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Phenylalanine induces oxidative stress and decreases the viability of rat astrocytes: possible relevance for the pathophysiology of neurodegeneration in phenylketonuria

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Abstract

The aim of this study was to investigate the effects of phenylalanine on oxidative stress and some metabolic parameters in astrocyte cultures from newborn Wistar rats. Astrocytes were cultured under four conditions: control (0.4 mM phenylalanine concentration in the Dulbecco’s Modified Eagle Medium (DMEM) solution), Phe addition to achieve 0.5, 1.0 or 1.5 mM final phenylalanine concentrations. After 72 h the astrocytes were separated for the biochemical measurements. Overall measure of mitochondrial function by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell viability measured by lactate dehydrogenase (LDH) assays indicated that phenylalanine induced cell damage at the three concentrations tested. The alteration on the various parameters of oxidative stress indicated that phenylalanine was able to induce free radicals production. Therefore, our results strongly suggest that Phe at concentrations usually found in PKU induces oxidative stress and consequently cell death in astrocytes cultures. Considering the importance of the astrocytes for brain function, it is possible that these astrocytes alterations may contribute to the brain damage found in PKU patients.

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Acknowledgments

This work was supported by the research grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

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Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, CEP, Porto Alegre, RS, 90035-003, Brazil

    Thales Preissler, Ivi Juliana Bristot, Bruna May Lopes Costa, Elissa Kerli Fernandes, Elenara Rieger, Vanessa Trindade Bortoluzzi, Itiane Diehl de Franceschi, Carlos Severo Dutra-Filho, José Claudio Fonseca Moreira & Clovis Milton Duval Wannmacher

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  1. Thales Preissler
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  2. Ivi Juliana Bristot
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Correspondence to Clovis Milton Duval Wannmacher.

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Preissler, T., Bristot, I.J., Costa, B.M.L. et al. Phenylalanine induces oxidative stress and decreases the viability of rat astrocytes: possible relevance for the pathophysiology of neurodegeneration in phenylketonuria. Metab Brain Dis 31, 529–537 (2016). https://doi.org/10.1007/s11011-015-9763-0

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