title: Phenylalanine induces oxidative stress and decreases the viability of rat astrocytes: possible relevance for the pathophysiology of neurodegeneration in phenylketonuria.
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.
authors.affiliation: 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.
authors.forename: Thales
authors.initials: T
authors.lastname: Preissler
authors.affiliation: 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.
authors.forename: Ivi Juliana
authors.initials: IJ
authors.lastname: Bristot
authors.affiliation: 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.
authors.forename: Bruna May Lopes
authors.initials: BM
authors.lastname: Costa
authors.affiliation: 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.
authors.forename: Elissa Kerli
authors.initials: EK
authors.lastname: Fernandes
authors.affiliation: 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.
authors.forename: Elenara
authors.initials: E
authors.lastname: Rieger
authors.affiliation: 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.
authors.forename: Vanessa Trindade
authors.initials: VT
authors.lastname: Bortoluzzi
authors.affiliation: 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.
authors.forename: Itiane Diehl
authors.initials: ID
authors.lastname: de Franceschi
authors.affiliation: 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.
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
authors.affiliation: 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.
authors.forename: José Claudio Fonseca
authors.initials: JC
authors.lastname: Moreira
authors.affiliation: 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. clovisdw@ufrgs.br.
authors.forename: Clovis Milton Duval
authors.initials: CM
authors.lastname: Wannmacher
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010649:Phenylalanine / Q000494:pharmacology*; D010661:Phenylketonurias / Q000378:metabolism* / Q000473:pathology; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010649:Phenylalanine; D011770:Pyruvate Kinase; D003402:Creatine Kinase; D000263:Adenylate Kinase
keywords: Astrocytes; Oxidative stress; Phenylalanine