sodium-taurodeoxycholate and Ischemia

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 (3)H-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 (3)H-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 Ca(2+)-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 Ca(2+) dependent.

Topics: Animals; Bile Acids and Salts; Calcium; Deoxycholic Acid; Female; Ileum; Ischemia; Male; Microscopy, Electron; Osmolar Concentration; Permeability; Recovery of Function; Swine; Taurodeoxycholic Acid

The influence of lysophosphatidylcholine (lysoPC), taurodeoxycholate (TDC), and taurochenodeoxycholate (TCDC) on the permeability properties of the ischaemic small-intestinal mucosa was investigated. We first studied the effect of ischaemia alone, then of lysoPC, TDC, or TCDC alone, and finally of ischaemia together with lysoPC, TDC, or TCDC on the permeability to sodium fluorescein in a ligated loop of the distal ileum in the rat. Longer periods of ischaemia alone (10 min or more) caused increased permeability, as did high concentrations (10 mM) of any of the agents. Low concentrations (1 mM) of lysoPC alone did not alter the gut permeability, but it significantly potentiated the increased permeability caused by 30 min of ischaemia. In contrast, 1 mM TDC or TCDC did not influence the permeability after 30 min of ischaemia. These findings imply that the ischaemic small intestine may be damaged by small amounts of lysoPC, with increased absorption of potentially pathogenic compounds as a possible consequence. They also point to the possibility that endogenously formed lysoPC may play a role in the mucosal damage and the increased permeability that occurs after small-intestinal ischaemia.

Topics: Animals; Cell Membrane Permeability; Female; Intestinal Mucosa; Intestine, Small; Ischemia; Lysophosphatidylcholines; Rats; Rats, Inbred Strains; Taurochenodeoxycholic Acid; Taurodeoxycholic Acid

Although recent clinical reports suggest that greater than normal amounts of dihydroxy secondary bile acids appear in the gastric content of patients with postoperative alkaline reflux gastritis, the pathophysiologic significance of these observations is unclear. We addressed this problem by usiong chambered ex vivo wedges of proximal canine gastric wall. The effects of 1 and 2 mM concentrations of the dihydroxy secondary bile acid, taurodeoxycholic, were compared with those of its parent trihydroxy primary bile acid, taurocholic. The parameters of mucosal function evaluated included the net flux of hydrogen ion, the transmural electrical potential difference, mucosal blood flow determined by radiolabeled microsphere embolization, and the severity of mucosal damage induced in mucosa rendered ischemic by wedge-specific intra-arterial low-dose vasopressin infusin. The results indicate that at each concentration in both ischemic and nonischemic mucosa the dihydroxy secondary bile acid induced a greater depression in potential difference, a more profound increase in mucosal permeability to hydrogen ion, and in ischemic mucosa a more severe degree of gross mucosal damage than did the trihydroxy primary bile acid. These effects may be related to a greater lipid solubility and consequent capacity to disrupt cell membranes.

Topics: Animals; Deoxycholic Acid; Dogs; Female; Gastric Mucosa; Ischemia; Male; Stomach Ulcer; Taurocholic Acid; Taurodeoxycholic Acid