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Guanidinoacetate Decreases Antioxidant Defenses and Total Protein Sulfhydryl Content in Striatum of Rats

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Abstract

Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of guanidinoacetate (GAA) and depletion of creatine. Affected patients present epilepsy and mental retardation whose pathogeny is unclear. In the present study we investigated the in vitro and in vivo (intrastriatal administration) effects of GAA on some oxidative stress parameters in rat striatum. Sixty-day-old rats were used for intrastriatal infusion of GAA. For the in vitro studies, 60-day-old Wistar rats were killed by decapitation and the striatum was pre-incubated for 1 h at 37°C in the presence of GAA at final concentrations ranging from 10 to 100 μM. Parameters of oxidative stress such as total radical-trapping antioxidant potential (TRAP), antioxidant enzymes (SOD, GPx, and CAT), protein carbonyl and thiol contents were measured. DNA damage was also evaluated. Results showed that GAA administration (in vivo studies) or the addition of 100 μM GAA to assays (in vitro studies) significantly decreased TRAP, SOD activity, and total thiol levels in rat striatum. In contrast, this guanidino compound did not alter protein carbonyl content and the activities of CAT and GPx. DNA damage was not found after intrastriatal administration of GAA. The data indicate that the metabolite accumulating in GAMT deficiency decreases antioxidant capacity and total thiol content in the striatum. It is therefore presumed that this pathomechanism may contribute at least in part to the pathophysiology of the brain injury observed in patients affected by GAMT deficiency.

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Acknowledgments

This work was supported in part by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq—Brazil) and by the FINEP Research Grant “Rede Instituto Brasileiro de Neurociência (IBN-Net)—# 01.06.0842-00.”

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Authors and 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

    Alexandra I. Zugno, Francieli M. Stefanello, Emilene B. S. Scherer, Cristiane Mattos, Carolina D. Pederzolli, Clovis M. D. Wannmacher, Moacir Wajner, Carlos S. Dutra-Filho & Angela T. S. Wyse

  2. Laboratório de Imunologia e Mutagênese, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil

    Vanessa M. Andrade

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  1. Alexandra I. Zugno
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  10. Angela T. S. Wyse
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Correspondence to Angela T. S. Wyse.

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Zugno, A.I., Stefanello, F.M., Scherer, E.B.S. et al. Guanidinoacetate Decreases Antioxidant Defenses and Total Protein Sulfhydryl Content in Striatum of Rats. Neurochem Res 33, 1804–1810 (2008). https://doi.org/10.1007/s11064-008-9636-6

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