Dietary fish oil increases catalase activity in patients with probable Alzheimer's disease / El aceite de pescado en la dieta aumenta la actividad de la catalasa en pacientes con probable enfermedad de Alzheimer

Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of neuritic plaques and neurofibrillary tangles that finally result in synaptic and neuronal loss. Oxidative stress accompanies pathological changes in AD. Objective: to assess the efficacy of dietary omega 3 polyunsaturated fatty acids supplementation on the levels of proteins oxidation, hydroperoxides and enzymatic activities of catalase and superoxide dismutase in AD patients. Methods: clinical, controlled, randomized, double-blind trial. Patients consumed fish oil or placebo for one year. Oxidative stress markers were assessed in plasma using spectrophotometric methods. Results: carbonyl groups in proteins and hydroperoxides in plasma have similar values in both treatment groups at the beginning of the study. At six and 12 months of treatment, these values decreased significantly in the fish oil group, while in the placebo group no changes were observed in both oxidative stress markers. Catalase activity increased significantly at six and twelve months after treatment in patients treated with fish oil. While the superoxide dismutase activity was not modified in both study groups. Conclusions: patients who consume omega 3 polyunsaturated fatty acids at a stable dose of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) show decreased oxidation of proteins and lipids in plasma. In addition, an increase in catalase activity was detected. Thus, the presented data warrants further studies evaluating the antioxidant effect of omega 3 polyunsaturated fatty acids. (AU)

Antecedentes: la enfermedad de Alzheimer (EA) es un trastorno neurodegenerativo caracterizado por la presencia de placas neuríticas y ovillos neurofibrilares que finalmente resultan en pérdida sináptica y neuronal. El estrés oxidativo acompaña los cambios patológicos en la EA. Objetivo: evaluar la eficacia de la suplementación dietética con ácidos grasos poliinsaturados omega 3 sobre los niveles de oxidación de proteínas, hidroperóxidos y actividades enzimáticas de catalasa y superóxido dismutasa en pacientes con EA. Métodos: ensayo clínico, controlado, aleatorizado, doble ciego. Los pacientes consumieron aceite de pescado o placebo durante un año. Los marcadores de estrés oxidativo se evaluaron en plasma mediante métodos espectrofotométricos. Resultados: los grupos carbonilo en proteínas e hidroperóxidos en plasma tuvieron valores similares en ambos grupos de tratamiento al inicio del estudio. A los seis y 12 meses de tratamiento estos valores disminuyeron significativamente en el grupo de aceite de pescado, mientras que en el grupo placebo no se observaron cambios en ambos marcadores. La actividad de catalasa aumentó significativamente a los seis y doce meses después del tratamiento en pacientes tratados con aceite de pescado; sin embargo, la actividad superóxido dismutasa no se modificó en ambos grupos de estudio. Conclusiones: los pacientes que consumieron los ácidos grasos poliinsaturados omega 3 a una dosis estable de ácido docosahexaenoico (DHA) y ácido eicosapentaenoico (EPA) muestran una oxidación reducida de proteínas y lípidos en plasma. Además, se detectó un aumento en la actividad de la catalasa. Por tanto, los datos presentados justifican más estudios que evalúen el efecto antioxidante de dichos ácidos grasos. (AU)

Cognitive disorder and dementia in type 2 diabetes mellitus.

Insulin, a key pleiotropic hormone, regulates metabolism through several signaling pathways in target tissues including skeletal muscle, liver, and brain. In the brain, insulin modulates learning and memory, and impaired insulin signaling is associated with metabolic dysregulation and neurodegenerative diseases. At the receptor level, in aging and Alzheimer's disease (AD) models, the amount of insulin receptors and their functions are decreased. Clinical and animal model studies suggest that memory improvements are due to changes in insulin levels. Furthermore, diabetes mellitus (DM) and insulin resistance are associated with age-related cognitive decline, increased levels of ß-amyloid peptide, phosphorylation of tau protein; oxidative stress, pro-inflammatory cytokine production, and dyslipidemia. Recent evidence shows that deleting brain insulin receptors leads to mild obesity and insulin resistance without influencing brain size and apoptosis development. Conversely, deleting insulin-like growth factor 1 receptor (IGF-1R) affects brain size and development, and contributes to behavior changes. Insulin is synthesized locally in the brain and is released from the neurons. Here, we reviewed proposed pathophysiological hypotheses to explain increased risk of dementia in the presence of DM. Regardless of the exact sequence of events leading to neurodegeneration, there is strong evidence that mitochondrial dysfunction plays a key role in AD and DM. A triple transgenic mouse model of AD showed mitochondrial dysfunction, oxidative stress, and loss of synaptic integrity. These alterations are comparable to those induced in wild-type mice treated with sucrose, which is consistent with the proposal that mitochondrial alterations are associated with DM and contribute to AD development. Alterations in insulin/IGF-1 signaling in DM could lead to mitochondrial dysfunction and low antioxidant capacity of the cell. Thus, insulin/IGF-1 signaling is important for increased neural processing and systemic metabolism, and could be a specific target for therapeutic strategies to decrease alterations associated with age-related cognitive decline.