Transport of methylated thioarsenates in an in-vitro intestinal model
Franziska Geist (07/2014-10/2015)
Support: Britta Planer-Friedrich, Sinikka Hinrichsen
Gut microbiota produce methylated thioarsenates after exposure to arsenic. The extent to which these compounds are intestinally absorbed is largely unknown. The aim of this thesis was to estimate the cellular retention and the intestinal transport of monomethylmonothioarsenate, dimethylmonothioarsenate, monomethylarsenate, and dimethylarsenate by means of an in vitro model of the small intestine with human Caco-2 cells. The apical side was treated with 2.7 µM of the respective arsenic compound. After 2, 4, 6, and 8 h the intracellular and basal total arsenic concentrations were quantified by ICP-MS. The importance of phosphate transporters was investigated by phosphate-free transport experiments. Due to disruptions of the cell monolayers, the importance of the paracellular way could not be estimated. Only after the treatment with dimethylmonothioarsenate, a marked intracellular arsenic retention was detected (2.8 ± 0.2 % As/106 cells after 8 h). Arsenic transport through the cell monolayer was also the highest (7.3 ± 1.5 % As/106 cells after 8 h; apparent permeability coefficient (Papp) 0.65 ± 0.10·10-6 cm/s). The arsenic transport was lower for the treatments with the other three compounds (0.7 – 2.7 % As/106 cells after 8 h; Papp 0.11·10-6 - 0.13·10-6 cm/s). The results of phosphate-free experiments indicate that apical phosphate transporters are important for the absorption of dimethylmonothioarsenate and to a lesser extent also for that of monomethylmonothioarsenate. Considering the presystemic formation of dimethylmonothioarsenate by thiolation of dimethylarsenate, its high toxicity and its significant intestinal absorption, dimethylmonothioarsenate has to be considered as a species of high toxic concern for the human body.