Oleic acid and docosahexaenoic acid cause an increase in the paracellular absorption of hydrophilic compounds in an experimental model of human absorptive enterocytes.
Surface active compounds present in food possibly have the ability to enhance the absorption of water soluble toxic agents. Therefore, we investigated whether fatty acids such as oleic acid and docosahexaenoic acid (DHA), both commonly present in food, negatively affect the integrity of tight junctions (TJ) in the intestinal epithelium and thereby increase the absorption of poorly absorbed hydrophilic substances. Caco-2 cells, which are derived from human absorptive enterocytes, were grown on permeable filters for 20-25 days. Differentiated cell monolayers were apically exposed for 90min to mannitol in emulsions of oleic acid (5, 15 or 30mM) or DHA (5, 15 or 30mM) in an experimental medium with or without Ca(2+) and Mg(2+). Absorption of (14)C-mannitol increased and trans-epithelial electrical resistance (TEER) decreased in cell monolayers exposed to oleic acid and DHA, compared to controls. Cytotoxicity, measured as leakage of LDH, was higher in groups exposed to 30mM oleic acid and all concentrations of DHA. Morphology of the cell monolayers was studied by using fluorescence microscopy. Exposure of cell monolayers to 5mM DHA for 90min resulted in a profound alteration of the cell-cell contacts as detected by staining the cells for beta-catenin. Oleic acid (30mM) treatment also induced dissolution of the cell-cell contacts but the effect was not as pronounced as with DHA. Cell monolayers were also exposed for 180min to 250nM cadmium (Cd) in emulsions of oleic acid (5 or 30mM) or DHA (1 or 5mM), in an experimental medium with Ca(2+) and Mg(2+). Retention of Cd in Caco-2 cells was higher after exposure to 5mM oleic acid but lower after exposure to 30mM oleic acid and DHA. Absorption of Cd through the monolayers increased after DHA exposure but not after exposure to oleic acid. Our results indicate that fatty acids may compromise the integrity of the intestinal epithelium and that certain lipids in food may enhance the paracellular absorption of poorly absorbed hydrophilic substances.
Aspenström-Fagerlund
Bitte
B
Toxicology Division, National Food Administration, P.O. Box 622, SE-75126 Uppsala, Sweden; Department of Pathology, Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Box 7028, SE-75007, Uppsala, Sweden. Electronic address: bfas@slv.se.
Ring
Linda
L
Toxicology Division, National Food Administration, P.O. Box 622, SE-75126 Uppsala, Sweden.
Aspenström
Pontus
P
Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE-75124 Uppsala, Sweden.
Tallkvist
Jonas
J
Department of Pathology, Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Box 7028, SE-75007, Uppsala, Sweden.
Ilbäck
Nils-Gunnar
NG
Toxicology Division, National Food Administration, P.O. Box 622, SE-75126 Uppsala, Sweden; Department of Medical Sciences, Section for Infectious Diseases, Uppsala University, SE-75185 Uppsala, Sweden.
Glynn
Anders W
AW
Toxicology Division, National Food Administration, P.O. Box 622, SE-75126 Uppsala, Sweden; Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-75236 Uppsala, Sweden.
D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D019256:Cadmium Chloride / Q000493:pharmacokinetics; D018929:Cell Culture Techniques; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D017097:Electric Impedance; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism; D005502:Food / Q000592:standards; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D019301:Oleic Acid / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000493:pharmacokinetics*; D019108:Tight Junctions / Q000378:metabolism*
D013501:Surface-Active Agents; D004281:Docosahexaenoic Acids; D019301:Oleic Acid; D019256:Cadmium Chloride