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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.

Author information

1
Department of Physiology, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey haserdogan@yahoo.com.
2
Department of Physiology, Faculty of Medicine, Yildirım Beyazit University, Ankara, Turkey.
3
Department of Biochemistry, Tokat State Hospital, Tokat, Turkey.
4
Department of Histology and Embryology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey.

Abstract

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.

KEYWORDS:

BQ-123; Pentylenetetrazole; endothelin receptor antagonist; seizure

PMID:
24449761
DOI:
10.1177/0960327113520017
[Indexed for MEDLINE]

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