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Br J Pharmacol. 2018 Dec;175(24):4464-4479. doi: 10.1111/bph.14501. Epub 2018 Oct 29.

Alcohol binge disrupts the rat intestinal barrier: the partial protective role of oleoylethanolamide.

Author information

1
Department of Psychobiology and Behavioral Science Methods, Faculty of Psychology, Complutense University, Madrid (UCM), and Red de Trastornos Adictivos (RTA) Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
2
Department of Medicine Microbiology, Faculty of Medicine, UCM, Madrid, Spain.
3
Department of Pharmacology and Toxicology, Faculty of Medicine, UCM, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Imas12 and IUINQ, Madrid, Spain.

Abstract

BACKGROUND AND PURPOSE:

Chronic alcohol consumption alters the gut-brain axis, but little is known about alcohol binge episodes on the functioning of the intestinal barrier. We investigated the influence of ethanol binges on bacterial translocation, gut inflammation and immunity, and tight junction (TJ) structure and the ability of the biolipid oleoylethanolamide (OEA) to prevent ethanol binge-induced intestinal barrier dysfunction.

EXPERIMENTAL APPROACH:

OEA was injected i.p. before repeated ethanol administration by oral gavage. Plasma, spleen, liver and mesenteric lymph nodes (MLN) were collected in sterile conditions for determination of bacterial load. Immune/inflammatory parameters, TJ proteins and apoptotic markers were determined in colonic tissue by RT-PCR and Western blotting. TJ ultrastructure was examined by transmission electron microscopy.

KEY RESULTS:

Ethanol binges induced bacterial translocation to the MLN (mainly) and spleen. Colonic tissues showed signs of inflammation, and activation of innate (Toll-like receptor-4) and adaptive (IgA) immune systems and TJ proteins (occludin and claudin-3) were decreased after ethanol binges. Pretreatment with OEA reduced intestinal inflammation and immune activation and partially preserved the TJ structure affected by alcohol binges but had no effect on alcohol-induced apoptosis. Ultrastructural analyses of colonic TJs revealed dilated TJs in all ethanol groups, with less electron-dense material in non-pretreated rats. The protective effects of i.p. OEA did not reduce bacterial translocation to the MLN. However, intragastric OEA administration significantly reduced plasma LPS levels and bacterial translocation to the MLN.

CONCLUSION AND IMPLICATIONS:

OEA-based pharmacotherapies could potentially be useful to treat disorders characterized by intestinal barrier dysfunction, including alcohol abuse.

PMID:
30248186
PMCID:
PMC6255955
[Available on 2019-12-01]
DOI:
10.1111/bph.14501

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