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Neonatal hyperglycemia induces oxidative stress in the rat brain: the role of pentose phosphate pathway enzymes and NADPH oxidase

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Abstract

Recently, the consequences of diabetes on the central nervous system (CNS) have received great attention. However, the mechanisms by which hyperglycemia affects the central nervous system remain poorly understood. In addition, recent studies have shown that hyperglycemia induces oxidative damage in the adult rat brain. In this regard, no study has assessed oxidative stress as a possible mechanism that affects the brain normal function in neonatal hyperglycemic rats. Thus, the present study aimed to investigate whether neonatal hyperglycemia elicits oxidative stress in the brain of neonate rats subjected to a streptozotocin-induced neonatal hyperglycemia model (5-day-old rats). The activities of glucose-6-phosphate-dehydrogenase (G6PD), 6-phosphogluconate-dehydrogenase (6-PGD), NADPH oxidase (Nox), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), the production of superoxide anion, the thiobarbituric acid-reactive substances (TBA-RS), and the protein carbonyl content were measured. Neonatal hyperglycemic rats presented increased activities of G6PD, 6PGD, and Nox, which altogether may be responsible for the enhanced production of superoxide radical anion that was observed. The enhanced antioxidant enzyme activities (SOD, CAT, and GSHPx) that were observed in neonatal hyperglycemic rats, which may be caused by a rebound effect of oxidative stress, were not able to hinder the observed lipid peroxidation (TBA-RS) and protein damage in the brain. Consequently, these results suggest that oxidative stress could represent a mechanism that explains the harmful effects of neonatal hyperglycemia on the CNS.

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Acknowledgments

This work was supported by 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 Neurociências” (IBN-Net #01.06.0842-00). Figure 5 was produced using Servier Medical Art ( www.servier.com ).

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The authors declare that they have no conflicts of interest.

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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 (Anexo), Porto Alegre, RS, 90035-003, Brazil

    Carlos Eduardo Dias Jacques, Laila Oliveira de Souza, Fernanda Bitencourt & Carlos Severo Dutra-Filho

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

    Andrea Pereira Rosa, Priscila Nicolao Mazzola, Juliana Gonzales Coelho, Caroline Paula Mescka & Carlos Severo Dutra-Filho

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  1. Andrea Pereira Rosa
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Rosa, A.P., Jacques, C.E.D., de Souza, L.O. et al. Neonatal hyperglycemia induces oxidative stress in the rat brain: the role of pentose phosphate pathway enzymes and NADPH oxidase. Mol Cell Biochem 403, 159–167 (2015). https://doi.org/10.1007/s11010-015-2346-x

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