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Characterization of the intestinal absorption of arsenate, monomethylarsonic acid, and dimethylarsinic acid using the caco-2 cell line

Abstract:

Many toxicological studies have been conducted with arsenic species in target organ cell lines. However, although epithelial gastrointestinal cells constitute the first barrier to the absorption of contaminants, studies using intestinal cells are scarce. The present study examines absorption through the intestinal epithelium of the pentavalent arsenic species most commonly found in foods [arsenate, As(V); monomethylarsonic acid, MMA(V); and dimethylarsinic acid, DMA(V)], using the Caco-2 cell line as a model. Different concentrations (1.3-667.6 μ M) and culture conditions (media, pH, addition of phosphates, and treatment with ethylenediaminetetraacetic acid) were evaluated to characterize such transport. The apparent permeabilities indicate that the methylated species show low absorption, whereas As(V) is a compound with moderate absorption. The kinetic study shows only a saturable component for MMA(V) transport in the range of concentrations assayed. The existence of paracellular transport was shown for all of the species, with greater significance in the case of the methylated forms. As(V) absorption was inhibited by 10 mM phosphate, and a phosphate transporter therefore could take part in intestinal absorption. Acidification of the medium (pH 5.5) resulted in a marked increase in As(V) and DMA(V) permeability (4-8 times, respectively) but not in MMA(V) permeability. This makes it necessary to consider the possible existence of absorption in the proximal intestine and even in the stomach, where the environment is acidic; alternatively, an H+-dependent transporter may be involved. The results obtained constitute the basis for future research on the mechanisms involved in the intestinal absorption of arsenic and its species, a decisive step in relation to their toxic action. © 2010 American Chemical Society.