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Article

Antagonism of Histamine H3 receptors Alleviates Pentylenetetrazole-Induced Kindling and Associated Memory Deficits by Mitigating Oxidative Stress, Central Neurotransmitters, and c-Fos Protein Expression in Rats

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Department of Pharmacology & Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 17666, UAE
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Department of Biology, College of Science, United Arab Emirates University, Al Ain 17666, UAE
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Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 17666, UAE
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Jagiellonian University Medical College, Faculty of Pharmacy, Department of Technology and Biotechnology of Drugs, Medyczna 9 St., 30-688 Kraków, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Tomasz Plech
Molecules 2020, 25(7), 1575; https://doi.org/10.3390/molecules25071575
Received: 13 March 2020 / Revised: 26 March 2020 / Accepted: 27 March 2020 / Published: 30 March 2020
Histamine H3 receptors (H3Rs) are involved in several neuropsychiatric diseases including epilepsy. Therefore, the effects of H3R antagonist E177 (5 and 10 mg/kg, intraperitoneal (i.p.)) were evaluated on the course of kindling development, kindling-induced memory deficit, oxidative stress levels (glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)), various brain neurotransmitters (histamine (HA), acetylcholine (ACh), γ-aminobutyric acid (GABA)), and glutamate (GLU), acetylcholine esterase (AChE) activity, and c-Fos protein expression in pentylenetetrazole (PTZ, 40 mg/kg) kindled rats. E177 (5 and 10 mg/kg, i.p.) significantly decreased seizure score, increased step-through latency (STL) time in inhibitory avoidance paradigm, and decreased transfer latency time (TLT) in elevated plus maze (all P < 0.05). Moreover, E177 mitigated oxidative stress by significantly increasing GSH, CAT, and SOD, and decreasing the abnormal level of MDA (all P < 0.05). Furthermore, E177 attenuated elevated levels of hippocampal AChE, GLU, and c-Fos protein expression, whereas the decreased hippocampal levels of HA and ACh were modulated in PTZ-kindled animals (all P < 0.05). The findings suggest the potential of H3R antagonist E177 as adjuvant to antiepileptic drugs with an added advantage of preventing cognitive impairment, highlighting the H3Rs as a potential target for the therapeutic management of epilepsy with accompanied memory deficits. View Full-Text
Keywords: histamine H3 receptor; antagonist; PTZ-kindling; memory impairment; neuroprotection; oxidative stress; AChE activity; c-Fos protein expression; rats histamine H3 receptor; antagonist; PTZ-kindling; memory impairment; neuroprotection; oxidative stress; AChE activity; c-Fos protein expression; rats
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MDPI and ACS Style

Alachkar, A.; Azimullah, S.; Lotfy, M.; Adeghate, E.; Ojha, S.K.; Beiram, R.; Łażewska, D.; Kieć-Kononowicz, K.; Sadek, B. Antagonism of Histamine H3 receptors Alleviates Pentylenetetrazole-Induced Kindling and Associated Memory Deficits by Mitigating Oxidative Stress, Central Neurotransmitters, and c-Fos Protein Expression in Rats. Molecules 2020, 25, 1575. https://doi.org/10.3390/molecules25071575

AMA Style

Alachkar A, Azimullah S, Lotfy M, Adeghate E, Ojha SK, Beiram R, Łażewska D, Kieć-Kononowicz K, Sadek B. Antagonism of Histamine H3 receptors Alleviates Pentylenetetrazole-Induced Kindling and Associated Memory Deficits by Mitigating Oxidative Stress, Central Neurotransmitters, and c-Fos Protein Expression in Rats. Molecules. 2020; 25(7):1575. https://doi.org/10.3390/molecules25071575

Chicago/Turabian Style

Alachkar, Alaa, Sheikh Azimullah, Mohamed Lotfy, Ernest Adeghate, Shreesh K. Ojha, Rami Beiram, Dorota Łażewska, Katarzyna Kieć-Kononowicz, and Bassem Sadek. 2020. "Antagonism of Histamine H3 receptors Alleviates Pentylenetetrazole-Induced Kindling and Associated Memory Deficits by Mitigating Oxidative Stress, Central Neurotransmitters, and c-Fos Protein Expression in Rats" Molecules 25, no. 7: 1575. https://doi.org/10.3390/molecules25071575

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