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- Title
Transmucosal gastric leak induced by proton pump inhibitors.
- Authors
Murray, Lisa J.; Gabello, Melissa; Rudolph, David S.; Farrell, Christopher P.; Morgan, Melissa; Martin, Aaron P.; Underwood, James C.; Valenzano, M. Carmen; Mullin, James M.
- Abstract
Despite their remarkable safety profile and lack of clinical side effects, proton pump inhibitors (PPIs) induce a transmucosal gastric leak to non-electrolyte probes of various sizes. The ex vivo addition of PPIs to isolated rat gastric corpus increases transmucosal permeability in a dose-dependent manner, which corresponds with PPIs' dose-dependent inhibition of acid secretion. Upon the addition of omeprazole, lansoprazole, or esomeprazole, a small decrease in transepithelial resistance and the concomitant stimulation of short circuit current was observed. Additionally, transepithelial flux of (14)C-[D]-mannitol (MW 182.17) across the gastric mucosa increased by a mean of 68% immediately following the addition of 200 microM omeprazole. This flux increase was bidirectional. Omeprazole also increased the paracellular permeability to larger radiolabeled probes, including (14)C-sucrose (MW 342.3) and (14)C-polyethylene glycol (MW 4,000) by 118% and 350%, respectively. However, the flux of still larger probes, 10,000 and 70,000 MW dextrans, was not increased. Because PPIs are so widely used and are assumed to be innocuous, this transmucosal gastric leak must be further investigated, as it may carry considerable biomedical implications.
- Subjects
OMEPRAZOLE; PROTON pump inhibitors; TIGHT junctions; GASTRIC mucosa; GASTRIC diseases; ANIMAL experimentation; COMPARATIVE studies; DOSE-effect relationship in pharmacology; EPITHELIUM; GASTROINTESTINAL agents; HYDROGEN-ion concentration; RESEARCH methodology; MEDICAL cooperation; PERMEABILITY; RATS; RESEARCH; SULFUR compounds; EVALUATION research; ESOMEPRAZOLE; LANSOPRAZOLE; IN vitro studies
- Publication
Digestive Diseases & Sciences, 2009, Vol 54, Issue 7, p1408
- ISSN
0163-2116
- Publication type
journal article
- DOI
10.1007/s10620-008-0528-z