Transmucosal Gastric Leak Induced by Proton Pump Inhibitors |
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Authors: | Lisa J. Murray Melissa Gabello David S. Rudolph Christopher P. Farrell Melissa Morgan Aaron P. Martin James C. Underwood M. Carmen Valenzano James M. Mullin |
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Affiliation: | (1) Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, USA;(2) Department of Biology, Saint Joseph’s University, Philadelphia, PA 19131, USA;(3) Department of Medicine, Lankenau Hospital, Wynnewood, PA 19096, USA;(4) Division of Gastroenterology, Lankenau Hospital, Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, USA |
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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 14C-[d]-mannitol (MW 182.17) across the gastric mucosa increased by a mean of 68% immediately following the addition of 200 μM omeprazole. This flux increase was bidirectional. Omeprazole also increased the paracellular permeability to larger radiolabeled probes, including 14C-sucrose (MW 342.3) and 14C-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. Support: AstraZeneca, the Pennsylvania Department of Health, and the Sharpe/Strumia Foundation. |
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Keywords: | Omeprazole Proton pump inhibitor Gastric leak Epithelial permeability Tight junction |
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