Jarrar, Qais and Ayoub, Rami and Jarrar, Yazun and Aburass, Hadeel and Goh, Khang Wen and Ardianto, Chrismawan and Long, Chiau Ming * and Moshawih, Said and Alfaqih, Hussain (2023) Flumazenil Pretreatment Reduces Mefenamic Acid-Induced Central Nervous System Toxicity in Mice. Journal of Integrative Neuroscience, 22 (4). ISSN 1757-448X
Full text not available from this repository. (Request a copy)Abstract
Background: Mefenamic acid (MFA), a common analgesic, causes central nervous system (CNS) toxicity at high doses with a proposed activity on the Gamma-aminobutyric acid (GABA) system. However, it remains unknown whether flumazenil (FMZ), a GABA type A receptor (GABAAR) antagonist, can reverse MFA toxicity. Methods: The behavioral and neurophysiological effects of MFA were investigated in mice with and without FMZ pre-treatment. The elevated zero maze (EZM) and marble burying tests were used to assess anxiety-like behaviors and burying activities, respectively. The standard bar test was used to evaluate catalepsy, while the actophotometer test was used to measure locomotor activity. Seizure intensity was scored, and fatalities were counted. Results: Without FMZ pre-treatment, MFA induced behavioral and neurophysiological effects in a dose-dependent manner as follows: At a dose of 20 mg/kg, i.p, MFA-treated mice exhibited anxiety-like behaviors, which was determined by a significant increase in the time spent in the closed areas and a significant decrease in the number of entries to the open areas of the EZM apparatus. These mice also showed a significant decrease in the burying activity, manifested as a significant decrease in the number of buried marbles. At 40 mg/kg, i.p., MFA-treated mice showed catalepsy that was associated with a significant decrease in locomotor activity. At a dose of 80 mg/kg, i.p., mice developed fatal tonic-clonic seizures (seizure score = 4). Pre-treatment with FMZ (5 mg/kg, i.p.) significantly reversed the anxiety-like behaviors and restored marble-burying activity. Additionally, FMZ prevented catalepsy, significantly restored locomotor activity, reduced seizure intensity (seizure score = 0.3) and significantly reduced mortalities. Conclusions: The present study's findings indicate that activation of the GABAAR is involved in the CNS toxicity of MFA, and FMZ reverses MFA toxicity by interfering with this receptor.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GABA; anxiety; central nervous system; convulsions; gamma-aminobutyric acid type A receptors; neurological disease; psychiatric disease. |
| Subjects: | Q Science > QL Zoology Q Science > QM Human anatomy Q Science > QP Physiology R Medicine > RC Internal medicine |
| Divisions: | Others > Non Sunway Academics Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020] > Department of Medical Sciences |
| Depositing User: | Ms Yong Yee Chan |
| Related URLs: | |
| Date Deposited: | 25 Jul 2024 08:21 |
| Last Modified: | 25 Jul 2024 08:21 |
| URI: | http://eprints.sunway.edu.my/id/eprint/2890 |
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