Creatine decreases convulsions and neurochemical alterations induced by glutaric acid in rats.
Glutaric acidemia type I (GA-I) is an inherited metabolic disease characterized by striatal degeneration, seizures, and accumulation of glutaric acid (GA). Considering that GA impairs energy metabolism and induces reactive species generation, we investigated whether the acute administration of creatine, an amino acid with antioxidant and ergogenic properties, protects against the seizures and neurochemical alterations (inhibition of Na(+),K(+)-ATPase and increased protein carbonylation) induced by the intrastriatal injection of GA (4 micromol/striatum). We also investigated whether creatine protected against the GA-induced inhibition of glutamate uptake in vitro. Creatine administration (300 mg/kg, p.o.) decreased seizures (evidenced by electrographic changes), protein carbonylation and Na(+),K(+)-ATPase inhibition induced by GA. However, creatine, at a dose capable of fully preventing GA-induced protein carbonylation (50 and 150 mg/kg, p.o.), did not prevent convulsions and Na(+),K(+)-ATPase inhibition, suggesting that the anticonvulsant activity of creatine in this experimental model is not related to its antioxidant action. Creatine also protected against the GA-induced inhibition of l-[(3)H]glutamate uptake in synaptosomes, suggesting that creatine may reduce the deleterious effects of GA by maintaining glutamate uptake in the synaptic cleft. Therefore, considering that creatine significantly attenuates the deleterious effects of GA assessed by behavioral and neurochemical measures, it is plausible to propose the use of this amino acid as an adjuvant therapy in the management of glutaric acidemia.
Magni
Danieli Valnes
DV
Centro de Ciências da Saúde, Laboratório de Psicofarmacologia e Neurotoxicidade, Departamento de Fisiologia, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil.
Oliveira
Mauro Schneider
MS
Furian
Ana Flávia
AF
Fiorenza
Natália Gindri
NG
Fighera
Michele Rechia
MR
Ferreira
Juliano
J
Mello
Carlos Fernando
CF
Royes
Luiz Fernando Freire
LF
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D003401:Creatine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography / Q000379:methods; D005977:Glutarates; D008297:Male; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000927:Anticonvulsants; D005977:Glutarates; D000254:Sodium-Potassium-Exchanging ATPase; C035736:glutaric acid; D003401:Creatine