The reaction rate of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186)) with hydroxyl radical.
The pyrazoline derivative edaravone is a potent hydroxyl radical scavenger that has been approved for attenuation of brain damage caused by ischemia-reperfusion. In the present work, we first determined the rate constant, k(r), at which edaravone scavenges radicals generated by a Fenton reaction in aqueous solution in the presence of the spin trap agent, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which competed with edaravone. We detected the edaravone radicals in the process of hydroxyl radical scavenging and found that edaravone reacts with hydroxyl radical around the diffusion limit (k(r)=3.0 x 10(10) M(-1) s(-1)). The EPR (electron paramagnetic resonance) spectrum of the edaravone radical was observed by oxidation with a horseradish peroxidase-hydrogen peroxide system using the fast-flow method. This radical species is unstable and changed to another radical species with time. In addition, it was found that edaravone consumed molecular oxygen when it was oxidized by horseradish peroxidase (HRP)-H(2)O(2) system, and that edaravone was capable of providing two electrons to the electrophiles. The possible mechanisms for oxidation of edaravone were investigated from these findings.
Abe
Shinji
S
Department of Pharmacology, The University of Tokushima School of Medicine, Tokushima, Japan.
Kirima
Kazuyoshi
K
Tsuchiya
Koichiro
K
Okamoto
Masumi
M
Hasegawa
Toyoshi
T
Houchi
Hitoshi
H
Yoshizumi
Masanori
M
Tamaki
Toshiaki
T
D000983:Antipyrine / Q000031:analogs & derivatives* / Q000737:chemistry*; D003497:Cyclic N-Oxides / Q000737:chemistry; D000077553:Edaravone; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry*; D010084:Oxidation-Reduction; D019097:Spin Trapping
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D000077553:Edaravone; D000983:Antipyrine