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Effect of Thiazolidin-4-one Against Lipopolysaccharide-Induced Oxidative Damage, and Alterations in Adenine Nucleotide Hydrolysis and Acetylcholinesterase Activity in Cultured Astrocytes.

Authors
  • Alvez, Fernando Lopez1
  • Bona, Natália Pontes2
  • Pedra, Nathalia Stark1
  • da Silva, Daniel Schuch3
  • Cunico, Wilson João3
  • Stefanello, Francieli Moro2
  • de Andrade, Cinthia Melazzo4
  • Soares, Mayara Sandrielly Pereira1
  • Spanevello, Roselia Maria5, 6
  • 1 Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Neuroquímica, Inflamação e Câncer, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário S/N, Pelotas, RS, Brazil. , (Brazil)
  • 2 Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Biomarcadores, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário S/N, Pelotas, RS, Brazil. , (Brazil)
  • 3 Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Química Aplicada a Bioativos, Centro Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, RS, Brazil. , (Brazil)
  • 4 Programa de Pós-Graduação em Medicina Veterinária, Departamento de Clínica de Pequenos Animais, Laboratório de Análises Clínicas Veterinária, Hospital Veterinário, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. , (Brazil)
  • 5 Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Neuroquímica, Inflamação e Câncer, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário S/N, Pelotas, RS, Brazil. [email protected]. , (Brazil)
  • 6 Universidade Federal de Pelotas, Campus Capão do Leão, s/n, Caixa Postal 354, Pelotas, RS, CEP 9601090, Brazil. [email protected]. , (Brazil)
Type
Published Article
Journal
Cellular and Molecular Neurobiology
Publisher
Springer-Verlag
Publication Date
Jan 01, 2023
Volume
43
Issue
1
Pages
283–297
Identifiers
DOI: 10.1007/s10571-021-01177-1
PMID: 35031909
Source
Medline
Keywords
Language
English
License
Unknown

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. © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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