Role of dietary fibres, intestinal hypermotility and leukotrienes in the pathogenesis of NSAID-induced small intestinal ulcers in cats

Background: Recent advances in endoscopy have revealed that non-steroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the human small intestine. However, the mechanism of intestinal ulcer formation is still unclear. Aims: The role of dietary fibre (DF), intestinal motility and leukotrienes (LTs) in the formation of small intestinal ulcers induced by indomethacin (IND) was investigated in cats. Methods: Several types of diets containing DF at various percentages were given to animals twice daily during the experiment. IND was administered orally once daily after the morning meal for 3 days, and the area of mucosal lesions in the intestine was measured. Gastrointestinal motility was measured using a telemetry system in conscious cats implanted with force transducers. Results: In cats fed regular dry food containing 2.8% DF, IND (3 mg/ kg, p.o.) significantly increased the motility of the lower half of the small intestine and produced many severe lesions; the total lesion area was 7.7 (SEM 2.0) cm(2) (n= 5). The lesions were markedly decreased with the low-DF diet (0.4%) and increased with the high-DF diet (7.2%). The lesion area was 0.1 (SEM 0.1) cm(2) (p < 0.05) and 18.2 (SEM 4.1) cm(2) (p < 0.05), respectively. Supplementation with insoluble DF (6% cellulose), but not soluble DF (pectin), in the low-DF diet increased the lesion area significantly. The hypermotility and lesion formation in the small intestine induced by IND were significantly (p < 0.05) inhibited by AA-861 (a 5-lipoxygenase inhibitor), pranlukast (a LT receptor antagonist) or atropine. Conclusions: Insoluble DF, intestinal hypermotility, leukotrienes and cholinergic pathways are implicated in the pathogenesis of small intestinal ulcers induced by NSAIDs.