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

Abstract

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, which poses a significant threat to human health. Increasing evidence indicates that the pathological mechanism of epilepsy is closely related to the presence of peroxynitrite (ONOO). To address this issue, we have developed a dual-molecule release precursor,, with different functional components, which consists of a responsive group, a reporter segment, and a drug molecule, for monitoring peroxynitrite. Based onassays,exhibits several advantages, including high specificity, a rapid response time (120 s), and a dual release function, and is not affected by other reactive oxygen species. When this precursor is activated by peroxynitrite, valproic acid (VPA) is released, which is a broad-spectrum antiepileptic drug that can reduce seizure occurrences; a near-infrared (NIR) reporter unit is formed synchronously using, and we successfully tracked the fluctuations of endogenous and exogenous ONOOin SH-SY5Y cells and achieved significant spatiotemporal resolution. Moreover,can clearly display the changes of endogenous ONOOin SH-SY5Y cells. Crucially,helps to perform fluorescence imaging of the ONOOconcentration in epilepsy models, while also reducing the seizure levels in mice and shortening their seizure latency, for the first time. These findings indicate thatprovides a promising tool for the diagnosis and treatment of epilepsy by imaging the fluctuations of ONOO, and offers a reliable method for studying the treatment of epilepsy.