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N-acetylaspartic acid impairs enzymatic antioxidant defenses and enhances hydrogen peroxide concentration in rat brain

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Abstract

N-Acetylaspartic acid accumulates in Canavan Disease, a severe inherited neurometabolic disease clinically characterized by severe mental retardation, hypotonia, macrocephaly and generalized tonic and clonic type seizures. Considering that the mechanisms of brain damage in this disease remain poorly understood, in the present study we investigated the in vitro and in vivo effects of N-acetylaspartic acid on the activities of catalase, superoxide dismutase and glutathione peroxidase, as well as on hydrogen peroxide concentration in cerebral cortex of 14-day-old rats. Catalase and glutathione peroxidase activities were significantly inhibited, while hydrogen peroxide concentration was significantly enhanced by N-acetylaspartic acid both in vitro and in vivo. In contrast, superoxide dismutase activity was not altered by N-acetylaspartic acid. Our results clearly show that N-acetylaspartic acid impairs the enzymatic antioxidant defenses in rat brain. This could be involved in the pathophysiological mechanisms responsible for the brain damage observed in patients affected by Canavan Disease.

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Acknowledgements

This work was supported by the research grants from Programa de Núcleos de Excelência (PRONEX), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and FINEP Rede Instituto Brasileiro de Neurociência (IBN-Net #01.06.0842-00).

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Authors and Affiliations

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

    Caroline Paula Mescka, Alessandra Selinger Magnusson, Kátia Bueno Deckmann, Evelise de Souza Streck, Mirian Bonaldi Sgarbi, Angela T. S. Wyse, Clovis M. D. Wannmacher, Moacir Wajner & Carlos S. 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

    Carolina Didonet Pederzolli, Ângela Malysz Sgaravatti, Angela T. S. Wyse, Clovis M. D. Wannmacher, Moacir Wajner & Carlos S. Dutra-Filho

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  1. Carolina Didonet Pederzolli
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  2. Caroline Paula Mescka
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  3. Alessandra Selinger Magnusson
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  4. Kátia Bueno Deckmann
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  5. Evelise de Souza Streck
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  6. Ângela Malysz Sgaravatti
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  7. Mirian Bonaldi Sgarbi
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  8. Angela T. S. Wyse
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  9. Clovis M. D. Wannmacher
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  10. Moacir Wajner
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  11. Carlos S. Dutra-Filho
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Corresponding author

Correspondence to Carlos S. Dutra-Filho.

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Pederzolli, C.D., Mescka, C.P., Magnusson, A.S. et al. N-acetylaspartic acid impairs enzymatic antioxidant defenses and enhances hydrogen peroxide concentration in rat brain. Metab Brain Dis 25, 251–259 (2010). https://doi.org/10.1007/s11011-010-9202-1

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  • DOI: https://doi.org/10.1007/s11011-010-9202-1

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