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.