ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1621729
Neuroprotective and anticonvulsant effect of trimetazidine in a PTZ-kindling model of mice through modulation of the IL-1β/IL-1R1 and HMGB-1/TLR-4 axis
Provisionally accepted- 1Jamia Hamdard University, New Delhi, India
- 2University college of medical sciences, New Delhi, India
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Background: Epilepsy is a chronic and complex brain disorder characterized by frequent seizures, cognitive impairments, neuroinflammation, oxidative stress, and imbalances in neurotransmitters. Developing an effective therapeutic intervention to target these pathological interventions remains a challenge. Trimetazidine (TMZ), the most commonly known antiischemic agent, has emerged as a promising candidate for its role in epilepsy due to its diverse mechanisms of action. This study investigates the neuroprotective, anticonvulsant, antiinflammatory, antioxidant, and neuromodulatory effects of TMZ in managing epilepsy.Methods: Kindling was induced by administering Pentylenetetrazole (30 mg/kg, i.p) to Swiss albino mice on every alternate day; TMZ (5, 10, and 20 mg/k p.o) or sodium valproate (200 mg/kg p.o) was given for 5 weeks. Seizure severity was assessed on the Racine scale, and cognitive function and learning were evaluated using the elevated plus maze and the passive avoidance apparatus. Muscle strength was measured using the rotarod test. Neuroinflammatory biomarkers (IL-1β, IL-1R1, IL-6, NF-κB, TNF-α, HMGB-1, TLR-4), oxidative stress markers (MDA, GSH, SOD, catalase), and neurotransmitter (GABA, glutamate, dopamine, serotonin) levels were estimated in the hippocampus and cerebral cortex using commercially available sandwich ELISA kits.Results: TMZ, primarily at 10 and 20 mg/kg, significantly reduced seizure scores and improved the transfer latency, step-down latency, and motor abilities in the PTZ-kindled animals. It significantly reduced proinflammatory molecules IL-1β, IL-1R1, IL-6, NF-κB, TNF-α, HMGB-1, TLR-4. Additionally, it increased antioxidant enzyme activity (GSH, SOD, catalase) while lowering MDA levels and restoring GABA, dopamine, and serotonin levels, as well as suppressing glutamate levels, comparable to VPA at 200 mg/kg/day p.o.TMZ, at doses of 10 and 20 mg/kg p.o., demonstrated anticonvulsant and antioxidant activity, suppressed kindling progression, and restored neurotransmitter balance.Furthermore, TMZ has shown anti-inflammatory activity against neuroinflammation during epilepsy.
Keywords: Epilepsy, Cognition, Trimetazidine, PTZ-kindling, Neuroinflammation, Oxidative Stress, neurotransmitters
Received: 01 May 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Ahmad, Samim, Jain, Vohora and .. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Nidhi ., Jamia Hamdard University, New Delhi, India
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