Associação entre o consumo de antocianinas e a prevenção de alterações cognitivas, neuroquímicas e inflamatórias nos modelos experimentais de desmielinização e de neuroinflamação em roedores

Abstract

Anthocyanins (ANT) are phytonutrients with antioxidant and neuroprotective properties. In this context, this study sought evidence of a possible protective effect of ANT on models of demyelination and neuroinflammation in rodents. Rats were submitted to the experimental demyelination by ethidium bromide injection (EB, 0.1% in saline, 10 μL) in the pons. In addition, an in vitro experiment was conducted to check whether ANT (1-100 μg/mL) are able to reduce the oxidative and nitrosative stress in pons of rats exposed to hydrogen peroxide (H2O2, 4 mM) and sodium nitroprusside (NPS, 1 mM). C57BL6 mice were subjected to neuroinflammation by acute administration lipopolysaccharide (LPS 250 μg/kg, 5 mL/kg, in saline) intraperitoneally. ANT doses in both protocols were 30 and 100 mg/kg (via oral by gavage, vehicle saline). The ANT were able to neutralize the reactive species induced by H2O2 and by NPS reducing the malondialdehyde, protein carbonyl and nitrites and nitrates (NOx) contents. In relation to the model of toxic demyelination, ANT obtained from grape skins were administered during 7 days from the BE injection. On the seventh day the animals were euthanized. It can be seen a protective effect of ANT on the increase in oxidative stress markers: malondialdehyde, carbonyl protein and NOx levels. ANT also protected the reduction in superoxide dismutase activity and the NPSH / GSH content. A negative correlation showed an increase in markers of oxidative stress and the reduction in activity of the enzymes Na+, K+-ATPase and Ca2+-ATPase. ANT restored the activity of ions pumps. In parallel, ANT reduced the increase in interleukin (IL)-1β, IL-6, tumoral necrosis factor (TNF)-α and interferon (INF)-γ induced by the EB. ANT suppressed the local inflammatory infiltrate, the presence of neutrophils and reduced demyelination area. In relation to neuroinflammation model, the pretreatment ten days with ANT from blueberry prevented the memory loss induced by LPS administered post-training. ANT also prevented the increased in the malondialdehyde, carbonyl protein and NOx levels 4 and 24 hours post-LPS administration in the cerebral cortex and hippocampus. ANT not prevented the reduction in the Na+, K+-ATPase activity but were able to suppress the neutrophil infiltration and microglial immunoreactivity in the hippocampus 24 hours after LPS administration. The neuroinflammation and demyelination were not able to induce significant neuronal death but alter the morphology of these cells. ANT were able to prevent this effect. These results suggest that ANT can act as adjuvants in the treatment of diseases characterized by neuroinflammation and demyelination episodes, among them stands out Multiple Sclerosis.