Estudo do efeito de Dimetil fumarato sobre a disfunção cerebral após sepse experimental em ratos

Introduction: Sepsis is dysfunction of organs with life-threatening potential caused by a dysregulated host response to infection. Sepsis is often associated with acute central nervous system (CNS) - Sepsis Associated Encephalopathy (EAS) dysfunction, with the primary level of consciousness being altered. Dimethyl fumarate (DMF) has been shown to be an important target for CNS changes due to inflammatory response or reactive oxygen species (ROS). Objective: to evaluate the effect of DMF on brain dysfunction after experimental sepsis in rats. Methods: Male Wistar rats (250-350g) were submitted to the CLP model, with sham as control. The groups were divided into sham + vehicle; Sham + NAC; Sham + DMF; CLP + vehicle; CLP + NAC and CLP + DMF. The animals were treated with DMF (15 mg/kg dissolved in 0.08% dimethylsulfoxide in 0 hours and 12 hours after CLP per gavage) and administration of n-acetylcysteine (NAC) (20mg/kg, 3, 6 and 12 hours after CLP Via subcutaneous) as control. In the 24 hours after CLP, the cytokines, myeloperoxidase (MPO), nitrite/nitrate (N/N), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were analyzed in cortex, pre-frontal cortex and hippocampus samples and oxidative damage in lipids and proteins. Data analyzed by ANOVA and Tukey post hoc with p <0.05. Results: We verified an increase in the level of cytokines, MPO, N / N, oxidative damage lipids and proteins, and increased activity of SOD and GPx enzymes in the different structures studied, when the animals were submitted to sepsis and treatment with DMF was effective in reversion These parameters. Conclusion: DMF treatment was effective in reversing parameters related to inflammation and oxidative stress in the brains of rats submitted to sepsis.Introdução: A sepse é a disfunção de órgãos com potencial risco de vida causada por uma resposta desregulada do hospedeiro frente à infecção. A sepse é frequentemente associada com a disfunção aguda do Sistema Nervoso Central (SNC) - Encefalopatia Associada à Sepse (EAS), possuindo como principal sinal clínico o nível de consciência alterado. O dimetil fumarato (DMF), tem se mostrado um importante alvo para alterações no SNC decorrentes da resposta inflamatória ou das espécies reativas de oxigênio (EROs). Objetivo: avaliar o efeito de DMF sobre a disfunção cerebral após sepse experimental em ratos. Métodos: ratos Wistar machos (250-350g) foram submetidos ao modelo CLP, com sham como controle. Os grupos foram divididos em sham+veículo; sham+NAC; sham+DMF; CLP+veículo; CLP+NAC e CLP+DMF. Os animais foram tratados com DMF na dose de (15 mg/kg dissolvido em 0.08% de dimetilsulfóxido em 0 horas e 12 horas após CLP por gavagem) e administração de n-acetilcisteína (NAC) (20mg/kg, 3, 6 e 12 horas após CLP via subcutânea) como controle. Em 24 horas após CLP, nas amostras de córtex, córtex pré-frontal e hipocampo, foram realizadas análises de citocinas, mieloperoxidase (MPO), nitrito/nitrato (N/N), superóxido dismutase (SOD), catalase (CAT), glutationa peroxidade (GPx) e dano oxidativo em lipídios e proteínas. Dados analisados por ANOVA e post hoc Tukey com p