Abstract
Astrocytes play multiple important roles in brain physiology. However, depending on the stimuli, astrocytes may exacerbate inflammatory reactions, contributing to the development and progression of neurological diseases. Therefore, therapies targeting astrocytes represent a promising area for the development of new brain drugs. Thiazolidinones are heterocyclic compounds that have a sulfur 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 effect of 3-(3-(diethylamino)propyl)-2-(4-(methylthio)phenyl)thiazolidin-4-one (DS27) on cell proliferation and morphology, oxidative stress parameters, activity of the enzymes ectonucleotidases and acetylcholinesterase (AChE) and interleukin 6 (IL-6) levels in primary astrocyte cultures treated with lipopolysaccharide (LPS), to model neuroinflammation. The astrocyte 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 astrocyte proliferation, AChE activity, IL-6 levels, oxidative damage, ATP and ADP and a reduction in AMP hydrolysis in rat primary astrocyte cultures. DS27 treatment was effective in reversing these alterations induced by LPS. Our findings demonstrated that DS27 is able to modulate cholinergic and purinergic signaling, redox status, and the levels of pro-inflammatory cytokines in LPS-induced astrocyte damage. These glioprotective effects of DS27 may be very important for improving neuroinflammation, which is associated with many brain diseases.
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Acknowledgements
The authors acknowledge the Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Rio Grande do Sul. This study was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil (CAPES—Finance code 001). R.M.S, W.C., F.M.S and C.M.A are recipients of the CNPq fellowship.
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FLA: Astrocyte culture and treatment, biochemical analysis, statistical analysis, discussion, and manuscript preparation. NPB and NSP: Astrocyte treatment and oxidative stress analysis. DSS and WC: DS27 design and synthesis. FMS, MSPS, CMA: Results interpretation and manuscript preparation. RS: Experimental design, results analysis and manuscript preparation. RS, CMA, WC: Financial support.
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Alvez, F.L., Bona, N.P., Pedra, N.S. et al. Effect of Thiazolidin-4-one Against Lipopolysaccharide—Induced Oxidative Damage, and Alterations in Adenine Nucleotide Hydrolysis and Acetylcholinesterase Activity in Cultured Astrocytes. Cell Mol Neurobiol 43, 283–297 (2023). https://doi.org/10.1007/s10571-021-01177-1
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DOI: https://doi.org/10.1007/s10571-021-01177-1