Abstract
Manganese (Mn) is an essential metal for many functions in the body. However, in excess, it can be neurotoxic and cause a Parkinson-like syndrome, known as manganism. Here, we aimed to identify a protective effect of probucol, a lipid-lowering agent with anti-inflammatory and antioxidant properties, against Mn-induced toxicity in human neuroblastoma (SH-SY5Y) and glioblastoma (C6) cell lines. The cells were incubated with increasing concentrations of Mn followed by probucol addition 1, 3, 6, and/or 24 h to assess the metal toxic doses and measure the protective effect of probucol against Mn-induced oxidative damage. Longer exposition to Mn showed decreased SH-SY5Y cellular viability in concentrations higher than 100 µM, and probucol was able to prevent this effect. The C6 cells were more sensitive to the Mn deleterious actions, decreasing the cell viability after 6 h of 500 µM Mn exposure. In addition, probucol prevents the complex I and II of the mitochondrial respiratory chain (MRC) inhibition caused by Mn and decreased the intracellular ROS production. Taken together, our results showed that Mn toxicity affects differently both cell lines and probucol has a protective effect against the oxidative imbalance in the central nervous system.
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Acknowledgements
The authors also are grateful to a native speaker that revised manuscript Mr. Samuel Patterson from University of Southampton.
Funding
The authors are grateful to the Universidade do Oeste de Santa Catarina (UNOESC) and Programa de Mestrado em Biociências e Saúde (PPGBS) for financial support. This work was also supported by grants from CAPES (Coordenação de Aperfeiçoamento de Pessoal e Nível Superior) by CAPES Pró-Equipamentos/2014 and FAPESC (Fundação de Amparo a Pesquisa e Inovação do Estado de Santa Catarina) by FAPESC nº 06/2017—Apoio a Grupos de Pesquisa das Instituições do Sistema ACAFE.
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Highlights
• Mn contributes to oxidative/metabolic impairment in different brain cell lines.
• Astroglial cells are more sensitive to Mn damage.
• Probucol prevent a decrease on cellular viability in neuronal and glial cells.
• Probucol prevent MRC Complex I and II inhibition and ROS production in neuronal and/or glial cells.
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da Silva, E.B., Eichwald, T., Glaser, V. et al. Protective Effects of Probucol on Different Brain Cells Exposed to Manganese. Neurotox Res 40, 276–285 (2022). https://doi.org/10.1007/s12640-021-00458-3
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DOI: https://doi.org/10.1007/s12640-021-00458-3