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Transmucosal Gastric Leak Induced by Proton Pump Inhibitors

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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.

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Acknowledgments

We would like to thank AstraZeneca for supplying us with esomeprazole. Grant support from the Pennsylvania Department of Health was instrumental in conducting this work. The Department specifically disclaims responsibility for any analyses, interpretations, or conclusions presented in this paper. Additional thanks go to the animal care staff at Lankenau Hospital for housing the rats used in these studies and to Gwen Gilliard for her assistance with the animals. Thanks also go to the Editorial Department at the Lankenau Institute for Medical Research for their support in the preparation of this manuscript and to Dr. Thomas Stamato for his critical reading of the manuscript.

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Authors and Affiliations

  1. Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA, 19096, USA

    Lisa J. Murray, Melissa Gabello, Aaron P. Martin, James C. Underwood & M. Carmen Valenzano

  2. Department of Biology, Saint Joseph’s University, Philadelphia, PA, 19131, USA

    Lisa J. Murray & Melissa Gabello

  3. Department of Medicine, Lankenau Hospital, Wynnewood, PA, 19096, USA

    David S. Rudolph, Christopher P. Farrell & Melissa Morgan

  4. Division of Gastroenterology, Lankenau Hospital, Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA, 19096, USA

    James M. Mullin

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  1. Lisa J. Murray
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Correspondence to James M. Mullin.

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Support: AstraZeneca, the Pennsylvania Department of Health, and the Sharpe/Strumia Foundation.

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Murray, L.J., Gabello, M., Rudolph, D.S. et al. Transmucosal Gastric Leak Induced by Proton Pump Inhibitors. Dig Dis Sci 54, 1408–1417 (2009). https://doi.org/10.1007/s10620-008-0528-z

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