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In vivo neuroprotective effect of L-carnitine against oxidative stress in maple syrup urine disease

Metabolic Brain Disease volume 26, pages 21–28 (2011)Cite this article

Abstract

Maple syrup urine disease (MSUD) is an autosomal recessive inborn error of metabolism caused by deficiency of the activity of the mitochondrial enzyme complex branched-chain α-keto acid dehydrogenase (BCKAD) leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine and their corresponding branched-chain α-keto acids. Affected patients present severe brain dysfunction manifested such as ataxia, seizures, coma, psychomotor delay and mental retardation. The mechanisms of brain damage in this disease remain poorly understood. Recent studies have shown that oxidative stress may be involved in neuropathology of MSUD. L-Carnitine (L-Car) is considered a potential antioxidant through its action against peroxidation as a scavenger of reactive oxygen species and by its stabilizing effect of damage to cell membranes. In this study we evaluate the possible neuroprotective in vivo effects of L-Car against pro-oxidative effects of BCAA in cerebral cortex of rats. L-Car prevented lipoperoxidation, measured by thiobarbituric acid-reactive substances, protein damage, measured by sulfhydryl and protein carbonyl content and alteration on catalase and glutathione peroxidase activity in rat cortex from a chemically-induced model of MSUD. Our data clearly show that L-Car may be an efficient antioxidant, protecting against the oxidative stress promoted by BCAA. If the present results are confirmed in MSUD patients, this could represent an additional therapeutic approach to the patients affected by this disease.

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Acknowledgements

This work was supported by the research grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Programa de Núcleos de Excelência (PRONEX), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), 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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The authors declare that they have no conflict of interest.

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Affiliations

  1. Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - Anexo, CEP 90035–003, Porto Alegre, RS, Brazil

    Bruna Piccoli, Carlos Jacques, Giovana Dalazen, Juliana Coelho, Marcelo Cortes, Melaine Terra & Carlos S. Dutra-Filho

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

    Tarsila Moraes, Andrea Rosa, Priscila Mazzola, Carmen Regla Vargas & Carlos S. Dutra-Filho

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

    Caroline Mescka & Carmen Regla Vargas

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  1. Caroline Mescka
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  2. Tarsila Moraes
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  12. Carlos S. Dutra-Filho
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Correspondence to Carlos S. Dutra-Filho.

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Mescka, C., Moraes, T., Rosa, A. et al. In vivo neuroprotective effect of L-carnitine against oxidative stress in maple syrup urine disease. Metab Brain Dis 26, 21–28 (2011). https://doi.org/10.1007/s11011-011-9238-x

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  • DOI: https://doi.org/10.1007/s11011-011-9238-x

Keywords

  • Maple syrup urine disease
  • L-carnitine
  • Branched-chain amino acids
  • Oxidative stress
  • Neuroprotection
  • Antioxidant