In Vivo Radioprotection of Mice by 3-Methyl-1-phenyl-2-pyrazolin-5-one (Edaravone; Radicut®), a Clinical Drug

Male 0301 basic medicine Mice, Inbred C3H Dose-Response Relationship, Drug Survival X-Rays Dose-Response Relationship, Radiation Radiation-Protective Agents Radiation Tolerance Survival Analysis Body Temperature 3. Good health Mice 03 medical and health sciences Radiation Protection Treatment Outcome Pharmaceutical Preparations Edaravone Animals Radiation Injuries Antipyrine Injections, Intraperitoneal Whole-Body Irradiation
DOI: 10.1269/jrr.45.319 Publication Date: 2004-08-10T06:06:19Z
ABSTRACT
Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut) is a brain-protecting agent used clinically to treat acute ischemic stroke with a reaction mechanism of free radical scavenging. Since the initial stage of radiation damage involves the formation of free radicals, edaravone is expected to be effective in preventing lethal damage from ionizing radiation. In the present study, we used mice to examine in vivo the radioprotective effect of edaravone on whole body X-ray irradiation. A solution of edaravone was administered intraperitoneally to C3H mice (male, 10 weeks old), and they were irradiated with a total dose of 8.0 Gy. Edaravone exhibited dose-dependent and injection time-dependent radioprotection. When injected 30 min before the X-ray irradiation, it had the greatest radioprotective effect, whereas an injection after the irradiation showed no protective effect. The LD(50/30) was about 8.8 Gy for edaravone-injected mice and 6.6 Gy for control mice, yielding a DRF for edaravone (450 mg/kg bw) of 1.3. Edaravone decreased the body temperature transiently about 3-6C, but this did not seem to be responsible for the radioprotection. Since the radioprotection was observed only when the reagent was administered before the irradiation, the primary action of edaravone might be the quenching of free radicals with a short lifetime generated by the irradiation.
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