RT Journal Article
SR Electronic
T1 The Free Radical Scavenger Edaravone Rescues Rats from Cerebral Infarction by Attenuating the Release of High-Mobility Group Box-1 in Neuronal Cells
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 865
OP 874
DO 10.1124/jpet.108.149484
VO 329
IS 3
A1 Kiyoshi Kikuchi
A1 Ko-ichi Kawahara
A1 Salunya Tancharoen
A1 Fumiyo Matsuda
A1 Yoko Morimoto
A1 Takashi Ito
A1 Kamal Krishna Biswas
A1 Kazunori Takenouchi
A1 Naoki Miura
A1 Yoko Oyama
A1 Yuko Nawa
A1 Noboru Arimura
A1 Masahiro Iwata
A1 Yutaka Tajima
A1 Terukazu Kuramoto
A1 Kenji Nakayama
A1 Minoru Shigemori
A1 Yoshihiro Yoshida
A1 Teruto Hashiguchi
A1 Ikuro Maruyama
YR 2009
UL http://jpet.aspetjournals.org/content/329/3/865.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics