A weakly acidic solution containing deoxycholic acid induces esophageal epithelial apoptosis and impairs integrity in an in vivo perfusion rabbit model
Pardon NA, Vicario M, Vanheel H, Vanuytsel T, Ceulemans LJ, Vieth M, Jimenez M, Tack J, Farré R (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 310
Pages Range: G487-G496
Journal Issue: 7
Abstract
Impaired esophageal mucosal integrity may be an important contributor in the pathophysiology of gastroesophageal reflux disease (GERD). Nevertheless, the effect of potentially harmful agents on epithelial integrity is mainly evaluated in vitro for a short period of time and the possible induction of epithelial apoptosis has been neglected. Our objective was to assess the effect of an acidic and weakly acidic solution containing deoxycholic acid (DCA) on the esophageal epithelium in an in vivo rabbit model of esophageal perfusion and to evaluate the role of the epithelial apoptosis. The esophagus of 55 anesthetized rabbits was perfused for 30 min with different solutions at pH 7.2, pH 5.0, pH 1.0, and pH 5.0 containing 200 and 500 μM DCA. Thereafter, animals were euthanized immediately or at 24 or 48 h after the perfusion. Transepithelial electrical resistance, epithelial dilated intercellular spaces, and apoptosis were assessed in Ussing chambers, by transmission electron microscopy, and by TUNEL staining, respectively. No macroscopic or major microscopic alterations were observed after the esophageal perfusions. The acidic and weakly acidic solution containing DCA induced similar long-lasting functional impairment of the epithelial integrity but different ultrastructural morphological changes. Only the solution containing DCA induced epithelial apoptosis in vivo and in vitro in rabbit and human tissue. In contrast to acid, a weakly acidic solution containing DCA induces epithelial apoptosis and a long-lasting impaired mucosal integrity. The presence of apoptotic cells in the esophageal epithelium may be used as a marker of impaired integrity and/or bile reflux exposure.
Involved external institutions
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Belgium (BE)
Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron
Spain (ES)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
Belgium (BE)
Klinikum Bayreuth
Germany (DE)
Centro de Investigación Biomédica en Red - Enfermedades Hepáticas y Digestivas (CIBERHD)
Spain (ES)
Belgium (BE)
Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron
Spain (ES)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
Belgium (BE)
Klinikum Bayreuth
Germany (DE)
Centro de Investigación Biomédica en Red - Enfermedades Hepáticas y Digestivas (CIBERHD)
Spain (ES)
How to cite
APA:
Pardon, N.A., Vicario, M., Vanheel, H., Vanuytsel, T., Ceulemans, L.J., Vieth, M.,... Farré, R. (2016). A weakly acidic solution containing deoxycholic acid induces esophageal epithelial apoptosis and impairs integrity in an in vivo perfusion rabbit model. American Journal of Physiology-Gastrointestinal and Liver Physiology, 310(7), G487-G496. https://doi.org/10.1152/ajpgi.00370.2015
MLA:
Pardon, Nicolas A., et al. "A weakly acidic solution containing deoxycholic acid induces esophageal epithelial apoptosis and impairs integrity in an in vivo perfusion rabbit model." American Journal of Physiology-Gastrointestinal and Liver Physiology 310.7 (2016): G487-G496.
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