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
Nutrition
Caco-2
Cadmium
IEC-18
Tight junction
Cadmium chloride
Macrogol 4000
Annitol
Occludin
Uvomorulin
Animal tissue
Apical membrane
Cell junction
Cell viability
Cellular distribution
Cytotoxicity
Electric resistance
Human
Human tissue
Intestine mucosa permeability
Long term exposure
Molecular size
Nonhuman
Tight junction
Transcytosis
Animals
Caco-2 Cells
Cadherins
Cadmium Chloride
Cadmium Radioisotopes
Cell Membrane Permeability
Cell Survival
Cells, Cultured
Epithelial Cells
Humans
Ileum
Intestinal Absorption
Mannitol
Membrane Proteins
Phosphoproteins
Polyethylene Glycols
Rats
Tight Junctions
Animalia
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