Propionic acid induces convulsions and protein carbonylation in rats

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Flávia Karine Rigo1, Liana Pasquetti, Carlos Ricardo Maneck Malfatti

  • 1Laboratório de Neurotoxicologia e Psicofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.

Neuroscience Letters
|September 26, 2006
PubMed

Insights

Propionic acid (PA) causes seizures and oxidative damage in rats, suggesting a link to NMDA receptor mechanisms. This finding may explain neurological issues seen in propionic acidemia patients.

Area of Science:

  • Neuroscience
  • Metabolic Disorders
  • Biochemistry

Background:

  • Propionic acid (PA) accumulates in patients with propionic acidemia, a metabolic disorder linked to neurological dysfunction like seizures.
  • The direct effect of PA on seizure induction in experimental models remains unclear.

Purpose of the Study:

  • To investigate if intrastriatal PA injection induces seizures in adult rats.
  • To determine if PA alters protein carbonyl content, an indicator of oxidative damage, in the rat striatum.
  • To explore the role of NMDA receptors in PA-induced neurological effects.

Main Methods:

  • Adult rats received intrastriatal injections of varying doses of propionic acid (0.6-6 micromol).
  • Seizure activity and protein carbonyl content in the striatum were measured.
  • The effect of MK-801, an NMDA receptor antagonist, on PA-induced seizures and oxidative damage was assessed.

Main Results:

  • Intrastriatal PA injection triggered seizures in rats.
  • PA administration led to increased protein carbonyl content in both injected and non-injected striata.
  • MK-801 administration prevented PA-induced seizures and protein carbonylation.

Conclusions:

  • Propionic acid induces seizures and oxidative damage in the rat striatum.
  • These effects appear to be mediated through NMDA receptor activation.
  • The findings suggest a potential role for NMDA receptors in the neurological complications of propionic acidemia.

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