RESUMO
The influence of creatine or its derivates on the cell energy potential may be one of the possibl approaches to induce neuroprotection. Effect of creamide (creatinylglycine ethylic ether fumarate) on the brain injury was studied in the experimental model of the brain ischemia/reperfusion in rats. The experiments were carried out in 14-20 weeks old male Wistar rats weighing 240-300 g, anesthetized by chloral hydrate (430 mg/kg). Creamide was administered intravenously at the doses of 50, 70, 140, and 280 mg/kg. For comparison phosphocreatine was used at the dose of 255 mg/kg. Creamide and phosphocreatine were administered intravenously (in volume of 1 ml within 5 min) 30 min before cerebral middle artery occlusion. Focal cerebral ischemia for 30 min was produced by endovascular suture occlusion with the subsequent 48 h reperfusion period. Creamide administration resulted in dose-dependent decrease of brain ischemic injury. Creamide administered at the doses of 140 and 280 mg/kg was more effective as compared with phosphocreatine (255 mg/kg). The data obtained open new perspectives for further research and development of new creatine-derived drugs with neuroprotective action.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Fosfocreatina/análogos & derivados , Fosfocreatina/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Encéfalo/fisiopatologia , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Infarto da Artéria Cerebral Média/fisiopatologia , Injeções Intravenosas , Masculino , Fármacos Neuroprotetores/administração & dosagem , Fosfocreatina/administração & dosagem , Ratos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia , Fatores de TempoRESUMO
The aim of the study was to investigate neuroprotective effect of creatine glycine ethylic ether fumarate (creamide). The methods involved intragastric administration of creamide in doses of 30 and 50 mg/kg twice a day for 10 days. Focal 30 minutes cerebral ischemia model by endovascular suture occlusion of the middle cerebral artery in a rat with subsequent reperfusion period for 48 hours was produced. Assessment of creamide stability in gastric juice was performed. Ischemic lesion volume accompanying focal ischemia was visualized and determined. Similar infarction patterns had been found with histological methods. Garcia scale was used for clinical study of neurological deficit in rats. Our data suggest a significant neuroprotective effect of creamide in dosage 50 mg/kg administered twice a day which decreased brain lesion volume produced by ischemic and reperfusion injury.