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Pipecolic acid induces oxidative stress in vitro in cerebral cortex of young rats and the protective role of lipoic acid

Metabolic Brain Disease volume 29, pages 175–183 (2014)Cite this article

Abstract

Pipecolic acid (PA) levels are increased in severe metabolic disorders of the central nervous system such as Zellweger syndrome, infantile Refsum disease, neonatal adrenoleukodystrophy and hyperlysinemia. The affected individuals present progressive neurological dysfunction, hypotonia and growth retardation. The mechanisms of brain damage of these disorders remain poorly understood. Since PA catabolism can produce H2O2 by oxidases, oxidative stress may be a possible mechanism involved in the pathophysiology of these diseases. Lipoic acid (LA) is considered an efficient antioxidant and has been shown to prevent oxidative stress in experimental models of many disorders of the neurologic system. Considering that to our knowledge no study investigated the role of PA on oxidative stress, in the present work we investigated the in vitro effects of PA on some oxidative stress parameters and evaluated the LA efficacy against possible pro-oxidant effects of PA in cerebral cortex of 14-day-old rats. The activities of catalase (CAT), glutathione peroxidase (GPx), glucose 6-phosphate dehydrogenase (G6PD), and glutathione S-transferase (GST) along with reduced glutathione (GSH) content were significantly decreased, while superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBA-RS) were significantly enhanced by PA. LA was able to prevent these effects by improving the activity of antioxidant enzymes, increasing GSH content and reducing TBA-RS. In contrast, glutathione reductase and 6-phosphogluconate dehydrogenase activities and sulfhydryl content were not affected. Taken together, it may be presumed that PA in vitro elicits oxidative stress and LA is able to prevent these effects.

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Acknowledgments

This study was supported by the research grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and PROPESQ/UFRGS.

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The authors declare that they have no conflict 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 Diaz Jacques, Raylane Freitas & 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

    Giovana Reche Dalazen, Melaine Terra, Juliana G. Coelho, Priscila Nicolao Mazzola & Carlos Severo Dutra-Filho

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  1. Giovana Reche Dalazen
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  2. Melaine Terra
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  3. Carlos Eduardo Diaz Jacques
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  4. Juliana G. Coelho
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  6. Priscila Nicolao Mazzola
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  7. Carlos Severo Dutra-Filho
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Correspondence to Carlos Severo Dutra-Filho.

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Dalazen, G.R., Terra, M., Jacques, C.E.D. et al. Pipecolic acid induces oxidative stress in vitro in cerebral cortex of young rats and the protective role of lipoic acid. Metab Brain Dis 29, 175–183 (2014). https://doi.org/10.1007/s11011-013-9466-3

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  • DOI: https://doi.org/10.1007/s11011-013-9466-3

Keywords

  • Pipecolic acid
  • Oxidative stress
  • Lipoic acid
  • Antioxidant
  • Rat cerebral cortex