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
Nutrition
Lactate dehydrogenase
Palmitoylcarnitine
Propidium iodide
Apical membrane
Cell membrane
Cell strain caco 2
Cell viability
Controlled study
Drug absorption
Drug cytotoxicity
Drug transport
Electric resistance
Human
Human cell
Image processing
Intestine absorption
Macromolecule
Oral drug administration
Priority journal
Protein localization
Tight junction
Animals
Biological Transport
Caco-2 Cells
Cell Survival
Dose-Response Relationship, Drug
Egtazic Acid
Electric Impedance
Humans
Immunohistochemistry
Intestinal Absorption
Membrane Proteins
Octoxynol
Palmitoylcarnitine
Phosphoproteins
Rats
Tight Junctions
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TNO identifier
234728
ISSN
0022-3565
Source
Journal of Pharmacology and Experimental Therapeutics, 287 (1), 395-402
Document type
article