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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|
Ko Ichi Kawahara
Kamal Krishna Biswas
Kagoshima University Faculty of Medicine
Omuta City General Hospital
|Keywords:||Biochemistry, Genetics and Molecular Biology;Pharmacology, Toxicology and Pharmaceutics|
|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.|
|Appears in Collections:||Scopus 2006-2010|
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