Reactivity of an antioxidant, edaravone, with reactive oxygen species and its chemical repair properties against oxidative damage on DNA

Hata, Kuniki ; Lin, M.*; Yokoya, Akinari*; Fujii, Kentaro*; Yamashita, Shinichi*; Muroya, Yusa*; Katsumura, Yosuke*

Reactivity of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), which is known to show high antioxidative properties, with oxidative species, such as hydroxyl radical (OH) and azide radical (N), was investigated by a pulse radiolysis experiment, and generation behavior of edaravone radicals produced through these reactions were observed. It was shown that OH-adducts are produced by the reaction with OH in contrast to the other oxidative radicals, which react with edaravone by an electron transfer reaction. Chemical repair properties of edaravone against DNA lesions produced by reactions of DNA with oxidative species were also investigated by a pulse radiolysis experiment with deoxyguanosine monophosphate (dGMP) and a -radiolysis experiment with plasmid DNA solutions. It was observed that edaravone reduced dGMP radicals just after produced in a dilute aqueous solution and inhibited some base lesions on plasmid DNA more effectively than single strand breaks. These results show that edaravone may protect living system from oxidative stress, such as radiation, by not only scavenging oxidative species but also reducing precursors of DNA leisons.