Estudo pré-clínico com utilização de nutracêuticos sobre a disfunção cerebral na sepse

• Ano de defesa: 2018
• Autor(a) principal: Della Giustina, Amanda
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Óleo de peixe; Ácido lipoico; Cognição; Neuroinflamação; Antioxidante; Comportamento
• Link de acesso: https://repositorio.animaeducacao.com.br/handle/ANIMA/3094

Introduction: Sepsis is a severe organic infection-related dysfunction that impacts the normal regulation of several organ systems, including the central nervous system (CNS). The inflammation and oxidative stress play crucial roles in the development of brain dysfunction in sepsis. Objective: To determine the effect of a α-lipoic acid (ALA) plus fish oil (FO)-association as an important antioxidant and anti-inflammatory approach on brain dysfunction in septic rats. Methods: For in vitro assay, microglia cells were stimulated with LPS alone or added with ALA, FO or the association of ALA+FO (Assoc) and cytokines were measured at 24 h later. For in vivo assay, Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) or sham (control) and treated orally with vehicle (saline; sal), ALA, FO, or the association (Assoc). Animals were divided into Sham+sal, Sham+FO, Sham+ALA, CLP+sal, CLP+FO, CLP+ALA and CLP+Assoc groups. At 24 h and 10 days after surgery, the hippocampus, prefrontal cortex and total cortex were obtained and assayed for levels of TNF-α, IL-1β and IL-10, blood brain barrier (BBB) permeability, nitrite/nitrate concentration, myeloperoxidase (MPO) activity, thiobarbituric acid reactive species (TBARS) formation, protein carbonyls, superoxide dismutase (SOD) and catalase (CAT) activity, NGF and BDNF levels. Behavioral tasks were performed 10 days after surgery. Results: The association of ALA+FO reduced the levels of TNF-α and MPO in the total cortex, decreased IL-1β levels in the prefrontal cortex and hippocampus and diminished protein carbonylation in all brain structures. ALA+FO enhanced BDNF levels and CAT activity in all brain structures and prevented memory and learning impairment. Conclusion: Our findings indicate that the association of ALA+FO diminishes the negative impact of polymicromial sepsis in the rat brain by reducing inflammatory and oxidative stress markers and preventing long-term cognitive damage.