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CC BY 4.0 · Arq Neuropsiquiatr 2022; 80(12): 1220-1226
DOI: 10.1055/s-0042-1758754
Original Article

The antiinflammatory and electrophysiological effects of fingolimod on penicillin-induced rats

Os efeitos antiinflamatórios e eletrofisiológicos do fingolimode em ratos induzidos pela penicilina
Canan Akünal Türel 
1   Bolu Abant İzzet Baysal University School of Medicine, Department of Neurology, Bolu, Turkey.
,
Hümeyra Çelik 
2   Bolu Abant İzzet Baysal University School of Medicine, Department of Physiology, Bolu, Turkey.
,
İbrahim Ethem Torun 
2   Bolu Abant İzzet Baysal University School of Medicine, Department of Physiology, Bolu, Turkey.
,
Ayhan Çetinkaya 
2   Bolu Abant İzzet Baysal University School of Medicine, Department of Physiology, Bolu, Turkey.
,
İdris Türel 
3   Bolu Abant İzzet Baysal University School of Medicine, Department of Pharmacology, Bolu, Turkey.
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Abstract

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.

Resumo

Antecedentes O fato de a inflamação desencadear crises epilépticas traz à mente as propriedades antiepilépticas dos anti-inflamatórios.

Objetivo Investigar os efeitos eletrofisiológicos e anti-inflamatórios do fingolimode em um modelo experimental de crise epiléptica aguda induzida por penicilina em ratos.

Métodos Trinta e dois ratos Wistar machos foram divididos em quatro grupos: controle (penicilina), controle positivo (penicilina + diazepam [5 mg/kg]), droga (penicilina + fingolimode [0,3 mg/kg]) e grupo sinergia (penicilina + diazepam + fingolimode). Os animais foram anestesiados com uretano, e a atividade epileptiforme foi induzida por injeção intracortical de penicilina (500.000 UI). Após registro eletrofisiológico por 125 minutos, IL-1β, TNF-α e IL-6 foram avaliados por ELISA no soro dos animais sacrificados.

Resultados Durante o experimento, ocorreram mortes de animais no grupo sinérgico devido ao efeito cronotrópico negativo sinérgico do diazepam e do fingolimode. Embora não seja estatisticamente significativo, o fingolimode causou uma ligeira diminuição na atividade pico-onda e nas amplitudes pico no modelo de convulsão aguda induzida pela penicilina (p > 0,05). O fingolimode diminuiu a IL-1β sérica (p < 0,05); fingolimode e diazepam juntos reduziram a IL-6 (p < 0,05), mas não foi observada alteração nos valores séricos de TNF-α.

Conclusão Pensa-se que o efeito anticonvulsivante leve de uma dose única de fingolimode será mais proeminente em aplicações crônicas e em avaliações de tecidos centrais. Além disso, o uso concomitante de fingolimode e diazepam é considerado contraindicado devido ao efeito inotrópico negativo sinérgico.

Keywords

Rats - Fingolimod Hydrochloride - Anti-Inflammatory Agents - Electrophysiology - Seizures - Epilepsy - Penicillins

Palavras-chave

Ratos - Cloridrato de Fingolimode - Anti-Inflamatórios - Eletrofisiologia - Convulsões - Epilepsia - Penicilinas

Authors' Contributions

CAT, AÇ, IT: investigation; AÇ, IET, CT: method; İET, HÇ, İT: analysis; CT, HÇ, İET: writing; CT, İT: funding; AÇ: supervisor.




Publication History

Received: 08 November 2021

Accepted: 16 March 2022

Article published online:
29 December 2022

© 2022. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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