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

Alaa Alachkar, Sheikh Azimullah, Mohamed Lotfy, Ernest Adeghate, Shreesh K. Ojha, Rami Beiram, Dorota Łażewska, Katarzyna Kieć-Kononowicz, Bassem Sadek

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1575
JournalMolecules
Volume25
Issue number7
DOIs
Publication statusPublished - 2020

Keywords

  • AChE activity
  • Antagonist
  • C-Fos protein expression
  • Histamine H3 receptor
  • Memory impairment
  • Neuroprotection
  • Oxidative stress
  • PTZ-kindling
  • Rats

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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