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Intracerebroventricular administration of N-acetylaspartic acid impairs antioxidant defenses and promotes protein oxidation in cerebral cortex of rats

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Abstract

N-acetylaspartic acid (NAA) is the biochemical hallmark of Canavan Disease, an inherited metabolic disease caused by deficiency of aspartoacylase activity. NAA is an immediate precursor for the enzyme-mediated biosynthesis of N-acetylaspartylglutamic acid (NAAG), whose concentration is also increased in urine and cerebrospinal fluid of patients affected by CD. This neurodegenerative disorder is clinically characterized by severe mental retardation, hypotonia and macrocephaly, and generalized tonic and clonic type seizures. Considering that the mechanisms of brain damage in this disease remain not fully understood, in the present study we investigated whether intracerebroventricular administration of NAA or NAAG elicits oxidative stress in cerebral cortex of 30-day-old rats. NAA significantly reduced total radical-trapping antioxidant potential, catalase and glucose 6-phosphate dehydrogenase activities, whereas protein carbonyl content and superoxide dismutase activity were significantly enhanced. Lipid peroxidation indices and glutathione peroxidase activity were not affected by NAA. In contrast, NAAG did not alter any of the oxidative stress parameters tested. Our results indicate that intracerebroventricular administration of NAA impairs antioxidant defenses and induces oxidative damage to proteins, which could be involved in the neurotoxicity of NAA accumulation in CD patients.

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Acknowledgements

This work was supported by the research grants from Programa de Núcleos de Excelência (PRONEX), CAPES, Brazilian National Research Council (CNPq), PROPESQ/UFRGS, PIC/UFCSPA 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, Porto Alegre, RS, Brasil

    Francieli Juliana Rockenbach, Fernanda Rech Zanin, Angela T. S. Wyse, Clóvis 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, Brasil

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

  3. Departamento de Ciências Fisiológicas, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brasil

    Nicoli Taiana Henn, Eline Coan Romagna & Ângela de Mattos Dutra

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  1. Carolina Didonet Pederzolli
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  11. Carlos S. Dutra-Filho
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Correspondence to Carlos S. Dutra-Filho.

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Pederzolli, C.D., Rockenbach, F.J., Zanin, F.R. et al. Intracerebroventricular administration of N-acetylaspartic acid impairs antioxidant defenses and promotes protein oxidation in cerebral cortex of rats. Metab Brain Dis 24, 283–298 (2009). https://doi.org/10.1007/s11011-009-9137-6

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