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Doctoral Thesis
DOI
https://doi.org/10.11606/T.46.2016.tde-26082016-150838
Document
Author
Full name
Leandro Giavarotti
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2004
Supervisor
Committee
Junqueira, Virginia Berlanga Campos (President)
Abdalla, Dulcineia Saes Parra
Dias Neto, Emmanuel
Mariano, Mario
Salomão, Reinaldo
Title in Portuguese
Monócitos como indicadores de atividade inflamatória e oxidativa em idosos em déficit cognitivo e com doença de Alzheimer
Keywords in Portuguese
Antioxidantes
Doença de Alzheimer (Estudo)
Doença de Alzheimer (Prevenção e controle)
Estresse oxidativo (Efeitos adversos)
Inflamação (Efeitos adversos)
Abstract in Portuguese
A Doença de Alzheimer é uma doença neurodegenerativa progressiva e de início tardio, que compromete principalmente as areas da cognição, julgamento e estabilidade emocional. Esta doença se caracteriza por dois tipos de lesões cerebrais características: emaranhados neurofibrilares e placas senis. Os emaranhados neurofibrilares são compostos por uma proteína do citoesqueleto (proteína tau) hiperfosforilada e agregada. As placas senis são formadas por agregados da proteína β-amilóide. A doença de Alzheimer é resultado dainteração de vários fatores ainda incompletamente elucidados; não obstante, o estresse oxidativo e os processos inflamatórios ocupam posição de destaque dentre esses fatores. Neste trabalho, avaliamos as atividades das enzimas eritrocitárias superóxido dismutase, catalase e glutationa peroxidase, assim como o conteúdo plasmático de glutationa total, vitamina C, α-tocoferol, β-caroteno, licopeno e coenzima Q10. A esses parâmetros antioxidantes foram contrapostas medidas de oxidação de lipídios e proteínas plasmáticas. Adicionalmente, efetuamos a avaliação das expressões monocitárias de HLADR e CD-11b, e das citocinas IL-6, IL-1α e TNF-α. Nossos resultados mostram que os pacientes de doença de Alzheimer possuem níveis circulantes de atocoferol inferiores aos pacientes controles, e possuem monócitos que apresentam maior expressão basal de HLA-DR e maior produção de IL-1α quando estimulados por LPS. Esses resultados fortalecem a hipótese inflamatória na doença de Alzheimer, de acordo com trabalhos recentes que apontam bons resultados com o a-tocoferol na sua prevenção e tratamento.
Title in English
Monocytes as inflammatory and oxidative activity indicators in elderly people without cognitive impairment and Alzheimer's disease
Keywords in English
Alzheimer\'s disease (Prevention and control)
Alzheimer\'s disease (Study)
Antioxidants
Inflammation (adverse effects)
Oxidative stress (Adverse effects)
Abstract in English
Alzheimer's disease is a late-onset, progressive degenerative disease that affects mainly the judgement, emotional stability and memory domains. This disease is characterized by two telltale cerebral lesions: neurofibrillary tangles and senile plaques. Neurofibrillary tangles are constituted by hyperphosphorylated cytoskeleton protein tau aggregates, while senile plaques are mainly composed by β-amyloid protein aggregates. Alzheimer's disease is the outcome of a complex interaction among several factors which are not fully understood yet; nevertheless it is clear thar oxidative stress and inflammatory pathways rate high among these factors. In this work, we evaluated the erythrocytic acitivities of superoxide dismutase, catalase and glutathione peroxidase, as well as the plasma levels of total glutathione, α-tocopherol, α-carotene, lycopene, and coenzyme Q10. These antioxidant parameters were confronted with plasmatic levels of protein and lipid oxidation products. Additionally, we measured the basal expression of monocyte HLA-DR and CD-11b, as well as the monocyte production of the cytokines IL1-α, IL-6 and TNF-α. Our results show that Alzheimer's Disease patients show lower plasmatic levels of α-tocopherol when compared to control patients, and have higher basal monocyte HLA-DR expression associated with higher IL-1α production when stimulated by LPS. These results lend support to the inflammatory theory of Alzheimer's disease, according to recent works that indicate good results of α-tocopherol administration in both its prevention and treatment.
 
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Publishing Date
2016-08-26
 
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