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Role of Catalase and Superoxide Dismutase Activities on Oxidative Stress in the Brain of a Phenylketonuria Animal Model and the Effect of Lipoic Acid

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Abstract

Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficiency of phenylalanine hydroxylase which leads to accumulation of phenylalanine and its metabolites in tissues of patients with severe neurological involvement. Recently, many studies in animal models or patients have reported the role of oxidative stress in PKU. In the present work we studied the effect of lipoic acid against oxidative stress in rat brain provoked by an animal model of hyperphenylalaninemia (HPA), induced by repetitive injections of phenylalanine and α-methylphenylalanine (a phenylalanine hydroxylase inhibitor) for 7 days, on some oxidative stress parameters. Lipoic acid prevented alterations on catalase (CAT) and superoxide dismutase (SOD), and the oxidative damage of lipids, proteins, and DNA observed in HPA rats. In addition, lipoic acid diminished reactive species generation compared to HPA group which was positively correlated to SOD/CAT ratio. We also observed that in vitro Phe inhibited CAT activity while phenyllactic and phenylacetic acids stimulated superoxide dismutase activity. These results demonstrate the efficacy of lipoic acid to prevent oxidative stress induced by HPA model in rats. The possible benefits of lipoic acid administration to PKU patients should be considered.

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Acknowledgments

This work was supported by the research grants from Brazilian National Research Council (CNPq), Programa de Núcleos de Excelência (PRONEX), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), PROPESQ/UFRGS, and FINEP/Rede Instituto Brasileiro de Neurociência (IBN-Net) #01.06.0842-00.

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

    Carlos Eduardo Diaz Jacques & Carlos Severo Dutra-Filho

  2. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Tarsila Barros Moraes, Andrea Pereira Rosa, Giovana Reche Dalazen, Melaine Terra, Juliana Gonzalez Coelho & Carlos Severo Dutra-Filho

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  1. Tarsila Barros Moraes
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  2. Carlos Eduardo Diaz Jacques
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Correspondence to Carlos Severo Dutra-Filho.

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Moraes, T.B., Jacques, C.E.D., Rosa, A.P. et al. Role of Catalase and Superoxide Dismutase Activities on Oxidative Stress in the Brain of a Phenylketonuria Animal Model and the Effect of Lipoic Acid. Cell Mol Neurobiol 33, 253–260 (2013). https://doi.org/10.1007/s10571-012-9892-5

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