title: Edaravone, a radical scavenger, inhibits mitochondrial permeability transition pore in rat brain.
abstract: 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.
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takayasu
authors.forename: Junko
authors.initials: J
authors.lastname: Nakaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Ken
authors.initials: K
authors.lastname: Koda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ago
authors.forename: Akemichi
authors.initials: A
authors.lastname: Baba
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuda
mesh_terms: 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
chemical_list: 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