School of Bioscience and Biotechnology, Tokyo University of Technology, Hachioji, Tokyo, Japan.
Redox Rep. 2009;14(6):251-8. doi: 10.1179/135100009X12525712409779.
The free radical scavenger 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) has been used to treat acute brain infarction in Japan since 2001. To obtain direct evidence that edaravone serves as an antioxidant in vivo, four groups of rats were prepared: (i) an ischemia/reperfusion (I/R) group receiving 2 h occlusion-reperfusion of the middle cerebral artery; (ii) a single administration group treated by intravenous infusion of edaravone (3 mg/kg) immediately after I/R; (iii) a repeated treatment group receiving twice daily edaravone administration for 14 days; and (iv) a sham operation group without occlusion. Repeated treatment with edaravone significantly improved the neurological symptoms and impairment of motor function as compared to the I/R group, while single administration demonstrated limited efficacy. No significant differences in plasma antioxidants such as ascorbate, urate, and vitamin E, or in redox status of coenzyme Q(9) were observed among the four groups. In contrast, the plasma content of oleic acid in the total free fatty acids (percentage 18:1) was significantly increased in the I/R group for 7 days as compared to the sham operation group. Oleic acid was produced from stearic acid by the action of stearoyl-CoA desaturase to compensate for the oxidative loss of polyunsaturated fatty acids. The above results suggest that cellular oxidative damage in the rat brain is evident for at least 7 days after I/R. Repeated treatment suppressed the percentage 18:1 increment, while the single administration did not, which is consistent with the limited efficacy of single administration.
自由基清除剂 3-甲基-1-苯基-2-吡唑啉-5-酮（依达拉奉）自 2001 年起在日本被用于治疗急性脑梗死。为了获得依达拉奉在体内作为抗氧化剂的确切证据，我们准备了四组大鼠：（i）缺血/再灌注（I/R）组，接受大脑中动脉 2 小时闭塞再灌注；（ii）单次给药组，在 I/R 后立即通过静脉输注依达拉奉（3mg/kg）进行治疗；（iii）重复治疗组，每天两次给予依达拉奉治疗 14 天；（iv）假手术组，不进行闭塞。与 I/R 组相比，重复治疗依达拉奉显著改善了神经症状和运动功能障碍，而单次给药疗效有限。四组之间血浆抗氧化剂（如抗坏血酸、尿酸和维生素 E）或辅酶 Q(9)的氧化还原状态没有明显差异。相反，与假手术组相比，I/R 组在 7 天内总游离脂肪酸（18:1%）中的油酸含量显著增加。油酸是由硬脂酰辅酶 A 去饱和酶作用于硬脂酸生成的，以补偿多不饱和脂肪酸的氧化损失。上述结果表明，大鼠脑内细胞氧化损伤在 I/R 后至少持续 7 天。重复治疗抑制了 18:1%的增量，而单次给药则没有，这与单次给药的疗效有限是一致的。
