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
AUTHORS (7)
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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