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Sodium selenite protects from 3-nitropropionic acid-induced oxidative stress in cultured primary cortical neurons

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Abstract

Selenium (Se) is an essential trace element for humans; its intake is needed to allow the proper synthesis of 25 different selenoproteins that are necessary to the normal functioning of several organs, including the brain. Accordingly, decreased Se levels have been associated with neurological disorders. In the present study, we investigated the potential beneficial effects of Se, as sodium selenite, against 3-nitropropionic acid (3-NP)-induced oxidative stress in primary cultures of mouse cortical neurons. 3-NP treatment caused a significant decrease in cellular viability, which was accompanied by decreases in mitochondrial complex II activity and reduced glutathione (GSH) content, as well as increases in reactive oxygen species (ROS) generation and oxidized glutathione (GSSG) levels. Sodium selenite pretreatment (6 days) attenuated 3-NP-induced decrease in cell viability. In addition, sodium selenite pretreatment significantly protected against 3-NP-induced increase in ROS generation and decrease in GSH/GSSG ratio. Of note, sodium selenite pretreatment did not change 3-NP-induced decrease of mitochondrial complex II activity, suggesting that Se modulates secondary events resultant from 3-NP-induced mitochondrial dyshomeostasis. In addition, sodium selenite pretreatment significantly increased glutathione peroxidase (GPx) activity. Our data provide insights into the mechanism of protection by sodium selenite, which is related, at least in part, to GPx induction.

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Acknowledgements

The financial supports by (i) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), (ii) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and (iii) Fundação de Apoio à Pesquisa do Estado de Santa Catarina (FAPESC) are gratefully acknowledged. P.S.B. acknowledges the Science Without Borders Program. M.F. is a CNPq fellowship recipient.

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Correspondence to Dirleise Colle or Marcelo Farina.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All experimental protocols were approved by the local Animal Ethics Committee of Federal University of Santa Catarina, Brazil (ethical permission numbers: PP00817/CEUA/UFSC).

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Supplementary fig. 1

Representative images of cortical neurons. Representative images of non-treated cortical neurons at DIV 3 (left panels; upper panel: 20x objective and lower panel: 40x objective) and at DIV 7 (right panels; upper panel: 20x objective and lower panel: 40x objective). The images were acquired using an Olympus IX83UC microscope connected to a capture system (CellSens Dimension 1.12). DIV: day in vitro (TIF 10898 KB)

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Colle, D., Santos, D.B., de Souza, V. et al. Sodium selenite protects from 3-nitropropionic acid-induced oxidative stress in cultured primary cortical neurons. Mol Biol Rep 46, 751–762 (2019). https://doi.org/10.1007/s11033-018-4531-y

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