Abstract
Chemical reactions in which radiation-induced radicals are quenched are generally expected as radioprotection mechanism of antioxidants. Specifically, it is reported that OH-scavenging and reduction of dGMP radicals in aqueous solutions (O'Neill, 1983). Similar processes are presumed in biological systems as well. Edaravone is an antioxidant, which is known to inhibit dysfunction resulted from attacks of ROS when brain infarct develops. Edaravone also exerts radioprotection effects in mice by administering edaravone of 450 mg/kg bw before X-ray irradiation (Anzai, 2004). Radioresistance of the mice treated with edaravone was exhibited by a factor of 1.3 compared to that of control mice. At the condition, scavenging capacity of edaravone for OH radicals was about 107 s-1, which is 20 times as low as that of intracellular molecules. Some peroxyl and sugar radicals on DNA were reported to have long lifetime of several seconds (Hildebrand, 1997). These two facts indicate chemical repair property of edaravone functions mainly by reacting to these long-lived radicals "directly" in intracellular condition as well as OH-scavenging.
In this study, we focus the chemical repair of edaravone. When edaravone works simply as an OH scavenger in dilute aqueous solution, yields of single strand break (SSB) and those of base lesions produced by attack of OH radical should decrease at the same rate. If chemical repair of edaravone works, the decreasing rate of these lesions may change due to the difference of accessibility of edaravone to each lesion sites. In order to confirm the chemical repair of edaravone by measuring the decreasing rate, we measured the yields of SSBs and base lesions visualized by converting to SSBs using enzymatic treatment. The yield of SSB was analyzed by electrophoresis of γ-ray irradiated diluted solution of 10 ng/μl plasmid DNA containing edaravone. We will discuss the radioprotection mechanism of edaravone base on those DNA damage protection efficiencies.
