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

• Published in: DRUG METABOLISM AND PHARMACOKINETICS Vol. 17; no. 1; pp. 83 - 91
• Main Authors: Tomita, Mikio, Nagira, Mayuko, Haga, Makoto, Hayashi, Masahiro
• Format: Journal Article
• Language: English; Japanese
• Published: England Elsevier Ltd 2002; Japanese Society for the Study of Xenobiotics
• Subjects: Caco-2 cell monolayers; iron ions; ischemia; lipid peroxidation; P-glycoprotein; reperfusion injury; superoxide anion; TJ opening; P-glycoprotein; Caco-2 cell monolayers; TJ opening; iron ions; reperfusion injury; superoxide anion; lipid peroxidation; ischemia
• ISSN: 1347-4367; 1880-0920
• DOI: 10.2133/dmpk.17.83

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 tertiary-butylhydroperoxide (t-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 t-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 t-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 t-BuOOH.