Behavioral and Biochemical Insights into the Therapeutic Potential of Mitocurcumin in a Zebrafish–Pentylenetetrazole (PTZ) Epilepsy Model

<b>Background/Objectives</b>: Epilepsy is a complex neurological disorder with a strong link to oxidative stress, which contributes to seizure susceptibility and neuronal damage. This study aims to investigate the effects of curcumin (Cur), sodium valproate (VPA), and mitocurcumin (MitoCur), a mitochondria-targeted curcumin, on behavioral and oxidative stress parameters in a zebrafish model of pentylenetetrazole (PTZ)-induced seizures. <b>Methods:</b> Adult zebrafish were exposed to two concentrations (0.25 and 0.5 µM for Cur and MitoCur; 0.25 and 0.5 mM for VPA). Behavioral assessments, including locomotion, spatial exploration, and directional movement, were conducted using EthoVision XT tracking software. Oxidative stress markers, including superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPx), and total antioxidant status (TAS), were analyzed in brain homogenates. <b>Results:</b> Behavioral analyses indicated dose-dependent effects, with higher doses generally reducing activity. MitoCur at 0.25 µM enhanced antioxidant defenses and reduced oxidative damage, while higher doses exhibited a pro-oxidant shift. VPA at 0.25 mM improved TAS without significantly altering MDA levels. <b>Conclusions:</b> These findings emphasize the importance of dose optimization in antioxidant-based epilepsy treatments and highlight the potential of MitoCur as a targeted therapeutic option.