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Creatine and Pyruvate Prevent the Alterations Caused by Tyrosine on Parameters of Oxidative Stress and Enzyme Activities of Phosphoryltransfer Network in Cerebral Cortex of Wistar Rats

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Abstract

Tyrosine accumulates in inborn errors of tyrosine catabolism, especially in tyrosinemia type II. In this disease caused by tyrosine aminotransferase deficiency, eyes, skin, and central nervous system disturbances are found. In the present study, we investigated the chronic effect of tyrosine methyl ester (TME) and/or creatine plus pyruvate on some parameters of oxidative stress and enzyme activities of phosphoryltransfer network in cerebral cortex homogenates of 21-day-old Wistar. Chronic administration of TME induced oxidative stress and altered the activities of adenylate kinase and mitochondrial and cytosolic creatine kinase. Total sulfhydryls content, GSH content, and GPx activity were significantly diminished, while DCFH oxidation, TBARS content, and SOD activity were significantly enhanced by TME. On the other hand, TME administration decreased the activity of CK from cytosolic and mitochondrial fractions but enhanced AK activity. In contrast, TME did not affect the carbonyl content and PK activity in cerebral cortex of rats. Co-administration of creatine plus pyruvate was effective in the prevention of alterations provoked by TME administration on the oxidative stress and the enzymes of phosphoryltransfer network, except in mitochondrial CK, AK, and SOD activities. These results indicate that chronic administration of TME may stimulate oxidative stress and alter the enzymes of phosphoryltransfer network in cerebral cortex of rats. In case this also occurs in the patients affected by these disorders, it may contribute, along with other mechanisms, to the neurological dysfunction of hypertyrosinemias, and creatine and pyruvate supplementation could be beneficial to the patients.

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Acknowledgments

This work was supported in part by grants from Conselho Nacional de Desenvolvimento Científico e Tecnoloógico (CNPq-Brazil) and Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS, RS-Brazil).

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The authors declare that there is no conflict of interest disclosure associated with this manuscript.

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Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, 90.035-003, Porto Alegre, RS, Brazil

    Rodrigo Binkowski de Andrade, Tanise Gemelli, Denise Bertin Rojas, Narielle Ferner Bonorino, Bruna May Lopes Costa, Carlos Severo Dutra-Filho & Clovis Milton Duval Wannmacher

  2. Centro Universitário Metodista IPA, Rua Cel. Joaquim Pedro Salgado, 80, 90420-060, Porto Alegre, RS, Brazil

    Cláudia Funchal

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  1. Rodrigo Binkowski de Andrade
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de Andrade, R.B., Gemelli, T., Rojas, D.B. et al. Creatine and Pyruvate Prevent the Alterations Caused by Tyrosine on Parameters of Oxidative Stress and Enzyme Activities of Phosphoryltransfer Network in Cerebral Cortex of Wistar Rats. Mol Neurobiol 51, 1184–1194 (2015). https://doi.org/10.1007/s12035-014-8791-9

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