Document Detail

Protective effects of nonionic triblock copolymers on bile acid-mediated epithelial barrier disruption.
MedLine Citation:
PMID:  21937955     Owner:  NLM     Status:  MEDLINE    
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 weight 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.
Adam Edelstein; David Fink; Mark Musch; Vesta Valuckaite; Olga Zaborina; Simonida Grubjesic; Millicent A Firestone; Jeffrey B Matthews; John C Alverdy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  36     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-18     Completed Date:  2012-05-16     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  451-7     Citation Subset:  IM    
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MeSH Terms
Apoptosis / drug effects
Benzhydryl Compounds
Bile Acids and Salts / pharmacology*
Caco-2 Cells
Caspase 3 / metabolism
Deoxycholic Acid / pharmacology
Intestinal Mucosa / drug effects*
Membrane Proteins / metabolism
Microscopy, Fluorescence
Necrosis / chemically induced,  prevention & control
Phenols / chemistry
Phosphoproteins / metabolism
Polyethylene Glycols / chemistry
Polymers / chemistry,  pharmacology*
Zonula Occludens-1 Protein
Grant Support
5R01GM062344-11/GM/NIGMS NIH HHS; DK062719-22/DK/NIDDK NIH HHS; R01 GM062344/GM/NIGMS NIH HHS; R01 GM062344-12/GM/NIGMS NIH HHS
Reg. No./Substance:
0/Benzhydryl Compounds; 0/Bile Acids and Salts; 0/Membrane Proteins; 0/Phenols; 0/Phosphoproteins; 0/Polyethylene Glycols; 0/Polymers; 0/TJP1 protein, human; 0/Zonula Occludens-1 Protein; 005990WHZZ/Deoxycholic Acid; EC 3.4.22.-/Caspase 3; MLT3645I99/bisphenol A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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