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

• Published in: Metabolic brain disease Vol. 31; no. 3; pp. 529 - 537
• Main Authors: Preissler, Thales, Bristot, Ivi Juliana, Costa, Bruna May Lopes, Fernandes, Elissa Kerli, Rieger, Elenara, Bortoluzzi, Vanessa Trindade, de Franceschi, Itiane Diehl, Dutra-Filho, Carlos Severo, Moreira, José Claudio Fonseca, Wannmacher, Clovis Milton Duval
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-06-2016; Springer Nature B.V
• Subjects: Adenylate Kinase - metabolism; Animals; Astrocytes - drug effects; Astrocytes - metabolism; Astrocytes - pathology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Survival - drug effects; Cells, Cultured; Creatine Kinase - metabolism; Metabolic Diseases; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Nerve Degeneration - metabolism; Nerve Degeneration - pathology; Neurology; Neurosciences; Oncology; Original Article; Oxidative Stress - drug effects; Phenylalanine - pharmacology; Phenylketonurias - metabolism; Phenylketonurias - pathology; Pyruvate Kinase - metabolism; Rats; Rats, Wistar; Phenylalanine; Oxidative stress; Astrocytes
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-015-9763-0

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.