Propionic acid induces convulsions and protein carbonylation in rats.
Propionic acid (PA) accumulates in patients with propionic acidemia, an inherited metabolic disorder caused by the deficiency of propionyl-CoA carboxylase activity that is clinically characterized by neurological dysfunction, including seizures. However, it is not known whether PA causes seizures in experimental animals. In the current study, we investigated whether intrastriatal injection of PA (0.6-6 micromol) causes seizures and alters protein carbonyl content in the striatum of adult rats. The injection of PA caused the appearance of seizures and increased protein carbonyl content in injected and noninjected striata. PA-induced seizures and increased protein carbonylation in the striatum were prevented by the injection of MK-801 (3 nmol/0.5 microL). Our results suggest that PA causes seizures and oxidative damage by NMDA receptor-mediated mechanisms. The involvement of NMDA receptors in the pathogenesis of propionic acidemia is suggested.
Rigo
Flávia Karine
FK
Laboratório de Neurotoxicologia e Psicofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Pasquetti
Liana
L
Malfatti
Carlos Ricardo Maneck
CR
Fighera
Michele Rechia
MR
Coelho
Rafael Correa
RC
Petri
Cristiane Zanardo
CZ
Mello
Carlos Fernando
CF
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004569:Electroencephalography; D011422:Propionates / Q000633:toxicity*; D050050:Protein Carbonylation; D051381:Rats; D012640:Seizures / Q000139:chemically induced*
D011422:Propionates; C029658:propionic acid