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Hum Exp Toxicol ; 33(10): 1008-16, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24449761

RESUMO

Endothelin-1 has been shown to increase neuronal activity and glutaminergic synaptic transmission by endothelin-A receptors (ETAR) in the nucleus tractus solitarius neurons that play an important role in epileptic seizures. Therefore, BQ-123 as an ETAR antagonist might attenuate neuronal excitability and glutaminergic synaptic transmission. The main purpose of the present study is to investigate the protective effect of acute BQ-123 treatment against pentylenetetrazole (PTZ)-induced tonic-clonic seizures. Wistar albino rats were divided into three groups: control, PTZ, and PTZ + BQ-123 groups. BQ-123 (3 mg/kg, intravenously) was administered for 15 min before injecting with PTZ (50 mg/kg, intraperitoneally). We determined a delay resulting from BQ-123 in "duration of the seizure onset." "Number of rats with major seizure" also decreased according to scoring with video camera in PTZ + BQ-123 group. In BQ-123-treated group, there were eight rats without a major seizure, but only one rat had a delayed major seizure. The brain tissue glutathione peroxidase activity was significantly decreased in the PTZ and PTZ + BQ-123 groups. According to the results of the control group, there was a significant increase in the protein carbonyl levels of the PTZ group and a significant increase in the nitric oxide levels of the PTZ + BQ-123 group. Histological examination showed an increase in the number of neuronal hyperchromatic nucleus especially in hippocampal gyrus dentatus region of BQ-123-treated group. We concluded that BQ-123 impeded the formation and spread of seizure to a great degree. The beneficial effects of BQ-123 were comparatively supported with biochemical parameters and histological examinations.


Assuntos
Anticonvulsivantes/farmacologia , Encéfalo/efeitos dos fármacos , Antagonistas do Receptor de Endotelina A/farmacologia , Epilepsia Tônico-Clônica/prevenção & controle , Pentilenotetrazol , Peptídeos Cíclicos/farmacologia , Receptor de Endotelina A/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Epilepsia Tônico-Clônica/induzido quimicamente , Epilepsia Tônico-Clônica/metabolismo , Epilepsia Tônico-Clônica/patologia , Glutationa Peroxidase/metabolismo , Masculino , Óxido Nítrico/metabolismo , Carbonilação Proteica , Ratos Wistar , Receptor de Endotelina A/metabolismo , Fatores de Tempo , Gravação em Vídeo
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