title: Protective effect of edaravone against hypoxia-reoxygenation injury in rabbit cardiomyocytes.
abstract: 1 We examined whether edaravone (Eda), a clinically available radical scavenger, directly protects cardiomyocytes from ischemia/reperfusion (I/R) injury, and whether the timing of its application is critical for protection. 2 Cardioprotective effects of edaravone were tested in the modified cell-pelleting model of ischemia and under exogenous oxidative stress (hydrogen peroxide: H2O2) in isolated adult rabbit ventricular cells. Cell death and reactive oxygen species (ROS) generation were detected using propidium iodide (PI) and DCFH-DA, respectively. These parameters were evaluated objectively using flow cytometory. 3 Hypoxia and reoxygenation aggravated the proportion of dead cells from 32.2+/-1.8% (Baseline) to 51.3+/-2.7% (Control). When 15 microm edaravone was applied either throughout the entire experiment (Through) or only at reoxygenation (Reox), cell death was significantly reduced to 39.9+/-1.8% (P<0.01 vs Control) and 43.3+/-2.5% (P<0.05 vs Control), respectively. In contrast, when edaravone was applied 10 min after reoxygenation, its protective effect disappeared. Cardioprotection by edaravone was more remarkable than that afforded by other free radical scavengers, such as ascorbate and superoxide dismutase (SOD). There is a positive correlation between the cardioprotective effect of edaravone and the extent of ROS reduction. 4 Edaravone blunted the H2O2-induced changes in electrical properties, and significantly prolonged the time to contracture induced by H2O2 in single ventricular myocytes. 5 Taken together, edaravone directly protects cardiomyocytes from I/R injury by attenuating ROS production, even when applied at the time of reoxygenation, suggesting that edaravone could be a potent cardioprotective therapeutic agent against hypoxia-reoxygenation injury.
authors.affiliation: Department of Cardiovascular Medicine, Tottori University Faculty of Medicine, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamawaki
authors.forename: Norihito
authors.initials: N
authors.lastname: Sasaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Shimoyama
authors.forename: Junichiro
authors.initials: J
authors.lastname: Miake
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Ogino
authors.forename: Osamu
authors.initials: O
authors.lastname: Igawa
authors.forename: Fumito
authors.initials: F
authors.lastname: Tajima
authors.forename: Chiaki
authors.initials: C
authors.lastname: Shigemasa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hisatome
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D000077553:Edaravone; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000077553:Edaravone; D010100:Oxygen; D000983:Antipyrine