Repeated edaravone treatment reduces oxidative cell damage in rat brain induced by middle cerebral artery occlusion.
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.
Yamamoto
Yorihiro
Y
School of Bioscience and Biotechnology, Tokyo University of Technology, Hachioji, Tokyo, Japan. junkan@bs.teu.ac.jp
Yanagisawa
Makoto
M
Tak
Nyou Wei
NW
Watanabe
Kazutoshi
K
Takahashi
Chizuko
C
Fujisawa
Akio
A
Kashiba
Misato
M
Tanaka
Masahiko
M
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D008297:Male; D015394:Molecular Structure; D009483:Neuropsychological Tests; D019301:Oleic Acid / Q000097:blood; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D015415:Biomarkers; D016166:Free Radical Scavengers; D019301:Oleic Acid; D000077553:Edaravone; D000983:Antipyrine