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

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut(R)) 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 b...

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Published in:	JOURNAL OF RADIATION RESEARCH Vol. 45; no. 2; pp. 319 - 323
Main Authors:	Anzai, Kazunori, Furuse, Masako, Yoshida, Akira, Matsuyama, Azusa, Moritake, Takashi, Tsuboi, Koji, Ikota, Nobuo
Format:	Journal Article
Language:	English
Published:	England THE JAPAN RADIATION RESEARCH SOCIETY 01-06-2004 Oxford University Press
Subjects:	Animals Antipyrine - administration & dosage Antipyrine - analogs & derivatives Body Temperature - radiation effects Dose-Response Relationship, Drug Dose-Response Relationship, Radiation Edaravone Injections, Intraperitoneal Ionizing radiation Ischemia Male Mice Mice, Inbred C3H Pharmaceutical Preparations - administration & dosage Radiation Injuries - etiology Radiation Injuries - prevention & control Radiation Protection - methods Radiation Tolerance - drug effects Radiation-Protective Agents - administration & dosage Stroke Survival Survival Analysis Treatment Outcome Whole-Body Irradiation X-Rays
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Summary:	Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut(R)) 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 LD50/30 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 3-6℃, 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.
ISSN:	0449-3060 1349-9157
DOI:	10.1269/jrr.45.319