Clarification of the Mechanism of Structural Change Induced by Reoxygenation following the Induction of Lipid Peroxidation in Caco-2 Cell Monolayers

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Author(s)

    • TOMITA Mikio
    • Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Science
    • NAGIRA Mayuko
    • Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Science University of Tokyo
    • HAGA Makoto
    • Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Science University of Tokyo
    • HAYASHI Masahiro
    • Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Science

Abstract

  Recently, we established a system for assessing ischemia/reperfusion injury, specifically the opening of tight junctions (TJ), caused by reoxygenation following the induction of lipid peroxidation by <i>tertiary</i>-butylhydroperoxide (<i>t</i>-BuOOH), using the human intestinal epithelial cell line Caco-2 in order to focus on the barrier function of the epithelium independent of the vascular compartment. In the present study, we attempted to identify factors involved in the structural changes induced by reoxygenation using 0.5 mM <i>t</i>-BuOOH in Caco-2 cell monolayers. Glutathione (GSH) and N-acetylcystein, a precursor of GSH, inhibited the opening of TJ evoked by reoxygenation following the induction of lipid peroxidation by 0.5 mM of <i>t</i>-BuOOH. Tiron, as a cell permeable superoxide anion scavenger and deferoxamine, an iron-chelating agent ameliorated the opening in a dose-dependent manner. Also, Tiron suppressed the apical-to-basal and basal-to-apical permeability of the increased Rhodamine123 by reoxygenation in a concentration-dependent manner. These results collectively suggest that superoxide anion and iron ions play an important role or contribute to structural changes such as the opening of TJ induced by reoxygenation following the induction of lipid peroxidation by 0.5 mM <i>t</i>-BuOOH.<br>

Journal

  • Drug Metabolism and Pharmacokinetics

    Drug Metabolism and Pharmacokinetics 17(1), 83-91, 2002-03-29

    The Japanese Society for the Study of Xenobiotics

References:  42

Cited by:  4

Codes

  • NII Article ID (NAID)
    10008198173
  • NII NACSIS-CAT ID (NCID)
    AA1162652X
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    09161139
  • Data Source
    CJP  CJPref  J-STAGE 
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