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The antiinflammatory and electrophysiological effects of fingolimod on penicillin-induced rats
Canan Akünal Türel1, Hümeyra Çelik2, İbrahim Ethem Torun2
1Bolu Abant İzzet Baysal University School of Medicine, Department of Neurology, Bolu, Turkey.
Background:
The fact that inflammation triggers epileptic seizures brings to mind the antiepileptic properties of anti-inflammatory drugs.
Objective:
To investigate the electrophysiological and anti-inflammatory effects of fingolimod on an experimental penicillin-induced acute epileptic seizure model in rats.
Methods:
Thirty-two male Wistar rats were divided into four groups: control (penicillin), positive control (penicillin + diazepam [5 mg/kg]), drug (penicillin + fingolimod [0.3 mg/kg]) and synergy group (penicillin + diazepam + fingolimod). The animals were anesthetized with urethane, and epileptiform activity was induced by intracortical injection of penicillin (500,000 IU). After electrophysiological recording for 125 minutes, IL-1β, TNF-α, and IL-6 were evaluated by ELISA in the serum of sacrificed animals.
Results:
During the experiment, animal deaths occurred in the synergy group due to the synergistic negative chronotropic effect of diazepam and fingolimod. Although not statistically significant, fingolimod caused a slight decrease in spike-wave activity and spike amplitudes in the acute seizure model induced by penicillin (p > 0.05). Fingolimod decreased serum IL-1β (p < 0.05); fingolimod and diazepam together reduced IL-6 (p < 0.05), but no change was observed in serum TNF-α values.
Conclusion:
Even in acute use, the spike-wave and amplitude values of fingolimod decrease with diazepam, anticonvulsant and anti-inflammatory effects of fingolimod will be more prominent in chronic applications and central tissue evaluations. In addition, concomitant use of fingolimod and diazepam is considered to be contraindicated due to the synergistic negative inotropic effect.
Insights
Fingolimod showed mild anticonvulsant effects and reduced inflammation in a rat seizure model. However, combining it with diazepam caused adverse effects, suggesting caution for chronic use and further research into its anti-inflammatory and anticonvulsant properties.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Inflammation is a known trigger for epileptic seizures.
- Anti-inflammatory drugs may possess antiepileptic properties.
Purpose of the Study:
- To evaluate the electrophysiological and anti-inflammatory effects of fingolimod.
- To investigate fingolimod's efficacy in a penicillin-induced acute epileptic seizure model in rats.
Main Methods:
- Thirty-two rats were divided into control, diazepam, fingolimod, and combination groups.
- Epileptiform activity was induced via intracortical penicillin injection.
- Electrophysiological recordings and serum cytokine analysis (IL-1β, TNF-α, IL-6) were performed.
Main Results:
- Fingolimod slightly reduced seizure activity and spike amplitudes (p>0.05).
- Fingolimod significantly decreased serum IL-1β (p<0.05).
- Fingolimod and diazepam combination reduced IL-6 (p<0.05) but caused mortality due to synergistic negative chronotropic effects.
Conclusions:
- Fingolimod demonstrates potential anticonvulsant and anti-inflammatory effects, likely more pronounced in chronic applications and central tissue analysis.
- Concomitant use of fingolimod and diazepam is contraindicated due to adverse synergistic effects.
- Further research is warranted to explore fingolimod's therapeutic potential in epilepsy.
