title: Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA.
abstract: Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 × 10(8) dm(3) mol(-1) s(-1) and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10-1000 μmol dm(-3)) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid.
authors.affiliation: Department of Nuclear Engineering and Management, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakatashirane, Tokai-mura, Naka-gun, Ibaraki 319-1195, Japan hata.kuniki@jaea.go.jp.
authors.forename: Kuniki
authors.initials: K
authors.lastname: Hata
authors.affiliation: Laboratory of Radiation Biology, Osaka Prefecture University, 1-2 Gakuenchou, Naka-ku, Sakai-shi, Osaka 599-8570, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Urushibara
authors.affiliation: Nuclear Professional School, School of Engineering, The University of Tokyo, 2-22 Shirakatashirane, Tokai-mura, Nakagun, Ibaraki 319-1188, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: School of Nuclear Science and Technology, University of Science and Technology of China, 96 JinZhai Road, Hefei, Anhui 230026, P.R. China.
authors.forename: Mingzhang
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Beam Materials Science, Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki-shi, Osaka 567-0047, Japan.
authors.forename: Yusa
authors.initials: Y
authors.lastname: Muroya
authors.affiliation: Quantum Beam Science Directorate, Japan Atomic Energy Agency, 8-1-7 Umemidai, Kizukawa-shi, Kyoto 619-0215, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Shikazono
authors.affiliation: Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakatashirane, Tokai-mura, Naka-gun, Ibaraki 319-1195, Japan.
authors.forename: Akinari
authors.initials: A
authors.lastname: Yokoya
authors.affiliation: Shanghai Institute of Applied Physcs, Chinese Academy of Science, Shanghai 201800, P.R. China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Fu
authors.affiliation: Department of Nuclear Engineering and Management, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan Nuclear Professional School, School of Engineering, The University of Tokyo, 2-22 Shirakatashirane, Tokai-mura, Nakagun, Ibaraki 319-1188, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Katsumura
mesh_terms: D000983:Antipyrine / Q000031:analogs & derivatives* / Q000737:chemistry; D001483:Base Sequence / Q000528:radiation effects; D018736:DNA Adducts / Q000737:chemistry / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004307:Dose-Response Relationship, Radiation; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry / Q000528:radiation effects; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction / Q000528:radiation effects; D010957:Plasmids / Q000737:chemistry* / Q000235:genetics / Q000528:radiation effects*; D011675:Pulse Radiolysis; D011829:Radiation Dosage
chemical_list: D018736:DNA Adducts; D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D000077553:Edaravone; D000983:Antipyrine
keywords: antioxidant; chemical repair; edaravone (Radicut®); pulse radiolysis