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Pyruvate and creatine prevent oxidative stress and behavioral alterations caused by phenylalanine administration into hippocampus of rats

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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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Acknowledgements

We are grateful for the financial support of Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and FINEP Rede Instituto Brasileiro de Neurociência (IBN-Net).

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  1. Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo, 90035-003, Porto Alegre, RS, Brazil

    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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  1. Simone Luisa Berti
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Correspondence to Clóvis Milton Duval Wannmacher.

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Berti, S.L., Nasi, G.M., Garcia, C. et al. Pyruvate and creatine prevent oxidative stress and behavioral alterations caused by phenylalanine administration into hippocampus of rats. Metab Brain Dis 27, 79–89 (2012). https://doi.org/10.1007/s11011-011-9271-9

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