Peroxynitrite-Activated Valproic Acid Precursor for Monitoring Oxidative Stress and Reducing Epileptic Seizures in an...

Area of Science:

• Biomedical Engineering
• Neuroscience
• Chemical Biology

Background:

• Epilepsy is a neurological disorder linked to peroxynitrite (ONOO-) levels.
• Current diagnostic and therapeutic strategies for epilepsy require improvement.

Purpose of the Study:

• To develop and evaluate a dual-molecule release precursor, DVN, for monitoring peroxynitrite in epilepsy.
• To assess DVN's efficacy in imaging peroxynitrite and its therapeutic potential in epilepsy models.

Main Methods:

• DVN was designed as a precursor releasing valproic acid (VPA) and a near-infrared (NIR) reporter upon peroxynitrite activation.
• In vitro assays evaluated DVN's specificity, response time, and stability against reactive oxygen species.
• DVN's performance was tested in SH-SY5Y cells for peroxynitrite imaging and in mouse models for therapeutic effects.

Main Results:

• DVN demonstrated high specificity, rapid response (120s), and dual release function, unaffected by other reactive oxygen species.
• DVN successfully tracked endogenous and exogenous peroxynitrite in SH-SY5Y cells with high spatiotemporal resolution.
• DVN facilitated fluorescence imaging of peroxynitrite in epilepsy models, reduced seizure severity, and shortened seizure latency in mice.

Conclusions:

• DVN serves as a promising tool for epilepsy diagnosis by imaging peroxynitrite fluctuations.
• DVN offers a novel therapeutic approach for epilepsy, demonstrated by reduced seizure activity in mice.
• This study provides a reliable method for investigating epilepsy treatment through peroxynitrite monitoring.