title: Protective effects of free radical scavenger edaravone against xanthine oxidase-mediated permeability increases in human intestinal epithelial cell monolayer.
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.
authors.affiliation: Department of Emergency and Critical Care Medicine, Tokyo Medical University, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Mukojima
authors.forename: Shiro
authors.initials: S
authors.lastname: Mishima
authors.forename: Jun
authors.initials: J
authors.lastname: Oda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Homma
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Sasaki
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ohta
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yukioka
mesh_terms: 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*
chemical_list: D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D000077553:Edaravone; D000983:Antipyrine