Ursodeoxycholic acid ameliorates ibuprofen-induced enteropathy in the rat.
BACKGROUND
The objective of the study was to determine whether ursodeoxycholic acid (Ursodiol) is protective against ibuprofen (IBU)-induced enteropathy.


METHODS
Using the chronically catheterized rat model, IBU (60 mg/kg body weight per day) was infused via the gastric catheter twice daily. Pancreatic enzyme (PE; 10,000 U lipase/kg body weight per day) and Ursodiol (10 mg/kg body weight per day) in two doses were infused via the duodenal catheter. Rats were assigned to one of six treatment groups and were administered treatment for 20 days: control, IBU, PE, IBU + PE, IBU + Ursodiol, and IBU + PE + Ursodiol. The entire jejunum, ileum, cecum, and colon were available for histologic analysis using previously described techniques.


RESULTS
Addition of Ursodiol to high-dose IBU and normal doses of PE showed a significant reduction in the percentage of rats with ulcers (P < 0.05), total number of serositis events (P < 0.01), total number of severe ulcers (P < 0.001), and an absence of ulcers in the large intestine.


CONCLUSIONS
Ursodiol, the drug of choice for the treatment of cystic fibrosis liver disease, may offer a safe method of using high-dose IBU in these patients by ameliorating the enteropathy.
Lloyd-Still
J D
JD
Department of Pediatrics, Rush Medical College, Chicago, Illinois, USA.
Beno
D W
DW
Uhing
M R
MR
Jiyamapa-Serna
V A
VA
Kimura
R E
RE
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D002404:Catheterization; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy; D004195:Disease Models, Animal; D007052:Ibuprofen / Q000008:administration & dosage / Q000633:toxicity*; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000517:prevention & control; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008049:Lipase / Q000008:administration & dosage; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012700:Serositis / Q000139:chemically induced / Q000517:prevention & control; D014456:Ulcer / Q000139:chemically induced / Q000517:prevention & control; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D008049:Lipase; D007052:Ibuprofen