Pyruvate and creatine prevent oxidative stress and behavioral alterations caused by phenylalanine administration into hippocampus of rats |
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Authors: | Simone Luisa Berti Guilherme Marmontel Nasi Cristina Garcia Fernanda Luz de Castro Michely Lopes Nunes Denise Bertin Rojas Tarsila Barros Moraes Carlos Severo Dutra-Filho Clóvis Milton Duval Wannmacher |
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Institution: | Departamento de Bioquímica, Programa de Pós-Gradua??o em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil. |
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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. |
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