Fatty Acid Ethyl Esters Induce Intestinal Epithelial Barrier Dysfunction via a Reactive Oxygen Species-Dependent Mechanism in a Three-Dimensional Cell Culture Model

Elhaseen Elamin, Ad Masclee, Kati Juuti-Uusitalo, Sven van IJzendoorn, Freddy Troost, Harm Jan Pieters, Jan Dekker, Daisy Jonkers

    Research output: Contribution to journalArticleScientificpeer-review

    27 Citations (Scopus)

    Abstract

    <p>Background & Aims: Evidence is accumulating that ethanol and its oxidative metabolite, acetaldehyde, can disrupt intestinal epithelial integrity, an important factor contributing to ethanol-induced liver injury. However, ethanol can also be metabolized non-oxidatively generating phosphatidylethanol and fatty acid ethyl esters (FAEEs). This study aims to investigate the effects of FAEEs on barrier function, and to explore the role of oxidative stress as possible mechanism. Methods: Epithelial permeability was assessed by paracellular flux of fluorescein isothiocyanate-conjugated dextran using live cell imaging. Cell integrity was evaluated by lactate dehydrogenase release. Localization and protein levels of ZO-1 and occludin were analyzed by immunofluorescence and cell-based ELISA, respectively. Intracellular oxidative stress and cellular ATP levels were measured by dichlorofluorescein and luciferase driven bioluminescence, respectively. Results: In vitro, ethyl oleate and ethyl palmitate dose dependently increased permeability associated with disruption and decreased ZO-1 and occludin protein levels, respectively, and increased intracellular oxidative stress without compromising cell viability. These effects could partially be attenuated by pretreatment with the antioxidant, resveratrol, pointing to the role of oxidative stress in the FAEEs-induced intestinal barrier dysfunction. Conclusions: These findings show that FAEEs can induce intestinal barrier dysfunction by disrupting the tight junctions, most likely via reactive oxygen species-dependent mechanism.</p>
    Original languageEnglish
    Article numbere58561
    JournalPLoS ONE
    Volume8
    Issue number3
    DOIs
    Publication statusPublished - 2013
    Publication typeA1 Journal article-refereed

    Keywords

    • 3D cell culture
    • fatty acid ethyl esters
    • phosphatidylethanol

    Publication forum classification

    • Publication forum level 2

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