Protective effects of free radical scavenger edaravone against xanthine oxidase-mediated permeability increases in human intestinal epithelial cell monolayer.
The barrier function of the intestinal mucosa can be disturbed under a variety of pathologic insults. Reactive oxygen species play an important role in intestinal mucosal injury. This in vitro study examines the hypothesis that a free radical scavenger, edaravone (ED), ameliorates gut epithelial permeability increase caused by xanthine oxidase (XO)-mediated oxidative stress in a cell monolayer model. Human intestinal epithelial (HIE) cells were grown as monolayer in bicameral chambers. Twenty milliunits per milliliter of XO+0.25 mM of xanthine (XO+X group) or saline (control) were administered into the basal chambers. Another set of chambers was treated with XO+X and 0.6 mg/ml of ED (XO+X+ED group). The permeability was assessed by quantifying the transepithelial passage of fluorescence in isothiocyanate-labeled dextran. In another series of experiments, Escherichia coli C-25 was also applied in an apical chamber to evaluate the bacterial translocation through the monolayer. The concentration of the fluorescence in isothiocyanate-labeled dextran in the basal chamber of the control group was significantly higher than the control (705 +/- 50.2 vs 155 +/- 45.4 mg/dl, P < .01). Treatment with ED prevented this permeability increase induced by the oxidative stress (P < .01). The incidence of bacterial translocation through the HIE monolayer in XO+X group was also higher than that of the control group (75 vs 13%, P < .05). Increased HIE cell monolayer permeability mediated by xanthine and XO was significantly attenuated with ED. This synthesized radical scavenger may have potential clinical applications against gut mucosal barrier dysfunction.
Mukojima
Ken
K
Department of Emergency and Critical Care Medicine, Tokyo Medical University, Tokyo, Japan.
Mishima
Shiro
S
Oda
Jun
J
Homma
Hiroshi
H
Sasaki
Hirokazu
H
Ohta
Shoichi
S
Yukioka
Tetsuo
T
D000328:Adult; D000704:Analysis of Variance; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018988:Bacterial Translocation / Q000187:drug effects; D016009:Chi-Square Distribution; D000077553:Edaravone; D004847:Epithelial Cells / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability; D014969:Xanthine Oxidase / Q000494:pharmacology*
D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D000077553:Edaravone; D000983:Antipyrine