Search Results (3)

Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: These findings emphasize the importance of dose optimization in antioxidant-based epilepsy treatments and highlight the potential of MitoCur as a targeted therapeutic option. Full article

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. Full article

Mitocurcumin (a triphenylphosphonium curcumin derivative) was previously reported as a selective antitumoral compound on different cellular lines, as well as a potent bactericidal candidate. In this study, the same compound showed strong antimicrobial efficacy against different strains of methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration was identical for all tested strains (four strains of MRSA and one strain of methicillin-sensitive Staphylococcus aureus), suggesting a new mechanism of action compared with usual antibacterial agents. All tested strains showed a significant sensitivity in the low micromolar range for the curcumin-triphenylphosphonium derivative. This susceptibility was modulated by the menadione/glutathione addition (the addition of glutathione resulted in a significant increase in minimal inhibitory concentration from 1.95 to 3.9 uM, whereas adding menadione resulted in a decrease of 0.49 uM). The fluorescence microscopy showed a better intrabacterial accumulation for the new curcumin-triphenylphosphonium derivative compared with simple curcumin. The MitoTracker staining showed an accumulation of reactive oxygen species (ROS) for a S. pombe superoxide dismutase deleted model. All results suggest a new mechanism of action which is not influenced by the acquired resistance of MRSA. The most plausible mechanism is reactive oxygen species (ROS) overproduction after a massive intracellular accumulation of the curcumin-triphenylphosphonium derivative. Full article