Conselho Nacional de Desenvolvimento Científico e Tecnológico / O desenvolvimento de fibrose pulmonar (FP) induzida por bleomicina tem sido associado com as características genéticas e estresse oxidativo. Nosso objetivo foi investigar a influência do equilíbrio redox sobre a resistência a fibrose pulmonar induzida por bleomicina em diferentes linhagens de camundongos. Uma única dose de bleomicina (0,1 U/camundongo) ou salina (50 mL) foi administrada por via intratraqueal (i.t.) em camundongos C57BL/6, DBA/2 e camundongos BALB/c. Vinte e um dias após a administração de bleomicina, a taxa de mortalidade foi acima de 50% em camundongos C57BL/6 e 20% em DBA/2, enquanto não foi observada em BALB/c. Houve um aumento na elastância (p<0.001), &#916;P2 (p<0.05), &#916;Ptot (p<0.01) e DE,l (p<0.05) em camundongos C57BL/6. O volume dos septos aumentaram em camundongos C57BL/6 (p<0.05) e DBA/2 (p<0.001). Os níveis de INF-&#947; foram reduzidas em camundongos C57BL/6 (p<0.01). Níveis OH-prolina foram aumentados em camundongos C57BL/6 e DBA/2 (p<0.05). Atividade e expressão de SOD foram reduzidas em camundongos C57BL/6 e DBA/2 (p<0.001 e p<0.001, respectivamente), enquanto que a atividade de CAT reduziu em todas as linhagens (C57BL/6: p<0.05; DBA/2: p<0.01, BALB/c: p<0.01). A atividade da GPx e expressão GPx 1/2 diminuiram em camundongos C57BL/6 (p<0.001). Nós concluímos que a resistência da FP pode também estar relacionada com a atividade e expressão de SOD em camundongos BALB/c / The development of bleomycin-induced pulmonary fibrosis (PF) has been associated with differences in genetic background and oxidative stress status. Our aim was to investigate the cross-talk between the redox profile, lung architecture and function in PF in different mouse strains. A single dose of either bleomycin (0.1 U/mouse) or saline (50 &#956;L) was by intratracheal (i.t.) administration in C57BL/6, DBA/2 and BALB/c mice. Twenty-one days after bleomycin, the mortality rate was over 50% in C57BL/6 and 20% in DBA/2 mice and PF was not observed in BALB/c. There was an increase in Est (p<0.001), &#916;P2 (p<0.05), &#916;Ptot (p<0.01) and &#916;E (p<0.05) in C57BL/6 mice. Septa volume increase in C57BL/6 (p<0.05) and DBA/2 (p<0.001). The levels of INF-&#947; were reduced by in C57BL/6 mice (p <0.01). OH-proline levels were increased in C57BL/6 and DBA/2 mice (p<0.05). SOD activity and expression was reduced in C57BL/6 and DBA/2 mice (p<0.001 and p<0.001 respectively), whereas CAT was reduced in all strains 21 days following bleomycin when compared to saline groups (C57BL/6: p<0.05; DBA/2: p<0.01, BALB/c: p<0.01). GPx activity and GPx1/2 expression decreased in C57BL/6 (p<0.001). We conclude that the PF resistance may also be related to the activity and expression of SOD in BALB/c

Orientador: Roberto Carlos Burini / Resumo: A prevalência mundial de Síndrome Metabólica (SM) está aumentando drasticamente nos últimos anos. Esta desordem consiste de um conjunto de condições metabólicas, contemplando hiperadiposidade abdominal, resistência insulínica (RI), dislipidemia e hipertensão, e é fator de risco para o desenvolvimento de Diabetes Mellitus tipo 2 (DM2) e doenças cardiovasculares (DCVs). Muitos estudos indicam a participação do estresse oxidativo (EO) junto com o estado estresse inflamatório (EI) como parte do desenvolvimento e agravamento da SM e surgimento das doenças crônicas não-transmissíveis (DCNTs). O EO é caracterizado como estado de desequilíbrio entre os sistemas oxidativo e antioxidante, resultando no excesso de espécies reativas de oxigênio (EROs), menor capacidade antioxidante e efeitos deletérios a tecidos e células. A regulação das reações de oxidação e redução são importantes para o controle de funções fisiológicas e combate ao estresse. Diante disso, os aminotióis ou compostos tio-redox (homocisteína, cisteína e glutationa) exercem importante papel no equilíbrio do estado redox celular. Neste artigo de revisão, analisamos os aspectos fisiopatológicos de compostos tio-redox no curso da SM. / Abstract: The worldwide prevalence of Metabolic Syndrome (MetS) has been increasing dramatically in recent years. MetS is a set of metabolic conditions, including abdominal hyperadiposity, insulin resistance, dyslipidemia and hypertension, and is a risk factor for the development of type 2 diabetes mellitus and cardiovascular diseases. Many studies indicate the participation of oxidative stress along with the pro-inflammatory state as part of the development and aggravation of MetS and emergence of chronic noncommunicable diseases. Oxidative stress is characterized as a state of imbalance between oxidative and antioxidant systems, resulting in excess of reactive oxygen species, lower antioxidant capacity and deleterious effects on tissues and cells. The regulation of the oxidation and reduction reactions are important for the control of physiological functions and the fight against stress. In view of this, the aminothiols or thiol-redox compounds (homocysteine, cysteine and glutathione) play an important role in the equilibrium of the cellular redox state. In this review article, we analyze the pathophysiological aspects of thiol-redox compounds in the course of MetS. / Mestre

Na Ficha Catalogr?fica consta o t?tulo: "Efeito da terapia por fotobiomodula??o (LED630nm) no equil?brio redox e nos aspectos hist?logicos da osteoartrite de joelho induzida por monoiodoacetato de s?dio em ratos". / Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2018-08-30T15:08:00Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) lorena_pacheco_oliveira_martins.pdf: 1327754 bytes, checksum: e69932636c7878e52b2b3d058f72ea94 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2018-10-01T17:08:53Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) lorena_pacheco_oliveira_martins.pdf: 1327754 bytes, checksum: e69932636c7878e52b2b3d058f72ea94 (MD5) / Made available in DSpace on 2018-10-01T17:08:53Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) lorena_pacheco_oliveira_martins.pdf: 1327754 bytes, checksum: e69932636c7878e52b2b3d058f72ea94 (MD5) Previous issue date: 2018 / A osteoartrite (OA) tem potencial cr?nico-degenerativo e car?ter inflamat?rio. Al?m do papel inflamat?rio, outros fatores, como o desequil?brio redox, parecem contribuir para altera??es na cartilagem articular, a principal estrutura articular afetada. A fotobiomodula??o (FBM) utilizando LED tem sido proposta para o tratamento da OA por atuar sobre os processos degenerativos da cartilagem, favorecer defesas antioxidantes e modular marcadores do estresse oxidativo. Diante disso, o objetivo foi avaliar o efeito da terapia por FBM utilizando LED (630 nm) sobre os aspectos histomorfom?tricos da cartilagem articular e no equil?brio redox na OA de joelho induzida por monoiodoacetato de s?dio em ratos. Foram utilizados 27 ratos Wistar, separados entre os grupos: Controle; osteoartrite (OA) e osteoartrite + LED (OALED). No grupo OALED foi aplicado o LED (630 nm; 300mW; 9 J/cm2; 0,3 W/cm2; 30 s; iniciando 24h ap?s indu??o; 3 vezes/semana; 8 semanas). A eutan?sia dos animais ocorreu 56 dias ap?s a indu??o da OA, o sangue foi coletado para an?lise do dano oxidativo (TBARS), da capacidade antioxidante enzim?tica (atividade da SOD e CAT) e o estado antioxidante total do plasma atrav?s (FRAP). O joelho direito foi utilizado para a morfometria da cartilagem atrav?s da medida da espessura e contagem de condr?citos. O grupo OALED apresentou maior espessura m?dia da cartilagem e m?dia dos condr?citos semelhante ao grupo Controle. Foi observado ainda maior atividade enzim?tica antioxidante (SOD e CAT) e menor concentra??o de TBARS (P<0,05) no grupo OALED comparado ao grupo OA. A terapia por FBM demonstrou ser efetiva sobre o equilibro redox e sobre a preserva??o da cartilagem articular em um modelo de OA induzida. / Disserta??o (Mestrado) ? Programa de P?s-Gradua??o em Reabilita??o e Desempenho Funcional, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2018. / Osteoarthritis (OA) has chronic-degenerative potential and inflammatory character. In addition to the inflammatory role, other factors, such as redox imbalance, appear to contribute to changes in the articular cartilage, the main articular structure affected. Photobiomodulation (PBM) using LED has been proposed for the treatment of OA by acting on degenerative cartilage processes, favoring antioxidant defenses and modulating oxidative stress markers. The aim of this study was to evaluate the effect of PBM therapy using LED (630 nm) on the histomorphometric aspects of articular cartilage and redox balance in knee OA induced by sodium monoiodoacetate in rats. Wistar rats were used, separated between the groups: Control; osteoarthritis (OA) and osteoarthritis + LED (OALED). In the OALED group, the LED (630 nm, 300 mW, 9 J / cm2, 0.3 W / cm2, 30 s, starting 24 h after induction, 3 times / week, 8 weeks) was applied. The euthanasia of the animals occurred 56 days after induction of OA, blood was collected for analysis of oxidative damage (TBARS), enzymatic antioxidant capacity (SOD and CAT activity) and the total antioxidant status of plasma through (FRAP). The right knee was used for the morphometry of cartilage by measuring the thickness and counting of chondrocytes. The OALED group had a higher average cartilage thickness and mean chondrocytes similar to the control group. It was also observed higher antioxidant enzymatic activity (SOD and CAT) and lower level of TBARS (P <0.05) in the OALED group compared to the OA group. PBM therapy has been shown to be effective on redox balance and preservation of articular cartilage in an induced OA model.

Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2018-09-27T19:30:21Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) amanda_escobar_teixeira.pdf: 1867154 bytes, checksum: a9782b1752452b0bdb34a3ba10ae56bb (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2018-10-01T17:48:46Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) amanda_escobar_teixeira.pdf: 1867154 bytes, checksum: a9782b1752452b0bdb34a3ba10ae56bb (MD5) / Made available in DSpace on 2018-10-01T17:48:46Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) amanda_escobar_teixeira.pdf: 1867154 bytes, checksum: a9782b1752452b0bdb34a3ba10ae56bb (MD5) Previous issue date: 2018 / Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O objetivo deste trabalho foi avaliar os efeitos da dieta de cafeteria desde a lacta??o nos par?metros nutricionais e na a??o da risperidona nos comportamentos de ansiedade, locomo??o, mem?ria e intera??o social. Foram utilizadas 14 ninhadas de ratos da linhagem Wistar (Rattus novergicus) alojados em gaiolas individuais, sob condi??es padr?o. Os ratos machos de cada ninhada formaram, da lacta??o at? a fase adulta, os grupos: Controle (CTRL) ? receberam ra??o padr?o e ?gua ad libitum (n = 42); Cafeteria (CAF) ? receberam dieta de cafeteria e ?gua ad libitum (n = 42). Entre o 114? e o 119? dia de vida, os animais foram subdividos (n = 21) para receberem o tratamento com salina (CTRL-S e CAF-S) ou risperidona (CTRL-R e CAF-R). Nesse per?odo foram realizados os testes comportamentais do labirinto em cruz elevado, campo aberto, teste de reconhecimento de objetos e intera??o social. No 119? os animais foram colocados em jejum, para que, no 120? dia fossem anestesiados e eutanasiados por exsanguina??o. Foram avaliados: consumo de ra??o, ingest?o cal?rica, peso corporal, ganho de peso, coeficiente de efici?ncia alimentar (CEA), comprimento naso-anal e ?ndice de massa corporal (IMC); peso dos ?rg?os e do tecido adiposo abdominal; teores de colesterol total e fra??es, triacilglicerol e glicemia do soro; teor de lip?dios, colesterol total e triacilglicerol do f?gado e das fezes; estado redox do f?gado e de diferentes por??es do enc?falo (c?rtex pr?-frontal e hipocampo). Foi utilizada an?lide de vari?ncia (ANOVA) seguida de Newman Keuls quando necess?rio (P<0,05). O grupo CAF demonstrou menor ingest?o alimentar e maior ingest?o cal?rica, devido ? densidade energ?tica da dieta. O maior consumo cal?rico se configurou em maior ganho de peso, CEA, IMC e ac?mulo de tecido adiposo abdominal. O grupo CAF tamb?m obteve eleva??o dos n?veis de triacilglicerol plasm?ticoa, al?m de lip?dios e triacilglicerol hep?tico, que foram classificados em esteatose hep?tica. Ao mesmo tempo, houve uma rela??o ruim entre as fra??es do colesterol plasm?tico (HDL-c, LDL-c e VLDL-c), com aumento do risco de doen?as aterog?nicas. Portanto, a dieta de cafeteria foi capaz de reproduzir um modelo de obesidade humana e de s?ndrome metab?lica. Os animais do grupo de cafeteria apresentaram caracter?sticas de estresse oxidativo no hipocampo, o que pode comprometer a fun??o dessa estrutura e promover altera??es comportamentais. O grupo CAF - S obteve efeito ansiol?tico devido ao maior n?mero de entradas e tempo gasto no centro do campo aberto, al?m de maior locomo??o atrav?s do maior n?mero de quadrantes percorridos. CAF - S ainda demonstrou preju?zos na mem?ria avaliados atrav?s do teste de reconhecimento de objetos e diminui??o da intera??o social. Tais efeitos podem estar associados a altera??es no sistema serotonin?rgico desses animais. CAF - R demonstrou efeito ansiog?nico e diminui??o na locomo??o no campo aberto. No teste de reconhecimento de objetos, houve diminui??o na intera??o com os objetos, sem, no entanto, melhorar o ?ndice de discrimina??o em rela??o a CAF - S. No teste de intera??o social, CAF - R obteve maior sociabilidade. Os resultados da administra??o da risperidona indicam que esta droga possui um efeito diferente quando aplicada em animais que foram tratados com dieta de cafeteria desde a lacta??o. / Disserta??o (Mestrado) ? Programa de P?s-gradua??o em Ci?ncias Farmac?uticas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2018. / The objective of this work was to evaluate the effects of the cafeteria diet from lactation on the nutritional parameters and the action of risperidone on the behaviors of anxiety, locomotion, memory and social interaction. Fourteen litters of Wistar rats (Rattus novergicus) housed in individual cages were used under standard conditions. The male rats from each litter formed from the lactation to the adult phase, the groups: Control (CTRL) - received standard chow and water ad libitum (n = 42); Cafeteria (CAF) - received cafeteria diet and water ad libitum (n = 42). Between days 114 and 119, animals were subdivided (n = 21) to receive treatment with saline (CTRL-S, CAF-S) or risperidone (CTRL-R and CAF-R). During this period, the behavioral tests of the plus maze size, open field, test of object recognition and social interaction were performed. At 119? the animals were fasted, so that on the 120? day they were anesthetized and euthanized by exsanguination. The following were evaluated: feed intake, caloric intake, body weight, weight gain, food efficiency coefficient (FEC), naso-anal length and body mass index (BMI); weight of organs and abdominal adipose tissue; levels of total cholesterol and fractions, triacylglycerol and serum glycemia; lipid content, total cholesterol, and triacylglycerol of liver and faeces; redox status of the liver and different portions of the encephalon (prefrontal cortex and hippocampus). Variance analysis (ANOVA) was used followed by Newman Keuls when necessary (p<0,05). The CAF group demonstrated lower dietary intake and higher caloric intake, due to the energy density of the diet. The highest caloric intake was in greater weight gain, FEC, BMI and abdominal adipose tissue accumulation. The CAF group also achieved elevations in plasma triglyceride levels, besides lipids and hepatic triacylglycerol, which were classified as hepatic steatosis. At the same time, there was a poor relationship between fractions of plasma cholesterol (HDL-c, LDL-c and VLDL-c), with increased risk of atherogenic diseases. Therefore, the cafeteria diet was able to reproduce a model of human obesity and metabolic syndrome. The animals in the cafeteria group presented oxidative stress characteristics in the hippocampus, which may compromise the function of this structure and promote behavioral changes. The CAF - S group had an anxiolytic effect due to the greater number of entrances and time spent in the center of the open field, besides greater locomotion through the greater number of quadrants traveled. CAF - S also demonstrated memory impairments assessed through the object recognition test and decreased social interaction. Such effects may be associated with changes in the serotonergic system of these animals. CAF - R demonstrated an anxiogenic effect and decreased locomotion in the open field. In the object recognition test, there was a decrease in the interaction with the objects, without, however, improving the discrimination index in relation to CAF - S. In the social interaction test, CAF - R obtained greater sociability. The results of the administration of risperidone indicate that this drug has a different effect when applied in animals that have been treated with cafeteria diet since lactation.

Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2018-08-09T22:31:02Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) daniel_almeida_freitas.pdf: 2420619 bytes, checksum: eef5412551343ea7660ddfdaac19b6e2 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2018-10-05T19:33:26Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) daniel_almeida_freitas.pdf: 2420619 bytes, checksum: eef5412551343ea7660ddfdaac19b6e2 (MD5) / Made available in DSpace on 2018-10-05T19:33:26Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) daniel_almeida_freitas.pdf: 2420619 bytes, checksum: eef5412551343ea7660ddfdaac19b6e2 (MD5) Previous issue date: 2017 / Funda??o de Amparo ? Pesquisa do estado de Minas Gerais (FAPEMIG) / O treinamento f?sico de intensidade leve e moderada est?o associados a efeitos neurais ben?ficos, contudo o exerc?cio de alta intensidade cont?nuo a efeitos neurais mal?ficos, pouco ? conhecido sobre os efeitos do treinamento intervalado de alta intensidade em ingl?s high intensity interval training (HIIT) em par?metros neuroqu?micos e de mem?ria. O presente estudo avaliou em ratos da linhagem Wistar os efeitos de 6 semanas de HIIT sobre o estado redox, concentra??o de mediadores inflamat?rios fator de necrose tumoral alfa (TNF-?), interleucina 1-beta (IL-1?), interleucina 6 (IL-6) e interleucina 10 (IL-10) e do fator neurotr?fico derivado c?rebro, do ingl?s brain derived neurothrophic factor (BDNF) no hipocampo e c?rtex cerebral. Al?m disso, foi avaliado o desempenho nas tarefas de reconhecimento espacial de objeto (hipocampo-dependente) e tarefa de reconhecimento de novo objeto (c?rtex-dependente). O presente estudo aprovado pela Comiss?o de Experimenta??o Animal (CEUA-UFVJM) sob n?mero de protocolo (031/2015). Ap?s 6 semanas de HIIT, os animais apresentaram redu??o de 28,57% do conte?do de esp?cies reativas ao ?cido tiobarbit?rico (TBARS) e aumento de 75% da atividade da enzima super?xido dismutase (SOD) e de 50,83% da capacidade antioxidante total pelo m?todo de redu??o do ferro (FRAP - ?Ferric reducing ability of plasma).no hipocampo. Al?m disso, o HIIT reduziu a concentra??o de mediadores neuroimunes no hipocampo (TNF-?, IL-1?, IL-6 e IL-10) respectivamente em (24,8%;13,9%; 33,93% e 16,33%), aumentou a concentra??o de BDNF em 60,21% e n?o interferiu no desempenho dos animais nas tarefas de reconhecimento espacial de objeto e reconhecimento de novo objeto. Nenhum dos par?metros investigados foram alterados no c?rtex cerebral. O presente estudo mostrou efeito positivo de 6 semanas de HIIT espec?fico por regi?o cerebral, sendo que tais modifica??es resultaram em efeitos neurais ben?ficos no hipocampo de animais submetidos a um treinamento for?ado. / Disserta??o (Mestrado) ? Programa Multic?ntrico de P?s-gradua??o em Ci?ncias Fisiol?gicas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / Although High Intensity Interval Training (HIIT) is associated with neuroprotection, there is no information available on the balance of pro and anti-inflammatory cytokines, as well as redox status, expression of neurotrophins and their impacts on different neural substrates and cognitive function. The present study evaluated the effects of a 6 weeks HIIT protocol on redox homeostasis, concentration of tumor necrosis factor alpha (TNF-?), interleukin 1-beta (IL-1?), interleukin 6 (IL -6) and interleukin 10 (IL-10) and brain derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex of Wistar rats.In addition, we evaluated the performance in the object spatial recognition tasks (hippocampus-dependent) and the new object recognition task (cortex-dependent). After 6 weeks of the HIIT protocol, the animals showed a reduction in the content of thiobarbituric acid reactive species (TBARS) and an increase in the activity of the enzyme superoxide dismutase (SOD) and in the total antioxidant capacity evaluated by the iron reduction method (FRAP - Ferric reducing ability of plasma) in the hippocampus. In addition, HIIT reduced the concentration of neuroimmune mediators in the hippocampus (TNF-?, IL-1?, IL-6 and IL-10), increased BDNF concentration and did not interfere in the performance of animals in the object recognition task. None of the investigated parameters were altered in the cerebral cortex. The present study was the first to show positive effect of 6 weeks of HIIT on specific brain-region, and such modifications result in a neuroprotective effect in the hippocampus of animals submitted to the stress of forced training.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / As formas epimastigotas de Trypanosoma cruzi proliferam e se diferenciam no interior de diferentes compartimentos do trato digestivo dos triatomíneos. Esses ambientes antagônicos, no que diz respeito à concentração de nutrientes, pH e status redox, constituem um desafio para o protozoário por conterem moléculas e fatores capazes de deflagrar diferentes sinalizações e respostas no parasito. Por isso, testamos a influência de produtos abundantes do metabolismo do vetor e de status redox distintos, frente aos processos de proliferação e diferenciação in vivo e in vitro. Como exemplo temos o heme e a hemozoína, subprodutos da digestão da hemoglobina, e o urato, rico na urina dos insetos. O heme é uma importante molécula em todos os seres vivos. Nosso grupo mostrou seu papel na proliferação in vitro de T. cruzi e que esse sinal é governado pela enzima redox-sensível CaMKII (Lara et al., 2007; Souza et al., 2009). Esse efeito parece depender de uma sinalização redox, onde o heme e não seus análigos induz a formação de EROs, modulando a atividade da CaMKII (Nogueira et al, 2011). Apesar de gerar espécies reativas de oxigênio (EROs) em formas epimastigotas, o heme não alterou a ultraestrutura desses parasitos mostrando uma adaptação a ambientes oxidantes. Além disso, a adição de FCCP inibiu a formação de EROs mitocondrial, diminuindo a proliferação dos parasitos. Em contrapartida, a AA aumentou drasticamente a produção de EROs mitocondrial levando à morte dos epimastigotas. Estes resultados confirmam a hipótese de regulação redox do crescimento de epimastigotas. A formação de &#946;- hematina (hemozoína) constitui uma elegante estratégia para minimizar o efeito tóxico do heme nos insetos hematófagos. Contudo, a &#946;-hematina não influenciou a proliferação ou a metaciclogênese in vitro. Já o urato, e outros antioxidantes clássicos como o GSH e o NAC prejudicaram a proliferação in vitro de epimastigotas. Estes efeitos foram parcialmente revertidos quando os antioxidantes foram incubados juntamente com o heme. Durante a metaciclogênese in vitro, o NAC e o urato induziram um aumento significativo das formas tripomastigotas e levaram a diminuição da porcentagem de formas epimastigotas. Em contrapartida, o heme e a &#946;-hematina apresentaram o efeito oposto, diminuindo a porcentagem de formas tripomastigotas e aumentando a de epimastigotas. No intuito de confirmar a influencia do status redox na biologia do parasito in vivo, nós quantificamos a carga parasitária nas porções anterior e posterior e no reto do triatomíneo alimentado na presença ou na ausência de NAC e urato por qPCR. O tratamento com os antioxidantes aumentou a carga parasitária em todas as partes do intestino analisadas. Posteriormente, para diferenciar as formas evolutivas responsáveis pelo incremento da carga parasitária, foram realizadas contagens diferenciais nas mesmas porções do intestino do inseto vetor. Cinco dias após a infecção foi observado aumento significativo de formas tripomastigotas e diminuição de formas epimastigotas in vivo. Em conjunto, estes dados sugerem que, assim como a concentração de nutrientes e o pH, o status redox também pode influenciar a biologia do T. cruzi no interior do inseto vetor. Neste cenário, moléculas oxidantes agiriam a favor da proliferação, e em contraste, antioxidantes parecem favorecer a metaciclogênese. / Trypanosoma cruzi epimastigotes proliferate and differentiate inside different compartments of the triatomines gut. These environments are antagonic in terms of nutrient content, pH and redox status. All these factors represent a challenge to the protozoan due to the presence of molecules and factors which are able to induce different signals to the parasite. Thus, we tested the influence of abundant metabolism products of the vector, with distinct redox status, in the proliferation and metacyclogenesis in vitro and in vivo. These molecules are heme and hemozoin, both byproducts of hemoglobin digestion, and urate, present in the urine of insects. Heme is a ubiquitous molecule present in all living organisms. Our group studied its role in T. cruzi growth in vitro, showing that this signal is governed by the redox-sensitive enzyme CaMKII (Lara et al., 2007; Souza et al., 2009). Indeed, it seems to rely on a redox signaling pathway in which heme, but not its analogs, induces ROS formation, thus modulating CaMKII activity (Nogueira et al., 2011). Although it induces ROS in epimastigotes, the heme molecule had no deleterious effect upon the parasites ultrastructure, suggesting an adaptation to oxidative environments. In addition, FCCP inhibited mitochondrial ROS formation, then decreasing the parasite proliferation. On the other hand, AA drastically increased mitochondrial ROS production leading to cell death. These results corroborate the hypothesis of redox regulation of epimastigotes proliferation. Hemozoin (&#946;- hematin) formation is an elegant strategy to minimize the toxic effect of heme in hematophagous insects. However, &#946;-hematin had no influence upon the proliferation or metacyclogenesis in vitro. Also, urate, GSH and NAC impaired epimastigote proliferation. These effects were partially reversed when the antioxidants were incubated along with heme. During metacyclogenesis in vitro, NAC and urate induced a significant increment of trypomastigotes and decreased the percentage of epimastigotes. Heme and &#946;-hematin presented the opposite effect diminishing the percentage of trypomastigotes and increasing the percentage of epimastigotes. To confirm the influence of the redox status in the parasite biology in vivo, we quantified the parasite loads in the anterior and posterior midguts and in the rectum of the triatomine vector fed with or without NAC and urate by qPCR. The treatment with the antioxidants increased the parasite loads in all midgut sections analyzed. Afterwards, in order to distinguish the evolutive forms responsible for the increment of parasite loads, we performed differential counting of the midgut sections. Five days post infection we observed an increment of trypomastigotes and a decrease of epimastigote forms in vivo. Taken together, these data suggests that, as well as nutrient content and pH, the redox status may also influence T. cruzi biology in the vector. In this scenario, oxidants act to turn on proliferation and in contrast, antioxidants seem to switch the cycle towards metacyclogenesis.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / O desenvolvimento de fibrose pulmonar (FP) induzida por bleomicina tem sido associado com as características genéticas e estresse oxidativo. Nosso objetivo foi investigar a influência do equilíbrio redox sobre a resistência a fibrose pulmonar induzida por bleomicina em diferentes linhagens de camundongos. Uma única dose de bleomicina (0,1 U/camundongo) ou salina (50 mL) foi administrada por via intratraqueal (i.t.) em camundongos C57BL/6, DBA/2 e camundongos BALB/c. Vinte e um dias após a administração de bleomicina, a taxa de mortalidade foi acima de 50% em camundongos C57BL/6 e 20% em DBA/2, enquanto não foi observada em BALB/c. Houve um aumento na elastância (p<0.001), &#916;P2 (p<0.05), &#916;Ptot (p<0.01) e DE,l (p<0.05) em camundongos C57BL/6. O volume dos septos aumentaram em camundongos C57BL/6 (p<0.05) e DBA/2 (p<0.001). Os níveis de INF-&#947; foram reduzidas em camundongos C57BL/6 (p<0.01). Níveis OH-prolina foram aumentados em camundongos C57BL/6 e DBA/2 (p<0.05). Atividade e expressão de SOD foram reduzidas em camundongos C57BL/6 e DBA/2 (p<0.001 e p<0.001, respectivamente), enquanto que a atividade de CAT reduziu em todas as linhagens (C57BL/6: p<0.05; DBA/2: p<0.01, BALB/c: p<0.01). A atividade da GPx e expressão GPx 1/2 diminuiram em camundongos C57BL/6 (p<0.001). Nós concluímos que a resistência da FP pode também estar relacionada com a atividade e expressão de SOD em camundongos BALB/c / The development of bleomycin-induced pulmonary fibrosis (PF) has been associated with differences in genetic background and oxidative stress status. Our aim was to investigate the cross-talk between the redox profile, lung architecture and function in PF in different mouse strains. A single dose of either bleomycin (0.1 U/mouse) or saline (50 &#956;L) was by intratracheal (i.t.) administration in C57BL/6, DBA/2 and BALB/c mice. Twenty-one days after bleomycin, the mortality rate was over 50% in C57BL/6 and 20% in DBA/2 mice and PF was not observed in BALB/c. There was an increase in Est (p<0.001), &#916;P2 (p<0.05), &#916;Ptot (p<0.01) and &#916;E (p<0.05) in C57BL/6 mice. Septa volume increase in C57BL/6 (p<0.05) and DBA/2 (p<0.001). The levels of INF-&#947; were reduced by in C57BL/6 mice (p <0.01). OH-proline levels were increased in C57BL/6 and DBA/2 mice (p<0.05). SOD activity and expression was reduced in C57BL/6 and DBA/2 mice (p<0.001 and p<0.001 respectively), whereas CAT was reduced in all strains 21 days following bleomycin when compared to saline groups (C57BL/6: p<0.05; DBA/2: p<0.01, BALB/c: p<0.01). GPx activity and GPx1/2 expression decreased in C57BL/6 (p<0.001). We conclude that the PF resistance may also be related to the activity and expression of SOD in BALB/c

Pour mieux comprendre les éléments du métabolisme impliqués dans la détectionélectrochimique de bactéries et dans les biopiles bactériennes, le comportementélectrochimique de différentes souches de bactéries de type E. coli a été analysé. Lesbactéries ont été incubées dans un milieu de culture en présence de différents substrats,dans une cellule électrochimique à 3 électrodes où l’électrode de travail (ITO) agit en tantqu’accepteur d’électrons. En utilisant la voltampérométrie cyclique et lachronoampérométrie, l’accès aux caractéristiques électrochimiques des médiateurs redoxissus du métabolisme bactérien a ainsi pu être réalisé. Dans le cas des bactéries de typeE.coli XL1-Blue incubées en présence de sources différentes de carbone, telles que leglucose, le succinate ou l’acétate, il a été montré que les bactéries produisent un médiateurredox naturel, quelle que soit la source de carbone. Un courant électrique plus importantest obtenu dans le cas où un médiateur redox (PQQ or riboflavine) est ajouté dans lemilieu. Dans le cas des bactéries de type E.coli K12 et de ses souches mutantes ΔmenC etΔubiC incubées en présence de glucose ou de succinate, il a été trouvé que la soucheΔubiC produit un courant électrique plus élevé que E.coli K12 et ΔmenC. Il sembleraitainsi que la souche ΔubiC présente une activité électrochimique faisant intervenir un gènede régulation de la voie de synthèse de la ménaquinone. / To further understand the metabolism parameters involved in the electrochemicaldetection of bacteria and microbial fuel cell applications, the electrochemical behavior ofdifferent E. coli strains was analyzed. The bacteria were incubated in anaerobic conditionin a culture medium containing different substrates in a three-electrode electrochemicalcell where ITO working electrode serves as an electron acceptor. Using cyclic voltammetryand chronoamperometry, the electrochemical characteristics of excreted redox compoundsissued from bacterial metabolism have been assessed. In the case of E. coli XL1-Blue inpresence of different carbon sources such as glucose, succinate or acetate, the resultsshowed that a natural redox compound is produced whatever the carbon source. A higherelectrical current is obtained in the case of the addition of artificial mediators (PQQ orriboflavine) in the medium. In the case of E. coli K12 and its mutants ΔmenC and ΔubiCincubated in medium containing glucose or succinate, it is found that ΔubiC produced ahigher current compared to E.coli K12 and its mutants ΔmenC. It has been proposed thatΔubiC exhibits its electrochemical activity through the gene regulation of menaquinonesynthesis pathway.

Le fer joue un rôle majeur dans un grand nombre de processus biogéochimiques impliquant des transferts d'électrons, c'est-à-dire des réactions redox. Les argiles forment une famille de minéraux ubiquitaires, dont certains membres contiennent du fer au sein de leur structure. La structure des argiles confère à ce fer structural (Festr) des propriétés redox spécifiques. Celles-ci font l'objet d'un nombre croissant d'études, portant sur divers domaines de recherche, allant des études agronomiques sur l'accessibilité des nutriments dans les sols ou sur la maturation de la matière organique, aux études sur la rétention des métaux lourds ou des radioéléments dans des barrières argileuses. L'étude des propriétés redox du Festr demeure toutefois un challenge scientifique. La structure cristallographique des argiles conditionne les propriétés redox du Festr, mais les transformations redox du Festr ont également en retour un impact sur cette structure. Les propriétés structurales de l'argile et la manière dont elles évoluent au cours des processus redox sont ainsi influencées par l'histoire redox de l'argile, c'est-à-dire l'étendue et le nombre de cycles redox qu'elle a pu subir. Etant donnés le nombre et la complexité des mécanismes mis en jeu, et étant donné la variété des structures argileuses, les travaux de cette thèse se sont focalisés sur le groupe particulier des smectites dioctaédriques, plus précisément sur les membres ferrugineux que sont les nontronites, et sur l'impact de la réduction de leur Festr sur leurs propriétés structurales. Le mécanisme de réduction étudié est lui-même restreint à la réduction par de puissants agents réducteurs chimiques de type dithionite. En parallèle à un travail de revue critique de l'abondante littérature disponible sur cet aspect spécifique, des travaux expérimentaux ont été conduits et plusieurs approches théoriques ont été discutées et développées pour conduire à un modèle structural des propriétés redox du Festr et de leur relations avec la structure smectitique. De nouvelles mesures de charge négatives du feuillet argileux en fonction du niveau de réduction, réalisées au cours de cette thèse, indiquent clairement que, contrairement au comportement précédemment supposé, la charge structurale du feuillet n'augmente pas de façon monotone avec la réduction du Festr , mais est marquée par une chute significative à partir d'un niveau de réduction donné. Le domaine de réduction d'une nontronite est ainsi divisé en deux domaines : le premier est marqué par une augmentation de la charge négative et des changements structuraux réversibles ; le second est caractérisé par une chute de la charge négative et des transformations structurales moins ou non réversibles. Les efforts de modélisation réalisés durant cette thèse se sont restreints à la première phase de réduction, c'est-à-dire la phase réversible. Un premier modèle empirique permet de modéliser l'évolution de la CEC de nontronites à partir de leur formule structurale (qui donne la composition et la charge) et d'un paramètre empirique qui est commun à une série de nontronites pour lesquelles des données sont disponibles. Dans un second temps, un algorithme mimant la progression de la réduction du fer structural a été mis au point, permettant de lier l'évolution de la charge négative d'un type particulier de nontronites (pauvre en fer tétraédrique) à ce paramètre empirique, au mécanisme de réduction lui-même, ainsi qu'aux propriétés structurales de l'échantillon et à la manière dont ces propriétés évoluent au cours de la réduction. L'ensemble de ces informations a ensuite été traduit dans un modèle thermodynamique de réduction des argiles, permettant d'identifier les données nécessaires (disponibles et à acquérir) à l'établissement d'un modèle contraint par les informations structurales. / Iron plays a key role in many biogeochemical processes implying electron transfers (i.e. redox reactions).Clays form a family of ubiquitous minerals; some contain iron in their structure. Clay structure provides specific properties to this structural iron (Festr). A constantly growing set of studies focuses on Festr redox properties, interesting various research fields, such as agronomic study on soil's nutriments accessibility or organic matter growth, or even studies on heavy metals and radionuclides retention in clay barrier. Study on Festr redox properties remains however challenging. Clay' crystallographic structure rules Festr redox properties, but in return, Festr redox transformation has impact on this structure. The redox history of the clay (i.e. extent and number of prior redox cycles) influences both Festr redox properties and the way they evolve upon redox processes. Given the number and complexity of implied mechanisms, and given the variety of clay structures, this PhD thesis focuses on the particular group of dioctahedral smectites, more precisely on the iron rich end-members named nontronites and on the impact of Festr reduction on their structural properties. The studied reduction mechanism is itself restricted to reduction by powerful chemical reduces such as dithionite. Along with a critical review of available abundant literature on this specific aspect, experimental works have been conducted and several theoretical approaches have been discussed and developed to construct a structural model of Festr redox properties and their relations with the smectitic structure. New measures of clay negative layer charge as a function of reduction level done during this PhD clearly indicate, contrary to previously assumed behavior, negative layer charge do not monotonously increases upon Festr reduction, but shows a dramatic drop starting from a given reduction level. The reduction domain of a nontronite is thus spitted into two domains: the first is characterized by a negative layer charge increase and reversible structural changes; the second is characterized by a drop of the negative layer charge and less or even not reversible structural transformations. The models developed, during this PhD, are restricted to the first reduction sequence, i.e. the reversible one. A first empiric model allows modeling nontronite CEC changes from their unit-cell formula (which provides composition and charge) and using an empirical parameter which is common to a series of low tetrahedral-Fe-bearing nontronites for which experimental data are available. In a second approach, an algorithm simulating how Festr reduction progresses has been set up, allowing to link negative layer change of particular type of nontronites (tetrahedral-Fe-poor) to this empirical parameter, to the reduction mechanism itself, and to the structural properties of the sample and the way they evolve upon reduction. Following this, the whole of this set of information has been implemented in a thermodynamic model of Fetr reduction, making it possible to identify the required data (available or to acquire) for the establishment of a model constrained by structural information.

Submitted by Hugo Tadashi Kano null (tada_tk@aluno.ibb.unesp.br) on 2018-03-15T12:00:25Z No. of bitstreams: 1 Dissertação Mestrado - Hugo Tadashi Kano.pdf: 1976397 bytes, checksum: 22cf9f00e7caf878327b4634bb6d02ad (MD5) / Approved for entry into archive by Luciana Pizzani null (luciana@btu.unesp.br) on 2018-03-19T12:53:29Z (GMT) No. of bitstreams: 1 kano_ht_me-bot.pdf: 1976397 bytes, checksum: 22cf9f00e7caf878327b4634bb6d02ad (MD5) / Made available in DSpace on 2018-03-19T12:53:29Z (GMT). No. of bitstreams: 1 kano_ht_me-bot.pdf: 1976397 bytes, checksum: 22cf9f00e7caf878327b4634bb6d02ad (MD5) Previous issue date: 2018-02-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A prevalência mundial de Síndrome Metabólica (SM) está aumentando drasticamente nos últimos anos. Esta desordem consiste de um conjunto de condições metabólicas, contemplando hiperadiposidade abdominal, resistência insulínica (RI), dislipidemia e hipertensão, e é fator de risco para o desenvolvimento de Diabetes Mellitus tipo 2 (DM2) e doenças cardiovasculares (DCVs). Muitos estudos indicam a participação do estresse oxidativo (EO) junto com o estado estresse inflamatório (EI) como parte do desenvolvimento e agravamento da SM e surgimento das doenças crônicas não-transmissíveis (DCNTs). O EO é caracterizado como estado de desequilíbrio entre os sistemas oxidativo e antioxidante, resultando no excesso de espécies reativas de oxigênio (EROs), menor capacidade antioxidante e efeitos deletérios a tecidos e células. A regulação das reações de oxidação e redução são importantes para o controle de funções fisiológicas e combate ao estresse. Diante disso, os aminotióis ou compostos tio-redox (homocisteína, cisteína e glutationa) exercem importante papel no equilíbrio do estado redox celular. Neste artigo de revisão, analisamos os aspectos fisiopatológicos de compostos tio-redox no curso da SM. / The worldwide prevalence of Metabolic Syndrome (MetS) has been increasing dramatically in recent years. MetS is a set of metabolic conditions, including abdominal hyperadiposity, insulin resistance, dyslipidemia and hypertension, and is a risk factor for the development of type 2 diabetes mellitus and cardiovascular diseases. Many studies indicate the participation of oxidative stress along with the pro-inflammatory state as part of the development and aggravation of MetS and emergence of chronic noncommunicable diseases. Oxidative stress is characterized as a state of imbalance between oxidative and antioxidant systems, resulting in excess of reactive oxygen species, lower antioxidant capacity and deleterious effects on tissues and cells. The regulation of the oxidation and reduction reactions are important for the control of physiological functions and the fight against stress. In view of this, the aminothiols or thiol-redox compounds (homocysteine, cysteine and glutathione) play an important role in the equilibrium of the cellular redox state. In this review article, we analyze the pathophysiological aspects of thiol-redox compounds in the course of MetS.