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Evidence that oxidative stress is increased in plasma from patients with maple syrup urine disease

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Abstract

Maple syrup urine disease (MSUD) or branched-chain α-keto aciduria (BCKA) is an inherited disorder caused by a deficiency of the branched-chain α-keto acid dehydrogenase complex (BCKAD) activity. The blockage of this pathway leads to tissue accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine and their respective keto-acids. The clinical features presented by MSUD patients include ketoacidosis, convulsions, coma, psychomotor delay and mental retardation. The mechanism of brain damage in this disease is still poorly understood. However, an increase in lipid peroxidation in vitro in cerebral cortex of young rats as well as a decrease in the antioxidant defenses has been previously observed. In the present work we evaluated different oxidative stress parameters, named reactive species of thiobarbituric acid (TBARS), total antioxidant reactivity (TAR) and total antioxidant status (TAS) in plasma of MSUD patients in order to evaluate whether oxidative stress is involved in this disorder. We verified a marked increase of plasma TBARS measurements, which is indicative of increased lipid peroxidation, as well as a decrease on plasma TAR reflecting a deficient capacity to efficiently modulate the damage associated with an increased production of reactive species. In contrast, TAS was not changed indicating that the total content of antioxidants in plasma of patients affected by MSUD was not altered. These results suggest that free radical generation is elicited in MSUD and is possibly involved in the pathophysiology of the tissue damage found in this disorder.

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Acknowledgements

This work was supported by grants from Brazilian National Research Council (CNPq), FAPERGS, and FIPE/HCPA—Brazil.

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Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Alethéa G. Barschak, Angela Sitta, Marion Deon, Carlos S. Dutra-Filho, Moacir Wajner & Carmen R. Vargas

  2. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350 CEP 90.035–903, Porto Alegre, RS, Brazil

    Alethéa G. Barschak, Angela Sitta, Marion Deon, Marcella H. de Oliveira, Moacir Wajner & Carmen R. Vargas

  3. Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Alexsandro Haeser & Carmen R. Vargas

  4. Departamento de Análises, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Carmen R. Vargas

Authors
  1. Alethéa G. Barschak
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  2. Angela Sitta
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  3. Marion Deon
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  4. Marcella H. de Oliveira
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  5. Alexsandro Haeser
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  6. Carlos S. Dutra-Filho
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  7. Moacir Wajner
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  8. Carmen R. Vargas
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Correspondence to Carmen R. Vargas.

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Barschak, A.G., Sitta, A., Deon, M. et al. Evidence that oxidative stress is increased in plasma from patients with maple syrup urine disease. Metab Brain Dis 21, 279–286 (2006). https://doi.org/10.1007/s11011-006-9030-5

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  • DOI: https://doi.org/10.1007/s11011-006-9030-5

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