Levosimendan exerts anticonvulsant properties against PTZ-induced seizures in mice through activation of nNOS/NO pathway: Role for K-ATP channel

Gooshe, M. and Tabaeizadeh, M. and Aleyasin, A.R. and Mojahedi, P. and Ghasemi, K. and Yousefi, F. and Vafaei, A. and Amini-Khoei, H. and Amiri, S. and Dehpour, A.R. (2017) Levosimendan exerts anticonvulsant properties against PTZ-induced seizures in mice through activation of nNOS/NO pathway: Role for K-ATP channel. LIFE SCIENCES, 168. pp. 38-46.

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Abstract

Aims: Although approving new anticonvulsants was a major breakthrough in the field of epilepsy control, so far we have met limited success in almost one third of patients suffering from epilepsy and a definite and reliable method is yet to be found. Levosimendan demonstrated neuroprotective effects and reduced mortality in conditions in which seizure can be an etiology of death; however, the underlying neuroprotective mechanisms of levosimendan still eludes us. In the light of evidence suggesting levosimendan can be a K-ATP channel opener and nitrergic pathway activator, levosimendan may exert antiseizure effects through K-ATP channels and nitrergic pathway. Main methods: In this study, the effects of levosimendan on seizure susceptibility was studied by PTZ-induced seizures model in mice. Key findings: Administration of a single effective dose of levosimendan significantly increased seizures threshold and the nitrite level in the hippocampus and temporal cortex. Pretreatment with noneffective doses of glibenclamide (a K-ATP channel blocicer) and L-NAME (a non-selective NOS inhibitor) neutralize the anticonvulsant and nitrite elevating effects of levosimendan. While 7-NI (a neural NOS inhibitor) blocked the anticonvulsant effect of levosimendan, Aminoguanidine (an inducible NOS inhibitor) failed to affect the anticonvulsant effects of levosimendan. Cromakalim (a K-ATP, channel opener) or L-arginine (an NO precursor) augmented the anticonvulsant effects of a subeffective dose of levosimendan. Moreover, co-administration of noneffective doses of Glibenclamide and L-NAME demonstrated a synergistic effect in blocking the anticonvulsant effects of levosimendan. Significance: Levosimendan has anticonvulsant effects possibly via K-ATP/nNOS/NO pathway activation in the hippocampus and temporal cortex. (C) 2016 Elsevier Inc. All rights reserved.

Item Type: Article
Uncontrolled Keywords: Seizure; Levosimendan; PTZ; K-ATP channels; Nitrergic system
Subjects: WH Hemic and Lymphatic System
WL Nervous system
Divisions: Faculty of Medicine > Basic Sciences Academic Groups > Department of Physiology
Depositing User: zahra bagheri .
Date Deposited: 28 Jun 2017 08:15
Last Modified: 03 Jul 2017 09:39
URI: http://eprints.skums.ac.ir/id/eprint/570

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