The protective effects of endothelin-A receptor antagonist BQ-123 in pentylenetetrazole-induced seizure in rats.
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.
Department of Physiology, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey haserdogan@yahoo.com.
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Erdogan
Department of Physiology, Faculty of Medicine, Yildirım Beyazit University, Ankara, Turkey.
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Ekici
Department of Biochemistry, Tokat State Hospital, Tokat, Turkey.
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Katar
Department of Histology and Embryology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey.
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Kesici
Department of Histology and Embryology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey.
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Aslan
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists / Q000494:pharmacology*; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010433:Pentylenetetrazole; D010456:Peptides, Cyclic / Q000494:pharmacology*; D050050:Protein Carbonylation; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014741:Video Recording
D000927:Anticonvulsants; D065130:Endothelin A Receptor Antagonists; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D009569:Nitric Oxide; D005979:Glutathione Peroxidase; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D010433:Pentylenetetrazole
BQ-123; Pentylenetetrazole; endothelin receptor antagonist; seizure