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Hum Exp Toxicol. 2014 Oct;33(10):1008-16. doi: 10.1177/0960327113520017. Epub 2014 Jan 21.

The protective effects of endothelin-A receptor antagonist BQ-123 in pentylenetetrazole-induced seizure in rats.

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Department of Physiology, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey
Department of Physiology, Faculty of Medicine, Yildirım Beyazit University, Ankara, Turkey.
Department of Biochemistry, Tokat State Hospital, Tokat, Turkey.
Department of Histology and Embryology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey.


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.


BQ-123; Pentylenetetrazole; endothelin receptor antagonist; seizure

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