title: Role of stasis and oxidative stress in ileal pouch inflammation.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: K O
authors.initials: KO
authors.lastname: Shebani
authors.forename: A F
authors.initials: AF
authors.lastname: Stucchi
authors.forename: J P
authors.initials: JP
authors.lastname: McClung
authors.forename: E R
authors.initials: ER
authors.lastname: Beer
authors.forename: W W
authors.initials: WW
authors.lastname: LaMorte
authors.forename: J M
authors.initials: JM
authors.lastname: Becker
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology; D028441:F2-Isoprostanes; D005769:Gastrointestinal Motility; D007082:Ileum / Q000201:enzymology; D008297:Male; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D019449:Pouchitis / Q000209:etiology*; D051381:Rats; D011917:Rats, Inbred Lew; D015430:Weight Gain
chemical_list: D000975:Antioxidants; D028441:F2-Isoprostanes; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D009195:Peroxidase