Print Email Facebook Twitter Effects of cadmium chloride on the paracellular barrier function of intestinal epithelial cell lines Title Effects of cadmium chloride on the paracellular barrier function of intestinal epithelial cell lines Author Duizer, E. Gilde, A.J. Versantvoort, C.H.M. Groten, J.P. Centraal Instituut voor Voedingsonderzoek TNO Publication year 1999 Abstract In the present study we characterized the functional and structural disruption of the paracellular barrier of intestinal epithelium in vitro in relation to cytotoxicity after apical Cd2+ exposure. For that purpose filter-grown Caco-2 and IEC-18 cells were apically exposed to 5 to 100 μM CdCl2 for 4 or 14 h. It was found that the effects of Cd2+ on the epithelial barrier were concentration- and time-dependent. The first detected effects of Cd2+ in Caco-2 cells after 4 h exposure were a decrease in transepithelial electrical resistance, increased permeabilities of mannitol and PEG-4000, and changes in intercellular localization of ZO-1, occludin, and e-cadherin. The effects were far more pronounced after prolonged exposure. The disruption of the paracellular barrier by 5 to 30 μM Cd2+ was detected without a significant loss of viability of the Caco-2 cells. In the IEC-18 cells, Cd2+ concentrations affecting the barrier (50 and 100 μM) also affected cell viability. In both cell lines the effects on the cell layers continued to develop after removal of extracellular Cd2+. This correlated with the cellular retention of Cd2+, which was high for the 12 h following 4 h accumulation. This study showed that the decreased epithelial barrier function of intestinal epithelial cells is accompanied by tight junction disruption. It is concluded that Cd2+ causes increased paracellular permeability by disruption of junctional function and structure. The initial junctional effects of Cd2+ suggest that Cd2+ increases its own bioavailability by causing disruption of the intestinal paracellular barrier. Subject NutritionCaco-2CadmiumIEC-18Tight junctionCadmium chlorideMacrogol 4000AnnitolOccludinUvomorulinAnimal tissueApical membraneCell junctionCell viabilityCellular distributionCytotoxicityElectric resistanceHumanHuman tissueIntestine mucosa permeabilityLong term exposureMolecular sizeNonhumanTight junctionTranscytosisAnimalsCaco-2 CellsCadherinsCadmium ChlorideCadmium RadioisotopesCell Membrane PermeabilityCell SurvivalCells, CulturedEpithelial CellsHumansIleumIntestinal AbsorptionMannitolMembrane ProteinsPhosphoproteinsPolyethylene GlycolsRatsTight JunctionsAnimalia To reference this document use: http://resolver.tudelft.nl/uuid:c20c7597-bf76-4252-906e-5d9b16040c5b DOI https://doi.org/10.1006/taap.1998.8589 TNO identifier 234968 ISSN 0041-008X Source Toxicology and Applied Pharmacology, 155 (2), 117-126 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.