Ursodeoxycholic acid ameliorates experimental ileitis counteracting intestinal barrier dysfunction and oxidative stress.
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.
Bernardes-Silva
Carlos Felipe
CF
Department of Gastroenterology School of Medicine, University of São Paulo, São Paulo, Brazil. carlosfelipebs@uol.com.br
Damião
Adérson O M C
AO
Sipahi
Aytan M
AM
Laurindo
Francisco R M
FR
Iriya
Kiyoshi
K
Lopasso
Fabio P
FP
Buchpiguel
Carlos A
CA
Lordello
Maria Laura L
ML
Agostinho
Carmem L O
CL
Laudanna
Antonio A
AA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D004195:Disease Models, Animal; D007079:Ileitis / Q000139:chemically induced / Q000503:physiopathology*; D007213:Indomethacin / Q000633:toxicity; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017382:Reactive Oxygen Species; D014580:Ursodeoxycholic Acid; D007213:Indomethacin