocitoquímica com a marcação de moléculas relacionadas ao processo da TEM tais como citoqueratina, tipicamente expressa no citoesqueleto de células epiteliais, e vimentina, característica de células mesenquimais. O tratamento das células HK-2 com H2O2 e TGF-β1, resultou em alteração da morfologia celular à microscopia óptica, de um aspecto cubóide, tipicamente epitelial, a fusiforme, característico de células mesenquimais. Ensaios de viabilidade evidenciaram dose subletal de H2O2 de 0,10 mM/mL; contudo, quando submetidas ao teste de microscopia óptica e mobilidade celular, o tratamento com H2O2 nas doses de 0,25 e 0,50 mM/mL por 48 e 72 horas proporcionaram os melhores resultados, sem evidência de morte celular com tais doses. Tais resultados foram corroborados pela análise por imunocitoquímica, na qual as células submetidas ao estresse oxidativo por 48 e 72 horas com H2O2 e TGF-β1 tiveram uma diminuição significante da expressão de citoqueratina e aumento da expressão de vimentina, achados também confirmados através de immunoblotting, corroborando a capacidade de indução da TEM pelo OS. Em contrapartida avaliamos a capacidade de uma substância antioxidante, a N-acetilcisteína (NAC), em inibir o processo de TEM induzido pelo H2O2 utilizando imunocitoquímica, de modo que o pré-tratamento com NAC por 1 hora foi suficiente para a inibição da TEM observada através da persistência da expressão de citoqueratina e inibição da expressão da vimentina nas células epiteliais em estudo, quando expostas por 48 e 72 horas ao estímulo com TGF-b e H2O2. Em conclusão, as alterações morfológicas características da TEM puderam ser induzidas pelo estresse oxidativo com H2O2, em células epiteliais tubulares renais em cultura. Além disso, o processo de TEM neste modelo foi eficientemente inibido pelo tratamento com NAC, um antioxidante, sugerindo o papel fundamental do estresse oxidativo na TEM e a possibilidade terapêutica para prevenção dos eventos biológicos deletérios relacionados à TEM. Novos estudos em outros modelos são ainda necessários para a elucidação dos mecanismos envolvidos, bem como a efetividade e segurança para a aplicabilidade clínica de tais conceitos.
- ItemAcesso aberto (Open Access)Estresse oxidativo no plasma sanguíneo de indivíduos submetidos ao esforço físico agudo seguido de crioimersão corporal(Universidade de São Paulo, 2012-09-01) Prado, Fernanda Peres; Paludetto, Deise Regina Barbosa; Bachur, Cynthia Antonia Kallas; Freitas, Roseli Aparecida Leite de; Zaia, José Eduardo; Barros Neto, Turibio Leite de [UNIFESP]; Garcia, Sérgio Britto; Alves, Ana Carolina Araruna; Carvalho, Paulo Tarso Camilo de; Bachur, José Alexandre; UNIFRAN; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Universidade Nove de Julho (UNINOVE); UNINOVEThe purpose of this study was to analyze the influence of cold water immersion (CWI) following acute physical exercise on the oxidative stress in the blood plasma. Twelve men with average age of 22±1 years old, participated this study. All of them underwent the treadmill stress test followed by CWI in tank with water at 10ºC for 10 minutes. During this process, they were monitored and a set of parameters were analyzed: physical effort perception (Borg Scale), Heart Rate (HR), Blood Pressure (BP) and body heat, by measuring tympanic temperature. The morphological analysis of oxidative stress in blood plasma was done in accordance with a method known as Optical Morphology of the Oxidative Stress on Blood Plasma, which uses drops of capillary blood. A significant increase (p<0.01) in the rate of oxidative stress in plasma was noted after intense physical effort when compared with the rate of stress while at rest. However, the stress rate was significantly decreased (p<0.001) after CWI. Although further scientific studies should be carried out on the above mentioned test, may be concluded that, in the present study, the test has proven itself viable. The data found in the present study suggest that cold water immersion at 10ºC for 10 minutes following high intensity physical effort appears to be an important physical therapeutic measure towards the normalization of oxidative stress.
- ItemSomente MetadadadosEstudo da participação da proteína impact nos efeitos da restrição calórica em cElegans(Universidade Federal de São Paulo (UNIFESP), 2015-06-24) Conceicao, Rafael Ferraz [UNIFESP]; Mori, Marcelo Alves da Silva Mori [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)In recent decades, obesity has come to become a major global public health problem, resulting in the increased prevalence of chronic diseases such as coronary heart disease, type 2 diabetes, cancer, among others. Likewise, the increase in the elderly population has contributed to the increased incidence of these and other chronic diseases. Data in the literature suggest that caloric restriction may be an etfective intervention to combat the evils arising from obesity and aging, despi te the practical limitations underlying prolonged food restriction. Therefore, it is important that nutritional or pharmacological alternatives are developed to mimic the effects of caloric restriction without its deleterious etfects. Recent1y, it was demonstrated that the restriction of specific amíno acíds is sufficient to promote some acute effects of caloric restriction in mice, this being dependent on GCN2, a kinase activated by amino acid restriction that controls protein synthesis and stress responses. Our group and other groups also showed that the miRNA processing pathway is essential for the effects of caloric restriction to take place, whereas overexpression of Dicer, an enzyme important in the synthesis of miRNAs, leads to an increase in life expectancy and stress resistance in the nematode C. elegans. Thus, to better define the mechanisms of action of caloric restriction in relation to life expectancy and stress resistance, we will use C. elegans to test: 1) whether the GCN2 pathway controls lifespan, stress response and lipid accumulation of nematodes and 2) whether this pathway operates in the promotion of longevity and stress resistance induced by caloric restriction or Dicer overexpression. With this, we aim to contribute to the understanding ofthe mechanisms of action of caloric restriction, hoping to
- ItemSomente MetadadadosFibroblast growt factor 23 and dietary factors in renal disease(Universidade Federal de São Paulo (UNIFESP), 2016-10-25) Baia, Leandro da Cunha [UNIFESP]; Heilberg, Ita Pfeferman [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Klotho, um hormônio secretado pelo rim, atua como co-fator para a ativação do receptor do fator de crescimento fibroblástico 23 (FGF-23), o qual exerce importante função no metabolismo mineral pelo seu efeito fosfatúrico e inibitório da forma ativa da 1,25-dihidroxivitamina D3, [1,25(OH)2D3], e modulatório sobre o PTH. Estudos prévios têm demonstrado uma associação inversa entre níveis séricos de 25 hidroxivitamina D3, 25(OH)D3, e pressão arterial. Além disso, uma inversa relação entre inflamação e estresse oxidativo com a expressão de klotho tem sido reportada. As espécies reativas de oxigênio (EROs) são importantes mediadores da inflamação endotelial e podem contribuir para o desenvolvimento de aterosclerose através da estimulação de vias pró-inflamatórias no endotélio vascular. Os ácidos graxos poliinsaturados de cadeia longa (LCPUFAs), principalmente os da série ômega-3, como o ácido docosahexaenóico (DHA) e o ácido eicosapentaenóico (EPA), exercem um efeito protetor nas doenças cardiovasculares reduzindo a morbi-mortalidade devido aos seus potenciais efeitos anti-aterogênicos e anti-inflamatórios. Objetivos: Investigar os efeitos do DHA sobre a inflamação, estresse oxidativo, ativação do sistema renina-angiotensina-aldosterona e expressão de klotho em nível renal , em um modelo experimental de inflamação. Metodologia: Camundongos C57BL/6, com idade de 12 semanas, serão aclimatizados por 8 dias antes do início do estudo, mantidos em temperatura em torno de 22ºC e 50-60% de umidade relativa com ciclo claro/escuro de 12h. Durante o período de aclimatização, os animais serão alimentados com dieta padrão e terão livre acesso à água. Posteriormente, os animais serão divididos em 4 grupos e tratados durante 12 semanas: Grupos Controle (n=14): Os animais receberão dieta padrão e terão livre acesso à água por 10 dias. A partir do 11º dia os animais serão randomizados em 2 subgrupos: 1. (C-S): Controle + óleo de soja [dieta padrão + 7% de óleo de soja], (n=7) 2. (C-DHA): Controle + DHA [dieta padrão + 6.3% de óleo de peixe e 0.7% óleo de soja], (n=7). Grupos Adenina (n=14): Inflamação será induzida através da administração de adenina. Os animais serão alimentados com ração padrão enriquecida com 0,25% de adenina e terão livre acesso à água por 10 dias. A partir do 11º dia os animais serão randomizados em 2 subgrupos : 3. ADN-S [dieta padrão adicionada de adenina + 7% de óleo de soja], (n=7) 4. ADN-DHA [dieta padrão adicionada de adenina + 6.3% de óleo de peixe e 0.7% de óleo de soja], (n=7) As dietas serão obtidas da PragSoluções (Jaú, São Paulo, Brazil) e terão conteúdo energético similar. Uma amostra única de sangue será coletada do plexo ocular dos animais para a determinação de citocinas inflamatórias (TNF-?, IL-6, IL-1?), PTH, FGF23, creatinina e marcadores de estresse oxidativo (reduced/oxidized glutationa reduzida/oxidada ? razão GSH/GSSG). Angiotensina II, renina, catepsina B e pro-renina, também serão determinados. Ao final do estudo, os animais serão sacrificados com a utilização de anestésicos injetáveis (Cloridrato de Xilazina 10 mg/kg e Ketamina 50 mg/kg). Um rim será extraído, lavado com salina, pesado, congelado em nitrogênio liquido e armazenados à -80ºC para determinação da expressão de klotho através de RT-PCR.
- ItemSomente MetadadadosInfluência dos fatores femininos de infertilidade no estresse oxidativo do líquido folicular de pacientes submetidas a estímulo ovariano controlado(Universidade Federal de São Paulo (UNIFESP), 2014-04-15) Lima, Camila Bruna de [UNIFESP]; Lo Turco, Edson Guimaraes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Purpose: The present study aimed to evidence the oxidative status of follicular fluid from women submitted to in vitro fertilization treatments in order to establish a relationship between oxidative stress (OS) and the pathophysiology of different diseases like Polycystic Ovary Syndrome (PCOS) and Endometriosis. This study also aimed to correlate the OS with factors that may influence the success of assisted reproduction techniques such as the ovarian response to exogenous hormonal stimulation. Methods: This study included 183 patients referred to the Human Reproduction Service of Sao Paulo Hospital for in vitro fertilization treatments. They were separated according to the fertility factor to form the following groups: Controls (n=49), Endometriosis (n=48), Poor response (n=26), PCOS (n=15) e Hyper response (n=46). All patients were submitted to controlled ovarian hyper stimulation protocols and ovarian punction for follicular fluid collection. Results: The levels of oxidative stress were significantly higher in the groups Endometriosis (p=9,57x10-13), PCOS (p=0,00015) and Hyper response (p=7,04x10-7) when compared to Control group. In endometriosis group, it is possible to observe a positive correlation between FSH and LH serum levels (r=0,315 e p=0,031), and also between FSH and age (r=0,306 e p=0,035). It was not possible to find significant differences in OS levels on the comparison between Poor response and Control groups. (p=0,808). The moving average analysis showed a trend for increasing oxidative status with increasing age in patients who had hyper response to ovarian stimulation. It also showed a reduction in OS levels with increasing age in Endometriosis group. Pregnancy rates did not present statistically relevant differences among groups (p=0,381). Conclusions: In Endometriosis, PCOS and Hyper response groups, higher amounts of end products of lipid peroxidation were detected in follicular fluid. This highlights an elevated oxidative status in these patients. Moreover, the age seems to influence the levels of oxidative stress in Endometriosis and Hyper response groups. However, it was not possible to correlate oxidative stress with poor response or pregnancy rates.
- ItemAcesso aberto (Open Access)Mitochondrial DNA damage associated with lipid peroxidation of the mitochondrial membrane induced by Fe2+-citrate(Academia Brasileira de Ciências, 2006-09-01) Almeida, Andréa M.; Bertoncini, Clelia Rejane Antonio [UNIFESP]; Borecký, Jiri; Souza-Pinto, Nadja C.; Vercesi, Aníbal E.; Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Viçosa Departamento de Biologia Vegetal; National Institute on Aging Laboratory of Molecular GerontologyIron imbalance/accumulation has been implicated in oxidative injury associated with many degenerative diseases such as hereditary hemochromatosis, beta-thalassemia, and Friedreich's ataxia. Mitochondria are particularly sensitive to iron-induced oxidative stress - high loads of iron cause extensive lipid peroxidation and membrane permeabilization in isolated mitochondria. Here we detected and characterized mitochondrial DNA damage in isolated rat liver mitochondria exposed to a Fe2+-citrate complex, a small molecular weight complex. Intense DNA fragmentation was induced after the incubation of mitochondria with the iron complex. The detection of 3' phosphoglycolate ends at the mtDNA strand breaks by a 32P-postlabeling assay, suggested the involvement of hydroxyl radical in the DNA fragmentation induced by Fe2+-citrate. Increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine also suggested that Fe2+-citrate-induced oxidative stress causes mitochondrial DNA damage. In conclusion, our results show that iron-mediated lipid peroxidation was associated with intense mtDNA damage derived from the direct attack of reactive oxygen species.