Effect of ursodeoxycholic acid on the inflammatory activity of indomethacin-induced intestinal inflammation in rats.
The beneficial effects of ursodeoxycholic acid (UDCA) in primary biliary cirrhosis are supposed to be mediated in part by immunological mechanisms. In this study, we have tested whether ursodeoxycholic acid also ameliorates intestinal inflammation induced by indomethacin in rats. Intestinal inflammation was induced in rats by two injections of indomethacin (7.5 mg/kg body weight) 24 h apart. To study its effects on acute inflammation, UDCA (10 mg/kg body weight) was given for three days starting with the first administration of indomethacin; for effects on chronic inflammation, UDCA was given 24 h after the first indomethacin injection for eight days. Rats were sacrificed at days 3 and 9, respectively. In acute inflammation a significant decrease of intestinal injury was observed with UDCA treatment (macroscopic score: 3.00 +/- 0.83 vs. 6.55 +/- 0.53 in controls; p < 0.01; microscopic score: 1.66 +/- 0.28 vs. 2.89 +/- 0.35 in controls; p < 0.05). In chronic inflammation the effects of UDCA treatment were less marked due to a general decline in intestinal injury. Nevertheless a significant decrease in the macroscopic injury score (3.67 +/- 0.62 vs. 1.55 +/- 0.29 in UDCA treated rats; p < 0.01) was observed. Also, there was a significant increase in body weight of UDCA treated rats after nine days compared to controls (28.8% vs. 16% increased body weight in controls; p < 0.01). Thus, ursodeoxycholic acid attenuates the severity of acute damage of small bowel and the development of chronic intestinal inflammation induced by indomethacin in rats.
Kullmann
F
F
Department of Internal Medicine I, University of Regensburg, FRG.
Gross
V
V
Rüschoff
J
J
Arndt
H
H
Benda
W
W
Winkler von Mohrenfels
A
A
Schölmerich
J
J
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004751:Enteritis / Q000139:chemically induced* / Q000473:pathology; D007213:Indomethacin / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014580:Ursodeoxycholic Acid; D007213:Indomethacin