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Title: The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells
Authors: Kiyoshi Kikuchi
Ko Ichi Kawahara
Salunya Tancharoen
Fumiyo Matsuda
Yoko Morimoto
Takashi Ito
Kamal Krishna Biswas
Kazunori Takenouchi
Naoki Miura
Yoko Oyama
Yuko Nawa
Noboru Arimura
Masahiro Iwata
Yutaka Tajima
Terukazu Kuramoto
Kenji Nakayama
Minoru Shigemori
Yoshihiro Yoshida
Teruto Hashiguchi
Ikuro Maruyama
Kagoshima University Faculty of Medicine
Mahidol University
Kagoshima University
Omuta City General Hospital
Kurume University
Keywords: Biochemistry, Genetics and Molecular Biology;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jun-2009
Citation: Journal of Pharmacology and Experimental Therapeutics. Vol.329, No.3 (2009), 865-874
Abstract: Edaravone, 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.
ISSN: 15210103
Appears in Collections:Scopus 2006-2010

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