The role of edaravone on the impairment of endothelial barrier function induced by acute oxidative stress in cultured human umbilical vein endothelial cell monolayer.
BACKGROUND
The aim was to determine the effects of a novel free radical scavenger, edaravone, 3-methyl-1-phenyl-2-pyrazoline-5-one (ED), against endothelial barrier dysfunction induced by acute oxidative stress in cultured human umbilical vein endothelial cells (HUVECs).


METHODS
To estimate the integrity of the HUVEC monolayer, transendothelial electrical resistance (TEER) was measured for 3 hours. We investigated the permeability change of the monolayer by measuring the concentration of fluorescence in isothiocyanate-labeled dextran (FITC-Dx), and estimated the degree of oxidative stress in terms of hydrogen peroxide (H2O2) in the apical chambers.


RESULTS
The TEER changes in both xanthine oxidase (XO)+xanthine (X) and X/XO+ED group were significantly lower than the control group (p < 0.001). The amount of 4 FITC-Dx in the XO+X group was significantly higher than the control group at 3 hours (p < 0.001). In the XO+X group, the concentration of H2O2 was significantly higher than control and the X/XO+ED group (p < 0.001 each). Thus, edaravone improved the disturbed endothelial barrier function induced by acute oxidative stress.


CONCLUSIONS
The permeability increase induced by acute oxidative stress was prevented by free radical scavenger edaravone significantly in vitro. This radical scavenger may have clinical applications to protect against endothelial barrier dysfunction.
Morozumi
J
J
Osaka Prefectural Senshu Critical Care Medical Center, Osaka, Japan. j-moro@par.odn.ne.jp
Mishima
S
S
Ohta
S
S
Fujikawa
T
T
Sasaki
H
H
Noda
M
M
Yukioka
T
T
D000704:Analysis of Variance; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D000077553:Edaravone; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000648:ultrastructure; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D014471:Umbilical Veins
D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide; D000077553:Edaravone; D000983:Antipyrine