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Article

The Neuroprotective Effects of Histamine H3 Receptor Antagonist E177 on Pilocarpine-Induced Status Epilepticus in Rats

1
Department of Pharmacology & Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 17666, UAE
2
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 St., 30-688 Kraków, Poland
*
Author to whom correspondence should be addressed.
Academic Editors: Istvan Bak, Attila Kiss and Istvan Lekli
Molecules 2019, 24(22), 4106; https://doi.org/10.3390/molecules24224106
Received: 3 October 2019 / Revised: 5 November 2019 / Accepted: 11 November 2019 / Published: 14 November 2019
(This article belongs to the Special Issue Oxidative Stress as a Pharmacological Target for Medicinal Chemistry)
Epilepsy is a multifaceted neurological disorder which severely affects neuronal function. Some patients may experience status epilepticus (SE), a life-threatening state of ongoing seizure activity linked to cognitive dysfunction, necessitating an immediate intervention. The potential of histamine H3 receptors in several neuropsychiatric diseases including epilepsy is well recognized. In the current study, we aimed to explore the effect of H3R antagonist E177 on prevention and termination of pilocarpine (PLC)-induced SE in rats as well as evaluating the effects of E177 on the levels of oxidative stress in hippocampus tissues. The results showed that the survival rate of animals pretreated with E177 (5 and 10 mg/kg, intraperitoneal (i.p.)) was significantly increased during the first hour of observation, and animals were protected from SE incidence and showed a prolonged average of latency to the first seizure when compared with animals pretreated with PLC (400 mg/kg, i.p.). Moreover, the protective effect of E177 (10 mg/kg) on SE was partially reversed when rats were co- administered with H3R agonist R-(α)-methylhistamine (RAM) and with the H2R antagonist zolantidine (ZOL), but not with the H1R antagonist pyrilamine (PYR). Furthermore, pretreatment with E177 (5 and 10 mg/kg) significantly decreased the abnormal levels of malondialdehyde (MDA), and increased levels of glutathione (GSH) in the hippocampal tissues of the treated rats. However, E177 failed to modulate the levels of catalase (CAT), superoxide dismutase (SOD), or acetylcholine esterase activity (AChE). Our findings suggest that the newly developed H3R antagonist E177 provides neuroprotection in a preclinical PLC-induced SE in rats, highlighting the histaminergic system as a potential therapeutic target for the therapeutic management of SE. View Full-Text
Keywords: histamine H3 receptor; antagonist; pilocarpine; status epilepticus; neuroprotection; oxidative stress; rats histamine H3 receptor; antagonist; pilocarpine; status epilepticus; neuroprotection; oxidative stress; rats
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MDPI and ACS Style

Alachkar, A.; Azimullah, S.; Ojha, S.K.; Beiram, R.; Łażewska, D.; Kieć-Kononowicz, K.; Sadek, B. The Neuroprotective Effects of Histamine H3 Receptor Antagonist E177 on Pilocarpine-Induced Status Epilepticus in Rats. Molecules 2019, 24, 4106. https://doi.org/10.3390/molecules24224106

AMA Style

Alachkar A, Azimullah S, Ojha SK, Beiram R, Łażewska D, Kieć-Kononowicz K, Sadek B. The Neuroprotective Effects of Histamine H3 Receptor Antagonist E177 on Pilocarpine-Induced Status Epilepticus in Rats. Molecules. 2019; 24(22):4106. https://doi.org/10.3390/molecules24224106

Chicago/Turabian Style

Alachkar, Alaa, Sheikh Azimullah, Shreesh K. Ojha, Rami Beiram, Dorota Łażewska, Katarzyna Kieć-Kononowicz, and Bassem Sadek. 2019. "The Neuroprotective Effects of Histamine H3 Receptor Antagonist E177 on Pilocarpine-Induced Status Epilepticus in Rats" Molecules 24, no. 22: 4106. https://doi.org/10.3390/molecules24224106

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