Creatine decreases convulsions and neurochemical alterations induced by glutaric acid in rats.

Abstract

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.

• Authors: Danieli Valnes Magni, Mauro Schneider Oliveira, Ana Flávia Furian, Natália Gindri Fiorenza, Michele Rechia Fighera, Juliano Ferreira, Carlos Fernando Mello, Luiz Fernando Freire Royes
• Journal: Brain research (Brain Res) Vol. 1185 Pg. 336-45 (Dec 14 2007) ISSN: 0006-8993 [Print] Netherlands
• PMID: 17950259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Glutarates
• Sodium-Potassium-Exchanging ATPase
• glutaric acid
• Creatine

Topics

• Analysis of Variance
• Animals
• Anticonvulsants (therapeutic use)
• Behavior, Animal (drug effects)
• Brain Chemistry (drug effects)
• Creatine (therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Interactions
• Electric Stimulation (adverse effects)
• Electroencephalography (methods)
• Glutarates
• Male
• Protein Carbonylation (drug effects)
• Rats
• Rats, Wistar
• Seizures (chemically induced, drug therapy, metabolism)
• Sodium-Potassium-Exchanging ATPase (metabolism)
• Synaptosomes (drug effects, metabolism)