Role of Stasis and Oxidative Stress in Ileal Pouch Inflammation

• Published in: The Journal of surgical research 2000-05, Vol.90 (1), p.67-75
• Main Authors: Shebani, Khaled O., Stucchi, Arthur F., McClung, James P., Beer, Eve R., LaMorte, Wayne W., Becker, James M.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Dinoprost - analogs & derivatives; Dinoprost - pharmacology; F2-Isoprostanes; Gastrointestinal Motility; ileal inflammation; Ileum - enzymology; Male; Oxidative Stress; Peroxidase - metabolism; pouchitis; Pouchitis - etiology; Rats; Rats, Inbred Lew; reactive oxygen metabolites; stasis; Weight Gain
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.2000.5842

Background. Although ileal pouch–anal anastomosis has become the operation of choice for patients with chronic ulcerative colitis and familial adenomatous polyposis coli, ileal pouch inflammation or pouchitis remains a significant postoperative complication. Numerous factors such as fecal stasis have been implicated in the etiology of pouchitis; however, pouchitis remains poorly understood due to the lack of a small animal model. One of the primary goals of this study was to surgically create a reservoir or U-pouch in the ileum of a rat in which stasis would occur in a manner that was unimpeded by other complicating factors such as a colectomy. This model would allow investigation of the hypothesis that intestinal stasis leads to biochemical changes that predispose the ileal pouch to inflammation and oxidative stress. Materials and methods. A U-pouch was surgically created in the terminal ileum of Lewis rats just proximal to the ileocecal valve without a colectomy. Stasis was assessed by serial barium radiographs over 48 h. Thirty days after surgery, mucosa was obtained from the ileal U-pouches and nonoperated ileum to assess inflammation and neutrophil infiltration histologically and by measuring myeloperoxidase activity. Oxidative stress was assessed by measuring 8-isoprostane levels in urine. Once the model was validated and it was established that stasis and inflammation occurred in the pouch, either vitamin E or allopurinol was administered for 30 days after which myeloperoxidase and 8-isoprostane levels were again measured. Results. In our experimental model, ileal stasis resulted in increases in both mucosal myeloperoxidase activity and urinary 8-isoprostane levels, suggesting that oxidative stress was associated with stasis. Thirty-day treatment with vitamin E or allopurinol reduced ileal myeloperoxidase activity and urinary 8-isoprostane levels. Conclusion. These studies demonstrated that stasis in the ileum occurred and was associated with neutrophil infiltration and oxidative stress. Antioxidant treatment reduced the inflammatory response suggesting a role for antioxidant therapy in the treatment of pouchitis.