Efeitos do resveratrol na sinalização purinérgica em camundongos expostos ao alumínio

Abstract

Aluminum (Al) is a compound found in nature, and is widely used industrially, which means that humans are exposed to it daily. Due to its ability to cross the blood-brain barrier, it can accumulate in the brain in regions of the hippocampus and cortex, which is why it has been associated with neurodegeneration. Previous studies suggest that combined with citrate (CIT), its absorption and, therefore, its toxic effects are increased, favoring the emergence of pathologies such as Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder that leads to gradual memory loss. The relationship between Al and purinergic neurotransmission is recent, which is why it is necessary to study alternative methods that can act to protect against possible pathological states. The use of natural substances with antioxidant properties has stood out, in this context, resveratrol (RSV) has a widely reported anti-inflammatory capacity, in addition to being a potent activator of the Sirtuin family, having been used as an antioxidant and neuroprotector when it comes to FROM THE. Its neuroprotection mechanism has not yet been fully elucidated, therefore, the study of purinergic and oxidant/antioxidant signaling becomes essential. In this study, 60 male Swiss mice were divided into 6 groups (Control, CIT, RSV, Al, Al+CIT and Al+RSV) and treated for 30 days, every 48 hours. Through behavioral analyzes (Open field test, Object recognition and Y maze), it was possible to identify the reduction of short and medium-term memory in Swiss mice intoxicated with Al, as well as the increase in anxiety in these mice. It was also possible to observe the protective effects of RSV against Al intoxication, both in reducing anxiety and improving memory in mice. Enzymatic analyzes (NTPDase, 5'-NT and ADA) showed the inflammatory activity triggered by Al, through increased ATP hydrolysis in the intoxicated group, while RSV had an anti-inflammatory effect, reducing the hydrolysis of this nucleotide. In the case of ADA, we also observed a positive modulation of the activity of this enzyme in the inflammatory mechanism triggered by Al, as well as the neuroprotection exerted by RSV. Western Blot analyzes (A1, A2A, P2X7, NRLP3 and BDNF) confirmed the involvement of Al in the inflammatory mechanisms related to AD pathology and the neuroprotection exerted by RSV in these receptors. With this study, we concluded that Al acts by triggering inflammatory processes in the body of mice, impairing memory and causing severe anxiogenic states, and RSV has the ability to remedy these damages caused by Al, acting as a neuroprotector, improving the memory of mice and reducing inflammatory activities.