Involvement of NO in the convulsive behavior and oxidative damage induced by the intrastriatal injection of methylmalonate.
Acute intrastriatal administration of methylmalonic acid (MMA) induces convulsions through NMDA receptor-mediated mechanisms and increases production of end products of oxidative damage. Although it has been demonstrated that nitric oxide (NO) production increases with NMDA receptor stimulation and contributes to the oxidative damage observed in several neurodegenerative disorders, the role of NO in MMA-induced convulsions has not been investigated to date. In the present study we investigated the effects of the intrastriatal injection of N(omega)-nitro-L-arginine methyl ester (L-NAME: 10(-4) to 10(0) nmol/0.5 microl) on the convulsions and striatal protein carbonylation induced by the intrastriatal injection of MMA (4.5 micromol/1.5 microl). l-NAME (10(-3) to 10(-1)nmol) protected against MMA-induced convulsions and protein carbonylation ex vivo. These results suggest the involvement of NO in the convulsive behavior and protein carbonylation elicited by MMA.
Royes
Luiz Fernando Freire
LF
Laboratory of Psychopharmacology and Neurotoxicology, Department of Physiology and Pharmacology, Federal University of Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Fighera
Michele Rechia
MR
Furian
Ana Flávia
AF
Oliveira
Mauro Schneider
MS
Fiorenza
Natália Gindri
NG
de Carvalho Myskiw
Jociane
J
Frussa-Filho
Roberto
R
Mello
Carlos Fernando
CF
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008764:Methylmalonic Acid / Q000008:administration & dosage*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D008764:Methylmalonic Acid; D019331:NG-Nitroarginine Methyl Ester