Cytotoxic effect of As(III) in Caco-2 cells and evaluation of its human intestinal permeability.
Inorganic arsenic has been classified as a carcinogen for humans (Group I). However, its transit across the human intestinal epithelium has not been characterized. Using Caco-2 cells, the thiol-redox balance and apparent permeability coefficients (P(app)) for As(III) in the apical to basolateral (AP-BL) and basolateral to apical (BL-AP) direction were evaluated. After As(III) exposure, GSH-induced synthesis was observed, increasing the GSH/GSSG ratio by elevating the As(III) concentration. The AP-BL permeabilities decreased as the As(III) concentrations increased, indicating the existence of a mediated transport mechanism. The (BL-AP)/(AP-BL) permeability ratios were higher than unity, suggesting the existence of a secretion process.
Institute of Agrochemistry and Food Technology (CSIC), Apdo 73, 46100 Burjassot (Valencia), Spain. mlaparra@iata.csic.es
José Moisés
JM
Laparra
Dinoraz
D
Vélez
Reyes
R
Barberá
Luis
L
Granero
Ana
A
Polache
Rosa
R
Montoro
Rosaura
R
Farré
D001151:Arsenic / Q000493:pharmacokinetics* / Q000633:toxicity*; D018938:Caco-2 Cells; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects; D010084:Oxidation-Reduction; D010539:Permeability
D005978:Glutathione; D001151:Arsenic; D019803:Glutathione Disulfide