In vivo radioprotection of mice by 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone; Radicut®), a clinical drug
In vivo radioprotection of mice by 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone; Radicut®), a clinical drug
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DOI：
10.1269/jrr.45.319
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发表时间：
2004-06-01
影响因子：
2
通讯作者：
Ikota, N
中科院分区：
文献类型：
--
作者：
Anzai, K;Furuse, M;Ikota, N
依达拉奉（3 -甲基-1-苯基-2-吡唑啉-5-酮; Radicut（R））是临床上用于治疗急性缺血性中风的脑保护剂，具有清除自由基的反应机制。由于辐射损伤的初始阶段涉及自由基的形成，因此预期依达拉奉可有效预防电离辐射的致死性损伤。在本研究中，我们使用小鼠体内检查依达拉奉对全身X射线照射的辐射防护作用。将依达拉奉溶液腹膜内给予C3 H小鼠（雄性，10周龄），并用8.0戈伊的总剂量对它们进行照射。依达拉奉具有剂量依赖性和注射时间依赖性的放射防护作用。当在X射线照射前30分钟注射时，其具有最大的辐射防护效果，而在照射后注射没有显示出防护效果。依达拉奉注射小鼠的LD 50/30约为8.8戈伊，对照小鼠为6.6戈伊，得出依达拉奉（450 mg/kg bw）的DRF为1.3。依达拉奉可使体温一过性降低3- 6 ℃，但这似乎不是其辐射防护作用的原因。由于仅在照射前给予试剂时观察到放射保护作用，依达拉奉的主要作用可能是淬灭照射产生的寿命较短的自由基。
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 3-6degreesC, 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.