Kiyoshi KikuchiKo Ichi KawaharaSalunya TancharoenFumiyo MatsudaYoko MorimotoTakashi ItoKamal Krishna BiswasKazunori TakenouchiNaoki MiuraYoko OyamaYuko NawaNoboru ArimuraMasahiro IwataYutaka TajimaTerukazu KuramotoKenji NakayamaMinoru ShigemoriYoshihiro YoshidaTeruto HashiguchiIkuro MaruyamaKagoshima University Faculty of MedicineMahidol UniversityKagoshima UniversityOmuta City General HospitalKurume University2018-09-132018-09-132009-06-01Journal of Pharmacology and Experimental Therapeutics. Vol.329, No.3 (2009), 865-87415210103002235652-s2.0-66749132080https://repository.li.mahidol.ac.th/handle/123456789/27216Edaravone, a potent free radical scavenger, is clinically used for the treatment of cerebral infarction in Japan. Here, we examined the effects of edaravone on the dynamics of high-mobility group box-1 (HMGB1), which is a key mediator of ischemic-induced brain damage, during a 48-h postischemia/ reperfusion period in rats and in oxygen-glucose-deprived (OGD) PC12 cells. HMGB1 immunoreactivity was observed in both the cytoplasm and the periphery of cells in the cerebral infarction area 2 h after reperfusion. Intravenous administration of 3 and 6 mg/kg edaravone significantly inhibited nuclear translocation and HMGB1 release in the penumbra area and caused a 26.5 ± 10.4 and 43.8 ± 0.5% reduction, respectively, of the total infarct area at 24 h after reperfusion. Moreover, edaravone also decreased plasma HMGB1 levels. In vitro, edaravone dose-dependently (1-10 μM) suppressed OGD- and H2O2-induced HMGB1 release in PC12 cells. Furthermore, edaravone (3-30 μM) blocked HMGB1-triggered apoptosis in PC12 cells. Our findings suggest a novel neuroprotective mechanism for edaravone that abrogates the release of HMGB1. Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1124/jpet.108.149484