Amino Acids

, Volume 44, Issue 3, pp 857–868

Acute creatine administration improves mitochondrial membrane potential and protects against pentylenetetrazol-induced seizures

  • Leonardo Magno Rambo
  • Leandro Rodrigo Ribeiro
  • Iuri Domingues Della-Pace
  • Daniel Neis Stamm
  • Rogério da Rosa Gerbatin
  • Marina Prigol
  • Simone Pinton
  • Cristina Wayne Nogueira
  • Ana Flávia Furian
  • Mauro Schneider Oliveira
  • Michele Rechia Fighera
  • Luiz Fernando Freire Royes
Original Article

DOI: 10.1007/s00726-012-1408-6

Cite this article as:
Rambo, L.M., Ribeiro, L.R., Della-Pace, I.D. et al. Amino Acids (2013) 44: 857. doi:10.1007/s00726-012-1408-6

Abstract

A growing body of evidence indicates that creatine (Cr) exerts beneficial effects on a variety of pathologies where energy metabolism and oxidative stress play an etiological role. However, the benefits of Cr treatment for epileptics are still shrouded in controversy. In the present study, we found that acute Cr treatment (300 mg/kg, p.o.) prevented the increase in electroencephalographic wave amplitude typically elicited by PTZ (30, 45 or 60 mg/kg, i.p.). Cr treatment also increased the latency periods of first myoclonic jerks, lengthened the latency periods of the generalized tonic–clonic seizures and reduced the time spent in the generalized tonic–clonic seizures induced by PTZ (60 mg/kg). Administration of PTZ (all doses) decreased Na+, K+-ATPase activity as well as adenosine triphosphate (ATP) and adenosine diphosphate levels in the cerebral cortex, but Cr treatment prevented these effects. Cr administration also prevented increases in xanthine oxidase activity, adenosine monophosphate levels, adenosine levels, inosine levels and uric acid levels that normally occur after PTZ treatment (60 mg/kg, i.p.). We also showed that Cr treatment increased the total Cr (Cr + PCr) content, creatine kinase activity and the mitochondrial membrane potential (ΔΨ) in the cerebral cortex. In addition, Cr prevented PTZ-induced mitochondrial dysfunction characterized by decreasing ΔΨ, increasing thiobarbituric acid-reactive substance levels and increasing protein carbonylation. These experimental findings reinforce the idea that mitochondrial dysfunction plays a critical role in models of epileptic seizures and suggest that buffering brain energy levels through Cr treatment may be a promising therapeutic approach for the treatment of this neurological disease.

Keywords

Creatine Pentylenetetrazol Na+, K+-ATPase Mitochondrial membrane potential Purine catabolism 

Copyright information

© Springer-Verlag Wien 2012

Authors and Affiliations

  • Leonardo Magno Rambo
    • 1
    • 2
  • Leandro Rodrigo Ribeiro
    • 1
    • 2
  • Iuri Domingues Della-Pace
    • 2
    • 3
  • Daniel Neis Stamm
    • 2
  • Rogério da Rosa Gerbatin
    • 2
  • Marina Prigol
    • 1
  • Simone Pinton
    • 1
  • Cristina Wayne Nogueira
    • 1
  • Ana Flávia Furian
    • 3
  • Mauro Schneider Oliveira
    • 1
    • 3
  • Michele Rechia Fighera
    • 1
    • 2
    • 3
    • 5
  • Luiz Fernando Freire Royes
    • 1
    • 2
    • 3
    • 4
  1. 1.Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e ExatasUniversidade Federal de Santa MariaSanta MariaBrazil
  2. 2.Laboratório de Bioquímica do Exercício, Centro de Educação Física e DesportosUniversidade Federal de Santa MariaSanta MariaBrazil
  3. 3.Programa de Pós-graduação em Farmacologia, Centro de Ciências da SaúdeUniversidade Federal de Santa MariaSanta MariaBrazil
  4. 4.Departamento de Métodos e Técnicas Desportivas, Centro de Educação Física e DesportosUniversidade Federal de Santa Maria (UFSM)Santa MariaBrazil
  5. 5.Departamento de Neuropsiquiatria, Centro de Ciências da SaúdeUniversidade Federal de Santa MariaSanta MariaBrazil

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