Estimation of the human intestinal permeability of butyltin species using the Caco-2 cell line model.
The main objective of the work was the setup of the Caco-2 human intestinal cell-line model for the study of the intestinal permeation of monobutyltin (MBT), dibutyltin (DBT) and tributyltin (TBT). The study was focused in gathering information on (a) the relative permeability of butyltins, (b) their possible permeation routes (paracellular/transcellular) and (c) the eventual interactions between the different butyltins when occurring as a mixture. The presence of basolateral serum protein greatly influenced the permeability, causing a large net clearance, but the apparent permeability (Papp) values were comparable to that of phenolred, suggesting a low in vivo permeability of the butyltins. The found permeability pattern correlates well with the general in vivo toxicity pattern (trialkyltin>dialkyltin>>monoalkyltin). The accumulation pattern (DBT>TBT>MBT) was different from that of permeability and may be an important element regarding the elucidation of some specific strong toxic effects caused by the dialkyltins in several species. The transport of MBT and DBT was found to be dependent on the paracellular route status. An interaction between the butyltin compounds in a mixture was found for the accumulation results (the accumulation was significantly higher for the three compounds when in a mixture). A set of useful information about the butyltin accumulation and transport by the epithelial Caco-2 cell line was, thus, achieved, constituting a starting point for future research on the permeability of butyltins from contaminated food and beverages.
Azenha
M A
MA
CIQ and Department of Chemistry, Faculty of Science, University of Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal. mazenha@fc.up.pt
Evangelista
R
R
Martel
F
F
Vasconcelos
M T
MT
D001692:Biological Transport; D018938:Caco-2 Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004785:Environmental Pollutants / Q000378:metabolism* / Q000494:pharmacology; D005506:Food Contamination / Q000032:analysis; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009947:Organotin Compounds / Q000378:metabolism* / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism; D010539:Permeability; D013329:Structure-Activity Relationship
D004338:Drug Combinations; D004785:Environmental Pollutants; D009947:Organotin Compounds; D010088:Oxidoreductases