Sulphydryl blocker induced small intestinal inflammation in rats: a new model mimicking Crohn's disease

D Rachmilewitz, E Okon, F Karmeli

Departments of Medicine and Pathology, Hadassah University Hospital, Mount Scopus, Hebrew University, Hadassah Medical School, Jerusalem, Israel

Correspondence to: Daniel Rachmilewitz, MD, Head, Department of Medicine, Hadassah University Hospital, Mount Scopus, PO Box 24035, Jerusalem 91240, Israel.

Accepted for publication 10 March 1997

BackgroundSulphydryl compounds are essential for maintaining mucosal integrity in the gastrointestinal tract.
AimTo characterise a model of experimental inflammation in the small intestine induced by a sulphydryl blocker.
MethodsInflammation in the small intestine was induced in rats by intrajejunal administration of 0.1 ml 2% iodoacetamide. The possible amelioration of the damage induced was modulated by intragastric administration of TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl; 50 mg/100 g body weight), ketotifen (200 µg/100 g body weight) or by addition of L-NAME (N^G-nitro-L-arginine methyl ester; 0.1 mg/ml) or apocynin (120 µg/ml) to the drinking water. Rats were sacrificed at various time intervals, the small intestine resected, weighed, macroscopic lesions were assessed, and mucosal generation of inflammatory mediators and nitric oxide synthase activity were determined.
ResultsIntrajejunal administration of iodoacetamide induced, after one week, multifocal mucosal erosions, ulcerations with granulomas and giant Langhans cells. At two weeks, the mucosa was almost macroscopically intact but histologically epithelial granuloma and giant cells were present. Myeloperoxidase activity was increased in the first 24 hours, one week later mucosal nitric oxide synthase activity and generation of leukotriene B4, leukotriene C4 and thromboxane B2 were increased, whereas prostaglandin E2 generation was decreased notably. Ketotifen and apocynin significantly decreased the extent of injury which was not affected by TEMPOL or L-NAME.
ConclusionsJejunal inflammation induced by the sulphydryl blocker, iodoacetamide, resembles the pathological changes in Crohn's disease. The protective effect of ketotifen and apocynin indicates the contribution of O₂ and pro-inflammatory mediators to the pathogenesis of the damage, and may be a novel approach to the treatment of inflammatory bowel disease.
(GUT 1997;41:358-365)

Keywords: iodoacetamide;  TEMPOL;  ketotifen;  apocynin;  NO synthase