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Acetaminophen changes paracellular transport activity through regulation of the tight junction protein in an intestinal barrier model

Authors :
Klaus Schröder
Mohammad Reza Lornejad-Schäfer
Christine Schäfer
Source :
BMC Pharmacology & Toxicology
Publication Year :
2012
Publisher :
Springer Science and Business Media LLC, 2012.

Abstract

permeability of the small molecules Lucifer Yellow (ca. 520 Da) and FITC-dextran (3– 5k Da) but not of large molecules (40 kDa FITC-dextran). The tight junction protein ZO-1 and its tyrosine phosphorylation were upregulated after 24 h treatment with APAP. Conclusions Tight junction proteins play an important role in maintaining the intestinal barrier function. We assume that APAP affects the paracellular transport pathway through disassembly of the tight junction. We suppose that APAP leads to remodelling of the tight junction protein ZO-1 through changes in the level of protein expression and in tyrosine phosphorylation. APAP may reduce the bioavailability of co-administered substances through remodelling the tight junction by regulating ZO-1 and its tyrosine phosphorylation. As a result, the paracellular transport activity for small molecules is decreased as is net intestinal absorption.

Details

ISSN :
20506511
Volume :
13
Database :
OpenAIRE
Journal :
BMC Pharmacology and Toxicology
Accession number :
edsair.doi.dedup.....4a48c373f0f519f5371a7d0d70866af0
Full Text :
https://doi.org/10.1186/2050-6511-13-s1-a12