Öz
Aim: This research sought to evaluate the anticonvulsant properties of Felodipine in a rat model of pentylenetetrazol (PTZ)-induced seizures, with a particular focus on its modulatory effects on neuroinflammatory responses and oxidative stress biomarkers.
Material and Method: The entirety of 48 male Wistar rats were separated into two main groups for behavioral and electrophysiological assessments. The anticonvulsant properties of Felodipine at dosages of 10 mg/kg and 20 mg/kg were evaluated according to seizure severity, using Racine’s Convulsion Scale and the latency to the First Myoclonic Jerk (FMJ). Electroencephalographic (EEG) recordings were analyzed to measure epileptiform activity by assessing the proportion of spike-wave discharges. Neuroinflammatory and oxidative stress markers, namely tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA), were quantified in brain tissue using Enzyme-linked immunosorbent assay (ELISA) and Thiobarbituric Acid Reactive Substances (TBARS) tests, respectively. A p-value of less than 0.05 was deemed statistically significant.
Results: Felodipine significantly decreased seizure intensity and prolonged FMJ start time relative to the PTZ and saline-treated cohorts (p<0.05). EEG recordings revealed a marked decrease in spike percentages in the Felodipine-treated groups. Furthermore, biochemical analyses demonstrated that Felodipine significantly reduced TNF-α and MDA levels, indicating its neuroprotective effects by mitigating neuroinflammation and oxidative stress.
Conclusion: The PTZ-induced seizure model showed that felodipine significantly reduced seizure activity, neuroinflammation, and oxidative stress, indicating robust anticonvulsant and neuroprotective benefits. Its favorable safety profile and dual-action mechanism targeting calcium channels and inflammatory pathways position it as a promising candidate for epilepsy management. Further studies are warranted to explore its long-term efficacy and potential in chronic epilepsy models.
Anahtar Kelimeler
Epilepsy felodipine calcium channel blockers neuroinflammation oxidative stress anticonvulsant therapy
Etik Beyan
The experimental protocol for this study was reviewed and approved by the Animal Ethics Committee of Science University. Date: 15.01.2023, number: 0123113305.
Kaynakça
- Zupan G, Herlinger M, Simonic A, et al. Effects of nimodipine, felodipine, and amlodipine on electroconvulsive shock-induced amnesia in rats. Eur J Pharmacol. 1996;310:103-6.
- Kamal JA, Nadig RS, Joseph T, David J. Effect of calcium channel blockers on experimentally induced seizures in rats. Indian J Exp Biol. 1990;28:605-8.
- Fadheel OQ, Saeed AM, Mohammed RK. Effect of felodipine against pilocarpine-induced seizures in rats. Int J Pharm Sci Rev Res. 2018;52:54-60.
- Saniya K, Patil BG, Madhavrao C, Prakash KG. Effect of calcium channel blockers on the seizures, oxidative stress, and histoarchitecture in the rats. J Pharmacol Pharmacother 2019;10:93-9.
- Yiu S, Knaus EE. Synthesis and biological evaluation of felodipine for anticonvulsant activity. J Med Chem. 1996;39:4576-82.
- Waciński P. Influence of felodipine on experimental seizures and activity of different antiepileptic drugs in mice. Pol J Pharmacol. 1998;50:23-9.
- Erbaş O, Solmaz V, Aksoy D. Inhibitor effect of dexketoprofen in rat model of pentylenetetrazol-induced seizures. Neurol Res. 2015;37:1096-101.
- Rogawski MA, Löscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci. 2004;5:553-64.
- Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 4th edition. London: Academic Press; 1998;136-42.
- Erdogan MA, Erdogan A, Erbas O. The anti-seizure effect of liraglutide on PTZ-induced convulsions through its anti-oxidant and anti-inflammatory properties. Neurochem Res. 2023;48:188-95.
- Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351-8.
- Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54.
- El-Azab MF, Moustafa YM. Influence of calcium channel blockers on anticonvulsant and antinociceptive activities of valproic acid in pentylenetetrazole-kindled mice. Pharmacol Rep. 2012;64:305-14.
- Vezzani A, Baram TZ. New roles for interleukin-1 Beta in the mechanisms of epilepsy. Epilepsy Curr. 2007;7:45-50.
- Aguiar CC, Almeida AB, Araújo PV, et al. Oxidative stress and epilepsy: literature review. Oxid Med Cell Longev. 2012;2012:795259.
- Ciancarelli I, Tozzi-Ciancarelli MG, Di Massimo C, et al. Flunarizine effects on oxidative stress in migraine patients. Cephalalgia. 2004;24:528-32.
- Aypak SÜ, İnci A. Reason for the ineffective treatment: P Glycoproteins. Bozok Tıp Derg. 2018;7:81-8.
- Yıldırım M, Değirmenci U, Yalın S. The role of inflammation in epilepsy. Mersin Univ Sag Bilim Derg. 2019;12:525-33.
- Hasan M, Pulman J, Marson AG. Calcium antagonists as an add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev. 2013;2013:CD002750.
- Ahmed N, Näsmän P, Wahlgren NG. Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. Stroke. 2000;31:1250-5.
- Jansone B, Kadish I, van Groen T, et al. A novel 1,4-dihydropyridine derivative improves spatial learning and memory and modifies brain protein expression in wild type and transgenic APP SweDI mice. PLoS One. 2015;10:e0127686.
Öz
Kaynakça
- Zupan G, Herlinger M, Simonic A, et al. Effects of nimodipine, felodipine, and amlodipine on electroconvulsive shock-induced amnesia in rats. Eur J Pharmacol. 1996;310:103-6.
- Kamal JA, Nadig RS, Joseph T, David J. Effect of calcium channel blockers on experimentally induced seizures in rats. Indian J Exp Biol. 1990;28:605-8.
- Fadheel OQ, Saeed AM, Mohammed RK. Effect of felodipine against pilocarpine-induced seizures in rats. Int J Pharm Sci Rev Res. 2018;52:54-60.
- Saniya K, Patil BG, Madhavrao C, Prakash KG. Effect of calcium channel blockers on the seizures, oxidative stress, and histoarchitecture in the rats. J Pharmacol Pharmacother 2019;10:93-9.
- Yiu S, Knaus EE. Synthesis and biological evaluation of felodipine for anticonvulsant activity. J Med Chem. 1996;39:4576-82.
- Waciński P. Influence of felodipine on experimental seizures and activity of different antiepileptic drugs in mice. Pol J Pharmacol. 1998;50:23-9.
- Erbaş O, Solmaz V, Aksoy D. Inhibitor effect of dexketoprofen in rat model of pentylenetetrazol-induced seizures. Neurol Res. 2015;37:1096-101.
- Rogawski MA, Löscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci. 2004;5:553-64.
- Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 4th edition. London: Academic Press; 1998;136-42.
- Erdogan MA, Erdogan A, Erbas O. The anti-seizure effect of liraglutide on PTZ-induced convulsions through its anti-oxidant and anti-inflammatory properties. Neurochem Res. 2023;48:188-95.
- Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351-8.
- Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54.
- El-Azab MF, Moustafa YM. Influence of calcium channel blockers on anticonvulsant and antinociceptive activities of valproic acid in pentylenetetrazole-kindled mice. Pharmacol Rep. 2012;64:305-14.
- Vezzani A, Baram TZ. New roles for interleukin-1 Beta in the mechanisms of epilepsy. Epilepsy Curr. 2007;7:45-50.
- Aguiar CC, Almeida AB, Araújo PV, et al. Oxidative stress and epilepsy: literature review. Oxid Med Cell Longev. 2012;2012:795259.
- Ciancarelli I, Tozzi-Ciancarelli MG, Di Massimo C, et al. Flunarizine effects on oxidative stress in migraine patients. Cephalalgia. 2004;24:528-32.
- Aypak SÜ, İnci A. Reason for the ineffective treatment: P Glycoproteins. Bozok Tıp Derg. 2018;7:81-8.
- Yıldırım M, Değirmenci U, Yalın S. The role of inflammation in epilepsy. Mersin Univ Sag Bilim Derg. 2019;12:525-33.
- Hasan M, Pulman J, Marson AG. Calcium antagonists as an add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev. 2013;2013:CD002750.
- Ahmed N, Näsmän P, Wahlgren NG. Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. Stroke. 2000;31:1250-5.
- Jansone B, Kadish I, van Groen T, et al. A novel 1,4-dihydropyridine derivative improves spatial learning and memory and modifies brain protein expression in wild type and transgenic APP SweDI mice. PLoS One. 2015;10:e0127686.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sinirbilim (Diğer), Tıbbi Fizyoloji (Diğer) |
| Bölüm | Özgün Makaleler |
| Yazarlar | |
| Yayımlanma Tarihi | |
| Gönderilme Tarihi | 4 Mart 2025 |
| Kabul Tarihi | 7 Mayıs 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 7 Sayı: 3 |
Chief Editors
Assoc. Prof. Zülal Öner
Address: İzmir Bakırçay University, Department of Anatomy, İzmir, Turkey
Assoc. Prof. Deniz Şenol
Address: Düzce University, Department of Anatomy, Düzce, Turkey
Editors
Assoc. Prof. Serkan Öner
İzmir Bakırçay University, Department of Radiology, İzmir, Türkiye
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