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has been cited by the following article:

• TITLE: The effect of edaravone to leukocyte rolling and adhesion molecule expression in microvessels

  AUTHORS: Kumi Sakamoto, Tsutomu Yamashita, Hiroshi Yamanishi, Junichiro Yamamoto

  KEYWORDS: Edaravone; Radical; Scavenger; Atherosclerosis; P-Selectin; E-Selectin; ICAM-1

  JOURNAL NAME: Health, Vol.5 No.3, March 7, 2013

  ABSTRACT: Background: Recently, it has become apparent that reactive oxygen species (ROS) play a critical role in the initiation of atherosclerosis. In this study, the effect of radical scavenger edaravone to the leukocyte rolling and to the expression of adhesion molecules on microvascular endothelium was investigated. Methods: DSS induced rat colitis model was used as an inflammation model. Edaravone (10.5 mg/kg, Mitsubishi Tanabe Pharma Corporation, Japan) was used to examine the action of ROS. Images of leukocyte rolling in mesenteric microvessels were investigated in a fluorescence bio-imaging model. Each cross section from the target blood vessel (aotic root, aorta, superior mesenteric artery) were examined by immune-peroxidase staining with anti-P-selectin, E-selectin, ICAM-1 antibody using the streptavidin/biotinylated horseradish peroxidase method. Results: 1) Leukocyte rolling in mesenteric microvessels was significantly increased in colitis. The number of rolling leukocyte was significantly decreased in edaravone group than placebo group (501.3 ± 39.2 vs 252.2 ± 37.2 count/100 μm/10 min). 2) The expression of P-selectin in endothelial cell was significantly increased in colitis. However, this expression was decreased in edaravone group. 3) The expression of E-selectin was not induced to intact aortic root and aorta. In the superior mesenteric artery, the expression was induced by inflammation, and it was attenuated by edaravone. 4) There was little expression of ICAM-1 in both intact aortic root and aortas. While, in the superior mesenteric artery, the expression was confirmed only in placebo group in colitis, and it was attenuated in edaravone group. Conclusions: It was suggested that administration of edaravone led to improving a haemostasis of microcirculation based on down-regulation of adhesion molecules. These results support the evidence that ROS plays a critical role in micro- vascular dysfunction.