Effects of cadmium chloride on the paracellular barrier function of intestinal epithelial cell lines

In the present study we characterized the functional and structural disrupt ion of the paracellular barrier of intestinal epithelium in vitro in relati on to cytotoxicity after apical Cd2+ exposure. For that purpose filter-grow n Caco-2 and IEC-18 cells were apically exposed to 5 to 100 mu M 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 Cd2in Caco-2 cells after 4 h exposure were a decrease in transepithelial elect rical resistance, increased permeabilities of mannitol and PEG-4000, and ch anges in intercellular localization of ZO-1, occludin, and e-cadherin, The effects were far more pronounced after prolonged exposure. The disruption o f the paracellular barrier by 5 to 30 mu M Cd2+ was detected without a sign ificant loss of viability of the Caco-2 cells. In the IEC-18 cells, Cd2+ co ncentrations affecting the barrier (50 and 100 mu M) also affected cell via bility. In both cell lines the effects on the cell layers continued to deve lop 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 intesti nal epithelial cells is accompanied by tight junction disruption. It is con cluded that Cd2+ causes increased paracellular permeability by disruption o f 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. (C) 1999 Academic Press.