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

• Published in: Journal of radiation research Vol. 56; no. 1; pp. 59 - 66
• Main Authors: Hata, Kuniki, Urushibara, Ayumi, Yamashita, Shinichi, Lin, Mingzhang, Muroya, Yusa, Shikazono, Naoya, Yokoya, Akinari, Fu, Haiying, Katsumura, Yosuke
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.01.2015
• Subjects: Adducts; Antioxidants (Nutrients); Antipyrine - analogs & derivatives; Antipyrine - chemistry; Ascorbic acid; Base Sequence - radiation effects; Biology; Breaking; DNA; DNA Adducts - chemistry; DNA Adducts - radiation effects; DNA Damage - drug effects; DNA Repair - drug effects; Dose-Response Relationship, Radiation; Edaravone; Electron transport; Free Radical Scavengers - chemistry; Gamma rays; Hydroxides; Hydroxyl Radical - chemistry; Hydroxyl Radical - radiation effects; Hydroxyl radicals; Irradiation; Lesions; Molecular Sequence Data; Oxidation-Reduction - radiation effects; Plasmid DNA; Plasmids - chemistry; Plasmids - genetics; Plasmids - radiation effects; Pulse Radiolysis; Radiation Dosage; Radiolysis; Repair; pulse radiolysis; antioxidant; edaravone (Radicut®); chemical repair
• ISSN: 0449-3060; 1349-9157
• DOI: 10.1093/jrr/rru079

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.