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Am J Physiol Gastrointest Liver Physiol 287: G399-G407, 2004. First published April 15, 2004; doi:10.1152/ajpgi.00310.2003
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MUCOSAL BIOLOGY

Physiological concentrations of bile salts inhibit recovery of ischemic-injured porcine ileum

Nigel B. Campbell,1 Craig G. Ruaux,2 Donnie E. Shifflett,1 Jöerg M. Steiner,2 David A. Williams,2 and Anthony T. Blikslager1

1Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606; and 2Gastrointestinal Laboratory, Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843

Submitted 21 July 2003 ; accepted in final form 26 March 2004

We have previously shown rapid in vitro recovery of barrier function in porcine ischemic-injured ileal mucosa, attributable principally to reductions in paracellular permeability. However, these experiments did not take into account the effects of luminal contents, such as bile salts. Therefore, the objective of this study was to evaluate the role of physiological concentrations of deoxycholic acid in recovery of mucosal barrier function. Porcine ileum was subjected to 45 min of ischemia, after which mucosa was mounted in Ussing chambers and exposed to varying concentrations of deoxycholic acid. The ischemic episode resulted in significant reductions in transepithelial electrical resistance (TER), which recovered to control levels of TER within 120 min, associated with significant reductions in mucosal-to-serosal 3H-labeled mannitol flux. However, treatment of ischemic-injured tissues with 10–5 M deoxycholic acid significantly inhibited recovery of TER with significant increases in mucosal-to-serosal 3H-labeled mannitol flux, whereas 10–6 M deoxycholic acid had no effect. Histological evaluation at 120 min revealed complete restitution regardless of treatment, indicating that the breakdown in barrier function was due to changes in paracellular permeability. Similar effects were noted with the application of 10–5 M taurodeoxycholic acid, and the effects of deoxycholic acid were reversed with application of the Ca2+-mobilizing agent thapsigargin. Deoxycholic acid at physiological concentrations significantly impairs recovery of epithelial barrier function by an effect on paracellular pathways, and these effects appear to be Ca2+ dependent.

mucosa; barrier function; deoxycholic acid; tight junction


Address for reprint requests and other correspondence: A. T. Blikslager, Dept. of Clinical Sciences, College of Veterinary Medicine, North Carolina State Univ., Raleigh, NC 27606 (E-mail: Anthony_Blikslager{at}ncsu.edu).






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