Abstract
Objective
Effects of potent free radical scavenger, edaravone, on oxidative stress-induced endothelial
damage and early atherosclerosis were investigated using animal models and cultured
cells.
Methods and results
Endothelial apoptosis was induced by 5-min intra-arterial exposure of a rat carotid
artery with 0.01 mmol/L H2O2. Edaravone treatment (10 mg/kg i.p.) for 3 days suppressed endothelial apoptosis, as evaluated by chromatin
staining of en face specimens at 24 h, by approximately 40%. Similarly, edaravone dose-dependently inhibited H2O2-induce apoptosis of cultured endothelial cells in parallel with the inhibition of
8-isoprostane formation, 4-hydroxy-2-nonenal (4-HNE) accumulation and VCAM-1 expression.
Next, apolipoprotein-E knockout mice were fed a high-cholesterol diet for 4 weeks
with edaravone (10 mg/kg i.p.) or vehicle treatment. Edaravone treatment decreased atherosclerotic lesions
in the aortic sinus (0.18 ± 0.01 to 0.09 ± 0.01 mm2, P < 0.001) and descending aorta (5.09 ± 0.86 to 1.75 ± 0.41 mm2, P < 0.05), as evaluated by oil red O staining without influence on plasma lipid concentrations
or blood pressure. Dihydroethidium labeling and cytochrome c reduction assay showed that superoxide anions in the aorta were suppressed by edaravone.
Also, plasma 8-isoprostane concentrations and aortic nitrotyrosine, 4-HNE and VCAM-1
contents were decreased by edaravone treatment.
Conclusions
These results suggest that edaravone may be a useful therapeutic tool for early atherosclerosis,
pending the clinical efficacy.
Keywords
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Article info
Publication history
Published online: June 28, 2006
Accepted:
May 19,
2006
Received in revised form:
May 9,
2006
Received:
November 28,
2005
Identification
Copyright
© 2006 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
