J Vet Sci.  2006 Jun;7(2):137-141. 10.4142/jvs.2006.7.2.137.

Experimental peritonitis induced by oral administration of indomethacin in Mongolian gerbils

Affiliations
  • 1Animal Disease Research Unit, Center for Animal Resources Development, Wonkwang University, Iksan 570-749, Korea. kimoj@wonkwang.ac.kr
  • 2Institute of Life Science and Natural Resources, College of Life Science and Natural Resources, Wonkwang University, Iksan 570-749, Korea. kimoj@wonkwang.ac.kr
  • 3Department of Laboratory Animal Sciences, College of Medicine, Seoul National University, Seoul 110-719, Korea.

Abstract

The possibility of inducing peritoneal inflammation in three murine species (gerbils, rats and mice) via the oral administration of indomethacin was investigated with the overall aim of developing an experimental animal model for human peritonitis. Gerbils given high doses of indomethacin at a rate of 30 mg and 40 mg/kg body weight showed swelling of the abdomen, depression and dyspnea within 4 days after the treatment. The severity of the clinical symptoms increased with time. The animals were confirmed as having developed peritonitis based on the pathological features including inflammation of the peritoneum, and fibrinous adhesion of the abdominal organs in the abdominal cavity. The severity of peritonitis increased with increasing dose of indomethacin, and was not related to the gender of the animal. On the other hand, peritoneal inflammation did not develop in the rats and mice even at high doses. Therefore, the administration of 30 mg/kg body weight of indomethacin is an effective and simple method of inducing peritonitis in 5-week-old Mongolian gerbils. The animal peritonitis model used in this study can be used as an effective tool for examining potential therapeutic compounds for preventing peritoneal damage during peritonitis, and provide insight into the pathophysiology of peritonitis.

Keyword

animal model; indomethacin; Mongolian gerbil; peritonitis

MeSH Terms

Administration, Oral
Animals
Dose-Response Relationship, Drug
Female
*Gerbillinae
Indomethacin/*administration&dosage/*toxicity
Inflammation/chemically induced/pathology
Male
Mice
Mice, Inbred ICR
Peritonitis/*chemically induced/pathology
Rats
Rats, Sprague-Dawley
Specific Pathogen-Free Organisms

Figure

  • Fig. 1 A representative Mongolian gerbil treated with high-dosed indomethacin is shown. The macroscopic findings were a swelling of the abdomen, ascites, a swelling of the colon and fibrinous adhesion of the abdominal organs (a). The gastrointestinal loops adhered to each other along their entirety (b).

  • Fig. 2 Histopathological findings of a gerbil given a high dosed of indomethacin. The parietal peritoneum was thickened including edematous changes, and the fibrosis infiltration of mononuclear cells was observed (a, b). H&E stain, ×200. The liver showed a thickened serous membrane mainly due to collagen deposits and fibrosis (c). H&E stain, ×400. In the pancreas, there was fibrosis of the visceral peritoneum and the infiltration of mononuclear cells (d). H&E stain, ×400.


Reference

1. Allison MC, Howatson AG, Torrance CJ, Lee FD, Russell RI. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. N Engl J Med. 1992. 327:749–754.
Article
2. Bjarnason I, Williams P, So A, Zanelli GD, Levi AJ, Gumpel JM, Peters TJ, Ansell B. Intestinal permeability and inflammation in rheumatoid arthritis: effects of nonsteroidal anti-inflammatory drugs. Lancet. 1984. 2:1171–1174.
Article
3. Bjarnason I, Williams P, Smethurst P, Peters TJ, Levi AJ. Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine. Gut. 1986. 27:1292–1297.
Article
4. Bosscha K, Reijnders K, Hulstaert PF, Algra A, van der Werken C. Prognostic scoring systems to predict outcome in peritonitis and intra-abdominal sepsis. Br J Surg. 1997. 84:1532–1534.
Article
5. Christou NV, Barie PS, Dellinger EP, Waymack JP, Stone HH. Surgical Infection Society intra-abdominal infection study: Prospective evaluation of management techniques and outcome. Arch Surg. 1993. 128:193–198.
Article
6. Dobbie JW. Pathogenesis of peritoneal fibrosing syndromes (sclerosing peritonitis) in peritoneal dialysis. Perit Dial Int. 1992. 12:14–27.
Article
7. Fierer J, Swancutt MA, Heumann D, Golenbock D. The role of lipopolysaccharide binding protein in resistance to Salmonella infections in mice. J Immunol. 2002. 168:6396–6403.
Article
8. Fink MP, Heard SO. Laboratory models of sepsis and septic shock. J Surg Res. 1990. 49:186–196.
Article
9. Lengeling RW, Mitros FA, Brennan JA, Schulze KS. Ulcerative ileitis encountered at ileo-colonoscopy: likely role of nonsteroidal agents. Clin Gastroenterol Hepatol. 2003. 1:160–169.
Article
10. Morris AJ, MacKenzie JF, Madhok R, Sturrock RD, Capell HA. Enteroscopic diagnosis of small bowel ulceration in patients receiving non-steroidal anti-inflammatory drugs. Lancet. 1991. 337:520.
Article
11. Mun KC, Yeo MY, Kim SP, Kim HC, Kwak CS. Chronic peritoneal inflammation by cyanate in rats. Perit Dial Int. 2000. 20:699–702.
Article
12. Ohmann C, Yang Q, Hau T, Wacha H. Peritonitis Study Group of the Surgical Infection Society Europe. Prognostic modelling in peritonitis. Eur J Surg. 1997. 163:53–60.
13. Rooney PJ, Jenkins RT, Smith KM, Coates G. 111Indium-labelled polymorphonuclear leucocyte scans in rheumatoid arthritis - an important clinical cause of false positive results. Br J Rheumatol. 1986. 25:167–170.
Article
14. Slingeneyer A. Preliminary report on a cooperative international study on sclerosing encapsulating peritonitis. Contrib Nephrol. 1987. 57:239–247.
Article
15. Somasundaram S, Hayllar H, Rafi S, Wrigglesworth JM, MacPherson AJ, Bjarnason I. The biochemical basis of non-steroidal anti-inflammatory drug-induced damage to the gastrointestinal tract: a review and a hypothesis. Scand J Gastroenterol. 1995. 30:289–299.
Article
16. Tanaka A, Hase S, Miyazawa T, Takeuchi K. Up-regulation of cyclooxygenase-2 by inhibition of cyclooxygenase-1: a key to nonsteroidal anti-inflammatory drug-induced intestinal damage. J Pharmacol Exp Ther. 2002. 300:754–761.
Article
17. Tibble JA, Sigthorsson G, Foster R, Scott D, Fagerhol MK, Roseth A, Bjarnason I. High prevalence of NSAID enteropathy as shown by a simple fecal test. Gut. 1999. 45:362–366.
Article
18. Topley N. The host's initial response to peritoneal infection: the pivotal role of the mesothelial cell. Perit Dial Int. 1995. 15:116–117.
Article
19. Yang AH, Chen JY, Lin YP, Huang TP, Wu CW. Peritoneal dialysis solution induces apoptosis of mesothelial cells. Kidney Int. 1997. 51:1280–1288.
Article
Full Text Links
  • JVS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr