Effects of cadmium chloride on the paracellular barrier function of intestinal epithelial cell lines
article
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.
Topics
Caco-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
TNO Identifier
234968
ISSN
0041008X
Source
Toxicology and Applied Pharmacology, 155(2), pp. 117-126.
Pages
117-126
Files
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