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Neuroprotective Effect of Creatine and Pyruvate on Enzyme Activities of Phosphoryl Transfer Network and Oxidative Stress Alterations Caused by Leucine Administration in Wistar Rats

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Abstract

Maple syrup urine disease is an autosomal metabolic disease caused by a deficiency of branched-chain α-keto acid dehydrogenase complex activity. In this disease occur the accumulation of the branched-chain amino acids leucine, isoleucine, and valine and their corresponding branched-chain α-keto acids in the tissues and body fluids. The affected patients may present psychomotor development delay and mental retardation. The pathophysiology of maple syrup urine disease is not entirely understood, but leucine seems to be the primary neurotoxic metabolite. Creatine and pyruvate are energetics and antioxidants substances. In this study, we investigated the effects of leucine administration and co-administration of creatine plus pyruvate on several parameters of oxidative stress and phosphoryl transfer network in cerebral cortex and hippocampus of Wistar rats treated from the 8th to the 21st postpartum day. Leucine induced oxidative stress and diminished the activities of pyruvate kinase, adenylate kinase, cytosolic and mitochondrial creatine kinase. Co-administration of creatine plus pyruvate prevented the alterations provoked by leucine administration on the oxidative stress and the enzymes of phosphoryltransfer network. These results indicate that chronic administration of leucine may stimulate oxidative stress and alters the enzymes of phosphoryltransfer network in the cerebral cortex and hippocampus of the rats. It is possible that these effects may contribute, along with other mechanisms, to the neurological dysfunction found in patients affected by maple syrup urine disease. In this case, it is possible that creatine plus pyruvate supplementation could benefit to the patients.

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Acknowledgments

This work was supported by the research grants from, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) number 306928/2014-0, Fundação de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS).

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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, Porto Alegre, RS, 90035-003, Brazil

    Elenara Rieger, Itiane Diehl de Franceschi, Thales Preissler & Clovis Milton Duval Wannmacher

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  1. Elenara Rieger
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  2. Itiane Diehl de Franceschi
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Rieger, E., de Franceschi, I.D., Preissler, T. et al. Neuroprotective Effect of Creatine and Pyruvate on Enzyme Activities of Phosphoryl Transfer Network and Oxidative Stress Alterations Caused by Leucine Administration in Wistar Rats. Neurotox Res 32, 575–584 (2017). https://doi.org/10.1007/s12640-017-9762-5

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  • DOI: https://doi.org/10.1007/s12640-017-9762-5

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