Biphasic effect of iron on human intestinal Caco-2 cells: early effect on tight junction permeability with delayed onset of oxidative cytotoxic damage

S Ferruzza, M L Scarino, Lorraine Gambling, F Natella, Y Sambuy

    Research output: Contribution to journalArticle

    29 Citations (Scopus)

    Abstract

    Treatment of differentiated human intestinal Caco-2 cells with Fe(II) ascorbate altered tight junction permeability in a dose and time-dependent way for up to 3 hr of treatment Upon iron removal and transfer to complete culture medium, the effect was reversible up to 10 microM Fe(II), while at higher concentrations a late phase toxic effect was observed. Reduction of intracellular energy abolished the short term effect of iron on tight junction permeability without affecting its cellular uptake, suggesting that active processes, other than transport, were involved. The short term effect of iron the permeability of tight junctions did not appear to result from the generation of reactive oxygen species, as it was not prevented by antioxidant treatment under normal energy conditions. Conversely, the late phase effect leading to both apoptosis and necrosis during the 24 hr following iron removal could be reduced by antioxidant treatment and was exacebated by GSH depletion. Iron induced oxidative stress may therefore be responsible for membrane damage and cellular death occurring in the late phase. The reported effects of iron on intestinal tight junction permeability followed by more widespread cytotoxicity from oxidative events should be considered in light of the extensive use of iron supplementation in different phases of human life.
    Original languageEnglish
    Pages (from-to)89-99
    Number of pages11
    JournalCellular and Molecular Biology
    Volume49
    Issue number1
    Publication statusPublished - 1 Feb 2003

    Fingerprint

    Caco-2 Cells
    Tight Junctions
    Permeability
    Iron
    Antioxidants
    Oxidative stress
    Poisons
    Cytotoxicity
    Culture Media
    Reactive Oxygen Species
    Apoptosis
    Membranes
    Oxidative Stress
    Necrosis

    Keywords

    • Caco-2 Cells
    • Electric Impedance
    • Humans
    • Intestines
    • Iron
    • Oxidative Stress
    • Permeability
    • Tight Junctions
    • Time Factors

    Cite this

    Biphasic effect of iron on human intestinal Caco-2 cells: early effect on tight junction permeability with delayed onset of oxidative cytotoxic damage. / Ferruzza, S; Scarino, M L; Gambling, Lorraine; Natella, F; Sambuy, Y.

    In: Cellular and Molecular Biology, Vol. 49, No. 1, 01.02.2003, p. 89-99.

    Research output: Contribution to journalArticle

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