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Title: Protective effects of nonionic tri-block copolymers on bile acid-mediated epithelial barrier disruption.

Translocation of bacteria and other luminal factors from the intestine following surgical injury can be a major driver of critical illness. Bile acids have been shown to play a key role in the loss of intestinal epithelial barrier function during states of host stress. Experiments to study the ability of nonionic block copolymers to abrogate barrier failure in response to bile acid exposure are described. In vitro experiments were performed with the bile salt sodium deoxycholate on Caco-2 enterocyte monolayers using transepithelial electrical resistance to assay barrier function. A bisphenol A coupled triblock polyethylene glycol (PEG), PEG 15-20, was shown to prevent sodium deoxycholate-induced barrier failure. Enzyme-linked immunosorbent assay, lactate dehydrogenase, and caspase 3-based cell death detection assays demonstrated that bile acid-induced apoptosis and necrosis were prevented with PEG 15-20. Immunofluorescence microscopic visualization of the tight junctional protein zonula occludens 1 (ZO-1) demonstrated that PEG 15-20 prevented significant changes in tight junction organization induced by bile acid exposure. Preliminary transepithelial electrical resistance-based studies examining structure-function correlates of polymer protection against bile acid damage were performed with a small library of PEG-based copolymers. Polymer properties associated with optimal protection against bile acid-induced barrier disruption were PEG-based compounds with a molecular weightmore » greater than 10 kd and amphiphilicity. The data demonstrate that PEG-based copolymer architecture is an important determinant that confers protection against bile acid injury of intestinal epithelia.« less
Authors:
; ; ; ; ; ; ; ;  [1] ;  [2]
  1. (Materials Science Division)
  2. (
Publication Date:
OSTI Identifier:
1030901
Report Number(s):
ANL-MSD/JA-70471
Journal ID: ISSN 1073-2322; TRN: US201124%%527
DOE Contract Number:
DE-AC02-06CH11357
Resource Type:
Journal Article
Resource Relation:
Journal Name: Shock; Journal Volume: 36; Journal Issue: 5
Research Org:
Argonne National Laboratory (ANL)
Sponsoring Org:
SC; NIH; Univ. of Chicago Summer Research Program
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; APOPTOSIS; ARCHITECTURE; BACTERIA; BILE; BILE ACIDS; COPOLYMERS; DEATH; DETECTION; ELECTRIC CONDUCTIVITY; IN VITRO; INTESTINES; LACTATE DEHYDROGENASE; MOLECULAR WEIGHT; NECROSIS; PHENOBARBITAL; POLYETHYLENE GLYCOLS; POLYMERS; PROTEINS; SODIUM; TRANSLOCATION