Abstract

Objectives: 3-Methyl-1-phenyl-2-pyrazolin-5-one (edaravone) is used in clinical treatment of acute brain infarction to rescue the penumbra, based on its ability to prevent lipid peroxidation by scavenging lipid peroxyl radicals. Here, we show that edaravone also reacts with peroxynitrite to yield 4-NO-edaravone as the major product and 4-NO2-edaravone as a minor product.Results: We observed little formation of 3-methyl-1-phenyl-2-pyrazolin-4,5-dione (4-oxoedaravone) and its hydrate, 2-oxo-3-(phenylhydrazono)butanoic acid, which are the major free radical-induced oxidation products of edaravone, suggesting that free radicals are not involved in the reaction with peroxynitrite. The reaction of peroxynitrite with edaravone is approximately 30-fold greater than with uric acid, a physiological peroxynitrite scavenger (reaction rate k = 1.5 × 104 M−1 s−1 vs. 480 M−1 s−1).Discussion: These results suggest that edaravone functions therapeutically as a scavenger of peroxynitrite as well as lipid peroxyl radicals, which is consistent with a report that edaravone treatment reduced levels of 3-nitrotyrosine in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call