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Metabolic Brain Disease

, Volume 25, Issue 2, pp 145–154 | Cite as

Acute administration of 5-oxoproline induces oxidative damage to lipids and proteins and impairs antioxidant defenses in cerebral cortex and cerebellum of young rats

  • Carolina Didonet Pederzolli
  • Caroline Paula Mescka
  • Bernardo Remuzzi Zandoná
  • Daniella de Moura Coelho
  • Ângela Malysz Sgaravatti
  • Mirian Bonaldi Sgarbi
  • Angela Terezinha de Souza Wyse
  • Clóvis Milton Duval Wannmacher
  • Moacir Wajner
  • Carmen Regla Vargas
  • Carlos Severo Dutra-Filho
Original Paper

Abstract

5-Oxoproline accumulates in glutathione synthetase deficiency, an autossomic recessive inherited disorder clinically characterized by hemolytic anemia, metabolic acidosis, and severe neurological symptoms whose mechanisms are poorly known. In the present study we investigated the effects of acute subcutaneous administration of 5-oxoproline to verify whether oxidative stress is elicited by this metabolite in vivo in cerebral cortex and cerebellum of 14-day-old rats. Our results showed that the acute administration of 5-oxoproline is able to promote both lipid and protein oxidation, to impair brain antioxidant defenses, to alter SH/SS ratio and to enhance hydrogen peroxide content, thus promoting oxidative stress in vivo, a mechanism that may be involved in the neuropathology of gluthatione synthetase deficiency.

Keywords

5-Oxoproline Glutathione synthetase deficiency Oxidative stress Antioxidant defenses 

Notes

Acknowledgments

This work was supported by the research grants from Programa de Núcleos de Excelência (PRONEX), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and FINEP Rede Instituto Brasileiro de Neurociência (IBN-Net #01.06.0842-00).

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Carolina Didonet Pederzolli
    • 1
    • 2
  • Caroline Paula Mescka
    • 1
  • Bernardo Remuzzi Zandoná
    • 1
  • Daniella de Moura Coelho
    • 3
  • Ângela Malysz Sgaravatti
    • 1
    • 2
  • Mirian Bonaldi Sgarbi
    • 1
  • Angela Terezinha de Souza Wyse
    • 1
    • 2
  • Clóvis Milton Duval Wannmacher
    • 1
    • 2
  • Moacir Wajner
    • 1
    • 2
    • 3
  • Carmen Regla Vargas
    • 3
    • 4
  • Carlos Severo Dutra-Filho
    • 1
    • 2
  1. 1.Departamento de Bioquímica, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  3. 3.Serviço de Genética MédicaHospital de Clínicas de Porto Alegre (HCPA)Porto AlegreBrazil
  4. 4.Departamento de Análises Clínicas, Faculdade de FarmáciaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil

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