Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model.

<h4>Background & aims</h4>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 generati...

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Autores principales: Elhaseen Elamin, Ad Masclee, Kati Juuti-Uusitalo, Sven van Ijzendoorn, Freddy Troost, Harm-Jan Pieters, Jan Dekker, Daisy Jonkers
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/dbfaadaf204848309a5706096b30c17e
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spelling oai:doaj.org-article:dbfaadaf204848309a5706096b30c17e2021-11-18T07:52:59ZFatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model.1932-620310.1371/journal.pone.0058561https://doaj.org/article/dbfaadaf204848309a5706096b30c17e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23526996/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background & aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>These findings show that FAEEs can induce intestinal barrier dysfunction by disrupting the tight junctions, most likely via reactive oxygen species-dependent mechanism.Elhaseen ElaminAd MascleeKati Juuti-UusitaloSven van IjzendoornFreddy TroostHarm-Jan PietersJan DekkerDaisy JonkersPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58561 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Elhaseen Elamin
Ad Masclee
Kati Juuti-Uusitalo
Sven van Ijzendoorn
Freddy Troost
Harm-Jan Pieters
Jan Dekker
Daisy Jonkers
Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model.
description <h4>Background & aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>These findings show that FAEEs can induce intestinal barrier dysfunction by disrupting the tight junctions, most likely via reactive oxygen species-dependent mechanism.
format article
author Elhaseen Elamin
Ad Masclee
Kati Juuti-Uusitalo
Sven van Ijzendoorn
Freddy Troost
Harm-Jan Pieters
Jan Dekker
Daisy Jonkers
author_facet Elhaseen Elamin
Ad Masclee
Kati Juuti-Uusitalo
Sven van Ijzendoorn
Freddy Troost
Harm-Jan Pieters
Jan Dekker
Daisy Jonkers
author_sort Elhaseen Elamin
title Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model.
title_short Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model.
title_full Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model.
title_fullStr Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model.
title_full_unstemmed Fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model.
title_sort fatty acid ethyl esters induce intestinal epithelial barrier dysfunction via a reactive oxygen species-dependent mechanism in a three-dimensional cell culture model.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/dbfaadaf204848309a5706096b30c17e
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