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Protective effects of nonionic triblock copolymers on bile acid-mediated epithelial barrier disruption.
- Source :
-
Shock (Augusta, Ga.) [Shock] 2011 Nov; Vol. 36 (5), pp. 451-7. - Publication Year :
- 2011
-
Abstract
- 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.
- Subjects :
- Apoptosis drug effects
Benzhydryl Compounds
Caco-2 Cells
Caspase 3 metabolism
Deoxycholic Acid pharmacology
Humans
Membrane Proteins metabolism
Microscopy, Fluorescence
Necrosis chemically induced
Necrosis prevention & control
Phenols chemistry
Phosphoproteins metabolism
Polyethylene Glycols chemistry
Polymers chemistry
Zonula Occludens-1 Protein
Bile Acids and Salts pharmacology
Intestinal Mucosa drug effects
Polymers pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1540-0514
- Volume :
- 36
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Shock (Augusta, Ga.)
- Publication Type :
- Academic Journal
- Accession number :
- 21937955
- Full Text :
- https://doi.org/10.1097/SHK.0b013e31822d8de1