Efeito do composto 3-(3-(dietilamino)propil)-2-(4-(metiltio)fenil)tiazolidin-4-ona em parâmetros neuroinflamatórios em cultura primária de astrócitos de ratos expostas ao lipolissacarídeo

Abstract

Astrocytes have multiple important roles associated with brain physiology. However, depending of the stimuli, astrocyte may exacerbate inflammatory reactions leading to developmental and progression of neurological diseases. In this line, therapies targeting astrocytes represent a promising area to development of new brain drugs. Thiazolidinones are heterocyclic compounds that have a sulphur and nitrogen atom and a carbonyl group in the ring and represent a class of compounds of great scientific interest due to their pharmacological properties. The aim of this study was to investigate the glioprotective effect the compound 3-(3-(dietilamino)propil)-2-(4-(metiltio)fenil)tiazolidin-4-ona (DS27) in cell proliferation and morphology, oxidative stress parameters, activity of the enzymes ectonucleotidases and acetylcholinesterase (AChE) and interleukin 6 (IL-6) levels in primary astrocytes culture submitted to a model of neuroinflammation induced by lipopolysaccharide (LPS). The astrocytes culture was exposed to LPS (10 μg/ml) for 3 h and subsequently treated with compound DS27 for 24 and 48 h (concentrations ranging to 10-100 μM). LPS induced an increase in astrocytes proliferation, AChE activity, IL-6 levels, oxidative damage, and an increase in ATP and ADP and reduction in AMP hydrolysis in rat primary astrocytes cultures. DS27 treatment was effective in to protect these alterations induced by LPS in astrocytes cells. Our findings demonstrated that DS27 is able to modulate cholinergic and purinergic signaling, redox status and pro inflammatory cytokines in LPS induced astrocyte damage. These glioprotective effects of DS27 compound may be very important to improve neuroinflammation, which is associated with many brain diseases.