Radiation decreases murine small intestinal HCO₃⁻ secretion

Abstract

Purpose: While secretagogue-induced diarrhea is rich in chloride (Cl⁻) and bicarbonate (HCO₃ ⁻) anions, little is known about diarrhea or its anionic composition following irradiation. We performed studies to characterize the differences between cyclic adenosine monophosphate (cAMP)-stimulated anion secretions in irradiated and non-irradiated mice.

Materials and methods: HCO₃ ⁻ secretion was examined in basal, cAMP-stimulated, and irradiated jejunal tissues from BALB/c (Bagg albino) mice. The abdomens of the mice were γ-irradiated using a caesium-137 source.

Results: Ussing-chamber experiments performed in an HCO₃⁻-containing, Cl⁻-free solution on the bath side showed inhibition of HCO₃⁻ in irradiated mice. Non-irradiated mice exhibited bumetanide-sensitive and insensitive current, while irradiated mice displayed bumetanide-sensitive current. pH-stat experiments showed inhibition of basal and cAMP-stimulated HCO₃⁻ secretions in irradiated mice. Immunohistochemistry and Western blot analysis displayed a sodium-bicarbonate cotransporter expression in the villus and not the crypt of non-irradiated mice, while its expression and protein levels decreased in irradiated mice.

Conclusions: Anion secretions in irradiated mice, being primarily Cl⁻ and minimally HCO₃⁻, differ from that of secretagogue-induced anion secretions. Understanding anion loss will help us correct electrolyte imbalances, while reduced HCO₃⁻ secretion in the upper-gastrointestinal tract might also have implications for irradiation-induced nausea and vomiting.

Keywords:

• Irradiation
• bicarbonate transport
• anion secretion

Acknowledgements

The authors would like to thank the University of Rochester Animal Care and Use Committee and Katherine Casey-Sawicki and Jessica Kirwan in the Research Office of the Department of Radiation Oncology at the University of Florida. We would like to acknowledge grant support from the Centers for Medical Countermeasures Against Radiation Program (1RC1AI078519-01) and the National Institute of Allergy and Infectious Diseases (U19-AI067733).

Declaration of interest:

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.