Additive anticonvulsant effects of creatine supplementation and physical exercise against pentylenetetrazol-induced seizures.
Although physical activity and creatine supplementation have been a documented beneficial effect on neurological disorders, its implications for epilepsy are still controversial. Thus, we decided to investigate the effects of 6 weeks swimming training, creatine supplementation (300 mg/kg; p.o.) or its combination seizures and neurochemical alterations induced by pentylenetetrazol (PTZ). We found that 6 weeks of physical training or creatine supplementation decreased the duration of PTZ-induced seizures in adult male Wistar rats, as measured by cortical and hippocampal electroencephalography and behavioral analysis. Importantly, the combination between physical training and creatine supplementation had additive anticonvulsant effects, since it increased the onset latency for PTZ-induced seizures and was more effective in decrease seizure duration than physical training and creatine supplementation individually. Analysis of selected parameters of oxidative stress and antioxidant defenses in the hippocampus revealed that physical training, creatine supplementation or its combination abrogated the PTZ-elicited increase in levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonylation, as well as decrease in non-protein-thiols content, catalase (CAT) and SOD activities. In addition, this protocol of physical training and creatine supplementation prevented the PTZ-induced decrease in hippocampal Na+,K+-ATPase activity. Altogether, these results suggest that protection elicited physical training and creatine supplementation of selected targets for reactive species-mediated damage decrease of neuronal excitability and consequent oxidative damage elicited by PTZ. In conclusion, the present study shows that physical training, creatine supplementation or its combination attenuated PTZ-induced seizures and oxidative damage in vivo, and provide evidence that combination between creatine supplementation and physical exercise may be a useful strategy in the treatment of convulsive disorders.
Rambo
Leonardo Magno
LM
Centro de Ciências da Saúde, Laboratório de Neurotoxicidade e Psicofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Ribeiro
Leandro Rodrigo
LR
Oliveira
Mauro Schneider
MS
Furian
Ana Flávia
AF
Lima
Frederico Diniz
FD
Souza
Mauren Assis
MA
Silva
Luiz Fernando Almeida
LF
Retamoso
Leandro Thies
LT
Corte
Cristiane Lenz Dalla
CL
Puntel
Gustavo Orione
GO
de Avila
Daiana Silva
DS
Soares
Félix Alexandre Antunes
FA
Fighera
Michele Rechia
MR
Mello
Carlos Fernando
CF
Royes
Luiz Fernando Freire
LF
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003292:Convulsants / Q000633:toxicity*; D003401:Creatine / Q000008:administration & dosage*; D008297:Male; D018384:Oxidative Stress; D010433:Pentylenetetrazole / Q000633:toxicity*; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
D000927:Anticonvulsants; D003292:Convulsants; D003401:Creatine; D010433:Pentylenetetrazole