Ursodeoxycholic Acid Ameliorates Experimental Ileitis Counteracting Intestinal Barrier Dysfunction and Oxidative Stress

Abstract

The aim of this study was to evaluate the effect of ursodeoxycholic acid (UDCA) on intestinal permeability (IP) and reactive oxygen species (ROS) generation in indomethacin-induced enteropathy, a well-known experimental model of Crohn's disease. Seventy-eight male Wistar rats were randomly assigned to receive indomethacin, indomethacin + UDCA, or vehicles. Indomethacin induced a significant increase in the fraction of urinary excretion of 51Cr-EDTA following oral administration (7.9 +/- 1.3 vs 2.3 +/- 0.2%; P < 0.05) and lucigenin-amplified chemiluminescence in intestinal fragments ex vivo (10.1 +/- 1.9 vs 2.6 +/- 0.4 cpm x 10(3)/mg; P < 0.05) compared to controls. UDCA significantly reversed these effects (P < 0.05), without being incorporated in biliary bile acid composition (HPLC analysis). These findings support a local protective effect of UDCA in experimental ileitis by the modulation of intestinal barrier dysfunction and oxidative stress. In short, they provide insights into mechanisms of action of UDCA in intestinal inflammation and a new perspective on the treatment of Crohn's disease.

The effects of ciprofloxacin and ursodeoxycholic acid on bacterial translocation in obstructive jaundice

“…Again, inflammatory cell count of the intestinal wall was found to be significantly decreased in Group E. Intestinal oxidative stress was claimed to be responsible for obstructive jaundice-induced gut barrier dysfunction (2). It has been shown that UDCA has antioxidative properties (18) and immunomodulatory effects by decreasing cytokine production (19). Ciprofloxacin, possibly by decreasing overgrowth of gramnegative bacilli, potentiated the antiinflammatory effect of UDCA in this study.…”

Intestinal bile acid physiology and pathophysiology

“…Thus UDCA reduces intestinal permeability and oxidative stress in the indomethacin model of ileitis in the rat [123] . Similarly, UDCA counteracts ibuprofen intestinal ulceration in rats [124] .…”

A novel mechanism for gut barrier dysfunction by dietary fat: epithelial disruption by hydrophobic bile acids

“…Fatty feed increased the fecal concentration of DCA whereas it decreased the proportion of the more hydrophilic, tertiary bile acid ursodeoxycholic acid (UDCA) (19), which is potentially cytoprotective (2,10,18). The decrease in the proportion of fecal UDCA was related to disruption of the intestinal barrier (19).…”