Edaravone directly reacts with singlet oxygen and protects cells from attack

Abstract

Aims Protective effects of edaravone, an approved medicine for acute brain infarction in Japan, on cell death induced by singlet oxygen ( 1O 2) were examined. Main method The 1O 2 scavenging activity was examined by direct analysis of near-infrared luminescence in a cell-free system and by fluorospectrometry in the presence of cells. The protective effects of edaravone on 1O 2-induced cell death were examined, using rat neuronal B50 cells. Cell death was evaluated by mitochondrial respiration (MTT assay), confocal microscopy and time-lapse imaging. The chemical reaction of edaravone with 1O 2 was examined by production analysis using high performance liquid chromatography (HPLC). Key findings When rose Bengal (RB) in D 2O was irradiated by a 514 nm laser beam, the signal of 1O 2 was observed. Edaravone suppressed the 1O 2 signal more potently than azide, a 1O 2 scavenger. When B50 cells were irradiated by 525 nm green light in the RB solution, production of 1O 2 and induction of cell death were observed. The fluorospectrometric study and the MTT assay revealed that 100–400 µM edaravone suppressed the 1O 2 production and attenuated cell death in a concentration-dependent manner. Confocal microscopy and the time-lapse imaging revealed that edaravone prevented the impairment of membrane integrity and the progression of cell death induced by 1O 2. The HPLC study revealed that edaravone chemically reacted with 1O 2 and changed another compound. Significance Since 1O 2 is possibly involved in post-ischemic neuronal damage, the clinically approved curative effects of edaravone on acute brain infarction might be attributed to its potent 1O 2 scavenging activity.