Print Email Facebook Twitter Absorption enhancement, structural changes in tight junctions and cytotoxicity caused by palmitoyl carnitine in Caco-2 and IEC-18 cells Title Absorption enhancement, structural changes in tight junctions and cytotoxicity caused by palmitoyl carnitine in Caco-2 and IEC-18 cells Author Duizer, E. van der Wulp, C. Versantvoort, C.H.M. Groten, J.P. Centraal Instituut voor Voedingsonderzoek TNO Publication year 1998 Abstract Palmitoyl carnitine chloride (PCC) has been shown to be an effective enhancer of intestinal transport of hydrophilic molecules. The exact mechanism by which the epithelial barrier function is decreased is not clear. In an attempt to elucidate the mechanism of action of PCC, we studied the relationship among absorption enhancement, cell viability and tight junction protein localization in the human colonic Caco-2 cell line and the rat small intestinal cell line IEC-18. Filter-grown cells were exposed to 0 to 1 mM PCC for 30 min, and the efficacy of PCC treatment was determined by assessing the transepithelial electrical resistance and the apparent permeability for mannitol and PEG-4000. Membrane lysis and cytotoxicity were assessed by measurement of lactate dehydrogenase leakage and uptake of propidium iodide and neutral red. The immunolocalization of the tight junctional protein ZO-1 was quantified using CSLM and image-processing software. In both cell lines, PCC caused a dose-dependent decrease in transepithelial electrical resistance and a concomitant increase in the permeability for mannitol and PEG-4000. The transport enhancement was accompanied by an increase in apical membrane permeability and a reduction in cell viability. At higher PCC concentrations (≥ 0.4 mM), the distribution of the tight junctional protein ZO-1 was changed and cells were unable to recover viability. PCC is effective as an absorption enhancer for hydrophilic macromolecules. However, lytic effects on the cell membrane and reduced cell viability were concomitant with transport enhancement. Subject NutritionLactate dehydrogenasePalmitoylcarnitinePropidium iodideApical membraneCell membraneCell strain caco 2Cell viabilityControlled studyDrug absorptionDrug cytotoxicityDrug transportElectric resistanceHumanHuman cellImage processingIntestine absorptionMacromoleculeOral drug administrationPriority journalProtein localizationTight junctionAnimalsBiological TransportCaco-2 CellsCell SurvivalDose-Response Relationship, DrugEgtazic AcidElectric ImpedanceHumansImmunohistochemistryIntestinal AbsorptionMembrane ProteinsOctoxynolPalmitoylcarnitinePhosphoproteinsRatsTight Junctions To reference this document use: http://resolver.tudelft.nl/uuid:b7084166-ed4e-4824-a76d-7462c75e45e6 TNO identifier 234728 ISSN 0022-3565 Source Journal of Pharmacology and Experimental Therapeutics, 287 (1), 395-402 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.