Methylene blue prevents methylmalonate-induced seizures and oxidative damage in rat striatum.
Methylene blue (MB) is a thiazine dye with cationic and lipophilic properties that acts as an electron transfer mediator in the mitochondria. Due to this metabolic improving activity and free radicals scavenging effects, MB has been used in the treatment of methemoglobinemia and ifosfamide-induced encephalopathy. Considering that methylmalonic acidemia consists of a group of inherited metabolic disorders biochemically characterized by impaired mitochondrial oxidative metabolism and reactive species production, we decided to investigate whether MB, protects against the behavioral and neurochemical alterations elicited by the intrastriatal injection of methylmalonate (MMA). In the present study we showed that intrastriatal injection of MB (0.015-1.5nmol/0.5microl) protected against seizures (evidenced by electrographic recording), protein carbonylation and Na(+),K(+)-ATPase inhibition ex vivo induced by MMA (4.5micromol/1.5microl). Furthermore, we investigated whether convulsions elicited by intrastriatal MMA administration are accompanied by striatal protein carbonyl content increase and changes in Na(+),K(+)-ATPase activity in rat striatum. The effect of MB (0.015-1.5nmol/0.5microl) and MMA (4.5micromol/0.5microl) on striatal NO(x) (NO(2) plus NO(3)) content was also evaluated. Statistical analysis revealed that the MMA-induced NO(x) content increase was attenuated by intrastriatal injection of MB and the duration of convulsive episodes correlated with Na(+),K(+)-ATPase inhibition, but not with MMA-induced total protein carbonylation. In view of that MB decreases MMA-induced neurotoxicity assessed by behavioral and neurochemical parameters, the authors suggest that MB may be of value to attenuate neurological deficits of methylmalonic acidemic patients.
Furian
Ana Flávia
AF
Laboratorio de Neurotoxicidade e Psicofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Fighera
Michele Rechia
MR
Oliveira
Mauro Schneider
MS
Ferreira
Ana Paula de Oliveira
AP
Fiorenza
Natália Gindri
NG
de Carvalho Myskiw
Jociane
J
Petry
João Carlos
JC
Coelho
Rafael Correa
RC
Mello
Carlos Fernando
CF
Royes
Luiz Fernando Freire
LF
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004569:Electroencephalography; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D008764:Methylmalonic Acid / Q000633:toxicity*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D008764:Methylmalonic Acid; D000254:Sodium-Potassium-Exchanging ATPase; D008751:Methylene Blue