Estudos pré-clínicos da ação anti-Alzheimer do octilseleno-xilofuranosídeo

Abstract

Alzheimer's disease is a multifactorial disease, characterized by progressive neurodegeneration, with a pathophysiology not yet fully elucidated. In this sense, different theories have been developed aiming to explain how this pathological process works. In the present study, some of these aspects were evaluated, such as the amyloidogenic and cholinergic pathways, monoaminergic neurotransmission, oxidative stress and behavioral alterations related to cognition and memory formation, aiming to evaluate the protective action of the octylselenoxylofuranoside (OSX). To achieve these objectives, OSX was administered orally at a dose of 0.1 mg/kg during the first 20 days of the experimental design. After pretreatment with the compound, mice underwent intracerebroventricular injection of streptozotocin (two doses of 1.5 mg/kg, in the 21st and 23rd days), as an Alzheimer-like model. 15 days after the last injection, behavioral tests evaluating memory formation and cognition were performed. After behavioral tests, animals underwent euthanasia to collect the brain for evaluation of markers of oxidative stress, kinetic activity of the enzymes acetylcholinesterase and monoamine oxidase, and evaluation of the amyloidogenic pathway by qRT-PCR. The results showed that OSX protected mice from abnormalities caused by the behavioral pattern in different types of memory. In addition, OSX protected against increased levels of lipid peroxidation, inhibited acetylcholinesterase and monoamine oxidase enzymes, and reduced the relative expression of APP, β and γ-secretase, main points of amiloidogenic pathway. Overall, OSX presented anti-Alzheimer's abilities, protecting the mice from changes induced by streptozotocin, in different parameters of the disease.