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Diphenyl Diselenide Prevents Cortico-cerebral Mitochondrial Dysfunction and Oxidative Stress Induced by Hypercholesterolemia in LDL Receptor Knockout Mice

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Abstract

Recent studies have indicated a causal link between high dietary cholesterol intake and brain oxidative stress. In particular, we have previously shown a positive correlation between elevated plasma cholesterol levels, cortico-cerebral oxidative stress and mitochondrial dysfunction in low density lipoprotein receptor knockout (LDLr−/−) mice, a mouse model of familial hypercholesterolemia. Here we show that the organoselenium compound diphenyl diselenide (PhSe)2 (1 mg/kg; o.g., once a day for 30 days) significantly blunted the cortico-cerebral oxidative stress and mitochondrial dysfunction induced by a hypercholesterolemic diet in LDLr−/− mice. (PhSe)2 effectively prevented the inhibition of complex I and II activities, significantly increased the reduced glutathione (GSH) content and reduced lipoperoxidation in the cerebral cortex of hypercholesterolemic LDLr−/− mice. Overall, (PhSe)2 may be a promising molecule to protect against hypercholesterolemia-induced effects on the central nervous system, in addition to its already demonstrated antiatherogenic effects.

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Acknowledgments

This work was supported by grants from the Brazilian institutions Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and the Fundação de Apoio à Pesquisa do Estado de Santa Catarina (FAPESC).

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Authors and Affiliations

  1. Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC, 88040-900, Brazil

    Jade de Oliveira, Eduardo Luiz Gasnhar Moreira, Gianni Mancini, Mariana Appel Hort, Alexandra Latini, Marcelo Farina & Andreza Fabro de Bem

  2. Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, 88049-900, Brazil

    Eduardo Luiz Gasnhar Moreira & Rosa Maria Ribeiro-do-Valle

  3. Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, RS, 97105900, Brazil

    João Batista Teixeira da Rocha

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  1. Jade de Oliveira
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  8. João Batista Teixeira da Rocha
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  9. Andreza Fabro de Bem
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Correspondence to Andreza Fabro de Bem.

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de Oliveira, J., Moreira, E.L.G., Mancini, G. et al. Diphenyl Diselenide Prevents Cortico-cerebral Mitochondrial Dysfunction and Oxidative Stress Induced by Hypercholesterolemia in LDL Receptor Knockout Mice. Neurochem Res 38, 2028–2036 (2013). https://doi.org/10.1007/s11064-013-1110-4

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  • DOI: https://doi.org/10.1007/s11064-013-1110-4

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