Protective Effects of Free Radical Scavenger Edaravone Against Xanthine Oxidase–Mediated Permeability Increases in Human Intestinal Epithelial Cell Monolayer


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Abstract

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.

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