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Título: The thiol-modifier effects of organoselenium compounds and their cytoprotective actions in neuronal cells
Autor(es): Galant, Letícia Selinger
Rafique, Jamal
Braga, Antônio Luiz
Braga, Felipe Camargo
Saba, Sumbal
Radi, Rafael
Rocha, João Batista Teixeira da
Santi, Claudio
Monsalve, Maria
Farina, Marcelo
Bem, Andreza Fabro de
ORCID: https://orcid.org/0000-0003-1090-5244
Assunto: Stress oxidativo
Antioxidantes
Glutationa peroxidase
Compostos organo-selênio
Efeito modificador de tiol
Neurônios
Data de publicação: 13-Abr-2020
Editora: Springer
Referência: GALANT, Letícia Selinger et al. The thiol-modifier effects of organoselenium compounds and their cytoprotective actions in neuronal cells. Neurochemical Research, v. 46, p.120-130, (2021). DOI: https://doi.org/10.1007/s11064-020-03026-x.
Abstract: Most pharmacological studies concerning the beneficial effects of organoselenium compounds have focused on their ability to mimic glutathione peroxidase (GPx). However, mechanisms other than GPx-like activity might be involved on their biological effects. This study was aimed to investigate and compare the protective effects of two well known [(PhSe)2 and PhSeZnCl] and two newly developed (MRK Picolyl and MRK Ester) organoselenium compounds against oxidative challenge in cultured neuronal HT22 cells. The thiol peroxidase and oxidase activities were performed using the glutathione reductase (GR)-coupled assay. In order to evaluate protective effects of the organoselenium compounds against oxidative challenge in neuronal HT22 cells, experiments based on glutamate-induced oxytosis and SIN-1-mediated peroxynitrite generation were performed. The thiol peroxidase activities of the studied organoselenium compounds were smaller than bovine erythrocytes GPx enzyme. Besides, (PhSe)2 and PhSeZnCl showed higher thiol peroxidase and lower thiol oxidase activities compared to the new compounds. MRK Picolyl and MRK Ester, which showed lower thiol peroxidase activity, showed higher thiol oxidase activity. Both pre- or co-treatment with (PhSe)2, PhSeZnCl, MRK Picolyl and MRK Ester protected HT22 cells against glutamate-induced cytotoxicity. (PhSe)2 and MRK Picolyl significantly prevented peroxinitrite-induced dihydrorhodamine oxidation, but this effect was observed only when HT22 were pre-treated with these compounds. The treatment with (PhSe)2 increased the protein expression of antioxidant defences (Prx3, CAT and GCLC) in HT22 cells. Taking together, our results suggest that the biological effects elicited by these compounds are not directly related to their GPx-mimetic and thiol oxidase activities, but might be linked to the up-regulation of endogenous antioxidant defences trough their thiol-modifier effects.
DOI: https://doi.org/10.1007/s11064-020-03026-x
Versão da editora: https://link.springer.com/article/10.1007/s11064-020-03026-x
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