Submitted on July 21, 2003
Accepted on March 26, 2004
Physiologic concentrations of bile salts inhibit recovery of ischemic-injured porcine ileum
Nigel B. Campbell1, Craig G. Ruaux2, Donnie E. Shifflett1, Jorg M. Steiner2, David A. Williams2, and Anthony T. Blikslager1*
1 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
2 Gastrointestinal Laboratory, Department of Small Animal Medicine and Surgery, College of Veterinary Medicien, Texas A&M University, Raleigh, NC, USA
* To whom correspondence should be addressed. E-mail: Anthony_Blikslager{at}ncsu.edu.
Physiologic concentrations of bile salts inhibit recovery of ischemic-injured porcine
ileum - 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 physiologic
concentrations of deoxycholic acid in recovery of mucosal barrier function. Porcine ileum was
subjected to 45-minutes 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-minutes, associated with significant reductions in mucosal-to-serosal
3H-mannitol flux. However, treatment of ischemic-injured tissues with 10-5M deoxycholic acid
significantly inhibited recovery of TER with significant increases in mucosal-to-serosal 3H-mannitol
flux, whereas 10-6M deoxycholic acid had no effect. Histologic evaluation at 120-minutes revealed complete restitution regardless of treatment, indicating the breakdown in
barrier function was due to changes in paracellular permeability. Similar effects were noted with
application of 10-5M taurodeoxycholic acid, and the effects of deoxycholic acid were reversed
with application of the Ca2+ mobilizing agent thapsigargin. Deoxycholic acid at physiologic
concentrations significantly impairs recovery of epithelial barrier function by an effect on
paracellular pathways, and these effects appear to be Ca2+-dependent.
