A Study on the free radical scavenging mechanism of edaravone

Hata, Kuniki ; Katsumura, Yosuke; Lin, M.; Muroya, Yusa*; Fu, H.*; Yamashita, Shinichi; Kudo, Hisaaki*; Nakagawa, Keiichi*; Nakagawa, Hidehiko*

Edaravone or RadiCut, 3-methyl-1-phenyl-2-pyrazolin-5-one, is a developed free radical scavenger that has been approved in Japan as a neuroprotective drug since 2001. For its antioxidative property and high reactivity with free radicals, edaravone has been expected as a radioprotector. In the last decade, the reactivity of edaravone with peroxyl radicals or some enzymes which induce oxidizing reactions, as well as the antioxidative properties of edaravone, have been extensively investigated. However, there are only a few reports on the measurements of the reactivity of edaravone towrads OH radical, although OH radical is thought to be a main factor of indirect radiation induced damages. In this work, we measured the reactivity of edaravone with OH radical, and elucidated its reaction mechanism. The reactions of edaravone and its model compound (1,3-dimethyl-2-pyrazolin-5-one) with OH radical or other oxidizing radicals were measured by pulse radiolysis techniques. The result shows that the intermediate radical produced by the reaction of edaravone with OH radical was spectroscopically different from that by the reactions with other radicals. On the other hand, for 1,3-dimethyl-2-pyrazolin-5-one, the intermediate radical by the reaction with OH radical is similar to that by the reaction with other oxidizing radical. All these strongly suggest that the phenyl group of edaravone plays an important role on the reaction with OH radical. Thus, in contrast to the previous reports in which the oxidation by OH radical was assumed to be through electron transfer or hydrogen abstraction from pyrazolin-5-one, the formation of OH adducts is crucial for the reaction of edaravone towards OH radical.