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Anti-Epileptic Activity of Mitocurcumin in a Zebrafish–Pentylenetetrazole (PTZ) Epilepsy Model

Authors :
Alin Dumitru Ciubotaru
Carmen-Ecaterina Leferman
Bogdan-Emilian Ignat
Anton Knieling
Delia Lidia Salaru
Dana Mihaela Turliuc
Liliana Georgeta Foia
Lorena Dima
Bogdan Minea
Luminita Diana Hritcu
Bogdan Ionel Cioroiu
Laura Stoica
Ioan-Adrian Ciureanu
Alin Stelian Ciobica
Bogdan Alexandru Stoica
Cristina Mihaela Ghiciuc
Source :
Pharmaceuticals, Vol 17, Iss 12, p 1611 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Background/Objectives: Ongoing challenges in epilepsy therapy warrant research on alternative treatments that offer improved efficacy and reduced side effects. Designed to enhance mitochondrial targeting and increase bioavailability, mitocurcumin (MitoCur) was evaluated for the first time as an antiepileptic agent, with curcumin (Cur) and sodium valproate (VPA), a standard antiepileptic drug, included for comparison. This study investigated the effects on seizure onset, severity, and progression in a zebrafish model of pentylenetetrazole (PTZ)-induced seizures and measured the concentrations of the compounds in brain tissue. Methods: Zebrafish were pre-treated with MitoCur and Cur (both at 0.25 and 0.5 µM doses) and VPA (0.25 and 0.5 mM) and observed for four minutes to establish baseline locomotor behavior. Subsequently, the animals were exposed to a 5 mM PTZ solution for 10 min, during which seizure progression was observed and scored as follows: 1—increased swimming; 2—burst swimming, left and right movements; 3—circular movements; 4—clonic seizure-like behavior; 5—loss of body posture. The studied compounds were quantified in brain tissue through HPLC and LC-MS. Results: Compared to the control group, all treatments reduced the distance moved and the average velocity, without significant differences between compounds or doses. During PTZ exposure, seizure latencies revealed that all treatments effectively delayed seizure onset up to score 4, demonstrating efficacy in managing moderate seizure activity. Notably, MitoCur also provided significant protection against the most severe seizure score (score 5). Brain tissue uptake analysis indicated that MitoCur achieved higher concentrations in the brain compared to Cur, at both doses. Conclusions: These results highlight the potential of MitoCur as a candidate for seizure management.

Details

Language :
English
ISSN :
14248247
Volume :
17
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Pharmaceuticals
Publication Type :
Academic Journal
Accession number :
edsdoj.64ece0321f11431a9f69c35134cd1916
Document Type :
article
Full Text :
https://doi.org/10.3390/ph17121611