Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Honey is a complex product produced by honeybees from nectar, being widely used for its sweetening properties, as well as for its benefits to human health. Honey presents anti-inflammatory, hypoglycemic and antioxidant properties. Hypoxia followed by reperfusion is a condition triggered in several pathologies and can culminate with oxidative tissue damage. The fruit-fly, Drosophila melanogaster, has hypoxia tolerant characteristics and homology with vertebrate from pathways involved in the cascade of cellular responses for hypoxia/reperfusion. Considering these aspects, the main objective of this work was to evaluate the possible protective effect of honey produced in the Brazilian Pampa Biome on changes induced by hypoxia/reperfusion in Drosophila melanogaster, with emphasis on oxidative stress. Wild flies were treated with a diet containing 10% honey for 3 days and subsequently submitted to hypoxia conditions (3hs). After reperfusion of oxygen, parameters of survival, behavior, oxidative stress as well as mRNA expression of genes related with metabolic, inflammation and death pathways were evaluated. The results demonstrated that the honey tested is composed of compounds with antioxidant activity that were recognized both in vitro and in vivo. Hypoxia/reperfusion induced an increase in the regulation of mRNA expression of Sima (HIF-1), NFκB, Nrf2, HOX, AKT-1, INR, dILP2, dILP5 and HSP27. Indeed, flies submitted to hypoxia/reperfusion has a expression decreased of EWG and Opa-1. Honey was able to reestablish the expression of Opa-1, a gene related to mitochondrial fusion. Honey treatment also reduced the changes induced by hypoxia/reperfusion in parameters of survival, locomotor deficits, wing position, reactive oxygen species (ROS) production, GST, caspases and mitochondrial complex I activities. The results obtained here show, for the first time, the beneficial effects of honey against changes induced by hypoxia/reperfusion in Drosophila melanogaster. This study evidenced that that the honey from the Brazilian Pampa Biome has a high quality and a significant antioxidant activity in vivo, which can be related with its beneficial effects against hypoxia/reperfusion. In addition, we consider the honey as well as Drosophila melanogaster promising targets for studying pathologies associated with oxidative stress and hypoxia/reperfusion. / O mel é um produto complexo produzido por abelhas melíferas a partir do néctar e bastante utilizado pelas suas propriedades edulcorantes, bem como pelos seus benefícios para a saúde humana. O mel apresenta atividades anti-inflamatória, hipoglicêmica e antioxidante. A hipóxia seguida de reperfusão é uma condição desencadeada em diversas patologias e pode culminar com danos teciduais de cunho oxidativo. A mosca-da-fruta, Drosophila melanogaster, possui características tolerantes a hipóxia e homologia com animais vertebrados de vias envolvidas na cascata de respostas celulares à hipoxia/reperfusão. Considerando tais aspectos, o objetivo principal desse trabalho foi avaliar os efeitos do mel produzido no Bioma Pampa Brasileiro sobre as alterações teciduais/moleculares induzidas por hipóxia/reperfusão em Drosophila melanogaster, com ênfase em estresse oxidativo. Moscas selvagens foram tratadas com 10% de mel por 3 dias e posteriormente submetidas à hipóxia (3hs). Após reperfusão de oxigênio, foram avaliados parâmetros de sobrevivência e comportamento; parâmetros de estresse oxidativo, bem como, a expressão de mRNA de genes envolvidos em vias metabólicas, inflamatórias e morte celular. Os resultados demonstraram que o mel testado é constituído de compostos com atividade antioxidante, que foi reconhecida tanto in vitro como in vivo. A hipóxia/reperfusão induziu um aumento na expressão do mRNA de Sima (HIF-1), LDH, NFκB, Nrf2, HOX, AKT-1, INR, dILP2, dILP5 e HSP27. As moscas submetidas a hipoxia/reperfusão também apresentaram expressão diminuída do mRNA do EWG e Opa-1. O mel foi efetivo em restabelecer a expressão alterada de Opa-1, gene relacionado com fusão mitocondrial. Além disso, o tratamento com mel reduziu as alterações induzidas por hipóxia/reperfusão sobre os parâmetros de sobrevivência, déficits locomotores, alteração da posição das asas, produção de espécies reativas de oxigênio (EROs), atividades da GST, caspases e complexo I da cadeia respiratória mitocondrial. Os resultados obtidos aqui mostram, pela primeira vez, os efeitos benéficos de mel contra alterações induzidas por hipóxia/reperfusão em Drosophila melanogaster. Este estudo evidenciou que o mel do Bioma Pampa Brasileiro tem além de um alto nível de qualidade, uma atividade antioxidante significativa in vivo, a qual pode estar relacionada com seus efeitos benéficos contra hipoxia/reperfusão. Com base nos resultados, considera-se ainda tanto o mel como a Drosophila melanogaster alvos promissores para estudos voltados para doenças associadas com condições de estresse e hipoxia/reperfusão.

Cardiovascular diseases represent the most important health risk factors because they are responsible for more than 50% of total mortality. Among them, the ischemic heart disease is leading cause of mortality. From the whole spectrum of different cardioprotective phenomena we have selected: 1) adaptation to chronic normobaric hypoxia (CNH) as the traditional experimental model in our laboratory area and 2) protective effect of exercise which in recent years represents promising and clinically relevant protective mechanism. The whole thesis is based on two studies. Aim of the first study was to characterize the expression of the main pro-inflammatory cytokine, TNF-α, in hearts of rats adapted to CNH. Chronic TNF-α inhibition by infliximab was used for discovering of certain role of TNF-α in CNH. We showed that increased myocardial level of TNF-α during adaptation to CNH was contributed via its receptor TNFR2 and nuclear factor κB-dependent activation of protective redox signalling with increased antioxidant defence. This adaptive pathway participates on the infarct size-limiting effect of CNH. Aim of the second study was find out whether exercise training and CNH could play synergy in cardiac protection in rats model. We reported that CNH and exercise reduced infarct size but their combination...