Edaravone, a radical scavenger, inhibits mitochondrial permeability transition pore in rat brain.
Edaravone, a radical scavenger, prevents ischemia/reperfusion injury in the brain, but the detailed mechanism is not known. This study examines the effect of edaravone on mitochondrial permeability transition pore (PTP) in rat brain. Edaravone at 10 - 100 microM inhibited Ca(2+)- and H(2)O(2)-induced swelling of mitochondria isolated from rat brain. Addition of Ca(2+) generated reactive oxygen species (ROS) in isolated mitochondria. Edaravone (10 - 100 microM) inhibited Ca(2+)-induced generation of ROS. These results suggest that edaravone inhibits opening of mitochondrial PTP in the brain, and they imply that inhibition of mitochondrial PTP may account for the neuroprotective effect of edaravone.
Takayasu
Yuko
Y
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Nakaki
Junko
J
Kawasaki
Toshiyuki
T
Koda
Ken
K
Ago
Yukio
Y
Baba
Akemichi
A
Matsuda
Toshio
T
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
D016166:Free Radical Scavengers; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D000077553:Edaravone; D002118:Calcium; D000983:Antipyrine