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.


OBJECTIVE
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.
Satoh
H
H
Department of Pharmacological and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Shiotani
S
S
Otsuka
N
N
Hatao
K
K
Nishimura
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002415:Cats; D004032:Diet; D004043:Dietary Fiber / Q000008:administration & dosage / Q000009:adverse effects*; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D004435:Eating; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D007421:Intestine, Small; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D015289:Leukotrienes / Q000502:physiology; D008297:Male; D014456:Ulcer / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004043:Dietary Fiber; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D007213:Indomethacin