title: Pyruvate and creatine prevent oxidative stress and behavioral alterations caused by phenylalanine administration into hippocampus of rats.
abstract: Phenylketonuria is characterized by a variable degree of mental retardation and other neurological features whose mechanisms are not fully understood. In the present study we investigated the effect of intrahippocampal administration of phenylalanine, isolated or associated with pyruvate or creatine, on rat behavior and on oxidative stress. Sixty-day-old male Wistar rats were randomly divided into 6 groups: saline; phenylalanine; pyruvate; creatine; phenylalanine + pyruvate; phenylalanine + creatine. Phenylalanine was administered bilaterally in the hippocampus one hour before training; pyruvate, at the same doses, was administered in the hippocampus one hour before phenylalanine; creatine was administered intraperitoneally twice a day for 5 days before training; controls received saline solution at same volumes than the other substances. Parameters of exploratory behavior and of emotionality were assessed in both training and test sessions in the open field task. Rats receiving phenylalanine did not habituate to the open field along the sessions, indicating deficit of learning/memory, but parameters of emotionality were normal, not interfering in the habituation process. Pyruvate or creatine administration prevented the lack of habituation caused by phenylalanine. Pyruvate and creatine also prevented alterations provoked by phenylalanine on lipid peroxidation, total content of sulfhydryls, total radical-trapping antioxidant potential and total antioxidant reactivity. The results suggest that the behavioral alterations provoked by intra-hippocampal administration of phenylalanine may be caused, at least in part, by oxidative stress and/or energy deficit. If this also occurs in PKU, it is possible that pyruvate and creatine supplementation to the phenylalanine-restricted diet might be beneficial to phenylketonuric patients.
authors.affiliation: Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Simone Luisa
authors.initials: SL
authors.lastname: Berti
authors.forename: Guilherme Marmontel
authors.initials: GM
authors.lastname: Nasi
authors.forename: Cristina
authors.initials: C
authors.lastname: Garcia
authors.forename: Fernanda Luz de
authors.initials: FL
authors.lastname: Castro
authors.forename: Michely Lopes
authors.initials: ML
authors.lastname: Nunes
authors.forename: Denise Bertin
authors.initials: DB
authors.lastname: Rojas
authors.forename: Tarsila Barros
authors.initials: TB
authors.lastname: Moraes
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
authors.forename: Clóvis Milton Duval
authors.initials: CM
authors.lastname: Wannmacher
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003401:Creatine / Q000008:administration & dosage*; D004734:Energy Metabolism / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010649:Phenylalanine / Q000008:administration & dosage / Q000009:adverse effects*; D010661:Phenylketonurias / Q000378:metabolism* / Q000473:pathology; D019289:Pyruvic Acid / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D010649:Phenylalanine; D019289:Pyruvic Acid; D003401:Creatine
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