Dose-related effects of chenodeoxycholic acid in the rabbit colon

The effects of bile acid (BA) concentration on fluid secretion, mucus secretion, and mucosal damage were investigated during dose-response studies in the rabbit colon with 1, 2.5, and 5 mM sodium chenodeoxycholate (NaCDC). 1 mM NaCDC resulted in mucus secretion followed by mucosal damage but no change in fluid transport was observed. At 2.5 mM concentration, mucus secretion and mucosal damage were evident within 1 hr of perfusion whereas fluid secretion developed in the second hour only. At 5 mM concentrations, all changes occurred simultaneously. The magnitude of changes increased with the concentration of BA perfused. These results are consistent with the hypothesis that mucus secretion with loss of its cytoprotective effect precedes, and thus may permit, the detergent effects of the di-alpha-hydroxy bile acid on the mucosa, resulting in mucosal damage. Both these effects precede changes in fluid and electrolyte transport.