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Intestinal site‐dependent susceptibility to chronic indomethacin in the rat: a morphological and biochemical study
Author(s) -
NYGÅRD G.,
ANTHONY A.,
KHAN K.,
BOUNDS S. V. J.,
CALDWELL J.,
DHILLON A. P.,
POUNDER R. E.,
WAKEFIELD A. J.
Publication year - 1995
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.1995.tb00398.x
Subject(s) - caecum , small intestine , medicine , prostaglandin , thromboxane b2 , leukotriene , leukotriene b4 , large intestine , endocrinology , thromboxane , ingestion , cecum , gastroenterology , inflammation , platelet , asthma
SUMMARY Background : The cyclo‐oxygenase inhibitor indomethacin induces a pattern of gastrointestinal injury in the rat that is site‐dependent. This study compared the extent of injury to different regions of the rat intestine (small intestine, caecum and colon) with the corresponding changes in arachidonic acid metabolism in these areas, following long‐term, low‐dose indomethachin. Methods : Rats (eight per group) received either indomethacin (3 mg.kg/day) or control diet for either 6 or 12 weeks. At termination animals were bled, examined both macroscopically and microscopically for ulcers, and assayed for blood thromboxane B 2 , intestinal tissue prostaglandin E 2 content and production of leukotriene B 4 . In a further eight animals luminal indomethacin concentrations from the small intestine, caecum and colon were measured following 6 weeks of chronic drug ingestion. Results : At 6 weeks, macroscopic ulcers were observed in 2/8 (small intestine), 3/8 (caecum) and 1/8 (colon) animals. The corresponding ratios at 12 weeks were 5/8, 8/8 and 0/8. In control animals, a site‐dependent gradient of the prostaglandin E 2 concentration was found. In indomethacin‐dosed animals the intestinal prostaglandin E 2 content was reduced significantly in the caecum at 6 weeks, and in all tissues at 12 weeks. An increased leukotriene B 4 production was observed in the caecum only, at 12 weeks ( P < 0.01), and the blood thromboxane B 2 was reduced at both time points ( P < 0.05). Conclusion : There is a site‐dependent gradient of the prostaglandin E 2 concentration in the rat intestine. The rat caecum is particularly sensitive to long‐term low‐dose indomethacin, both in terms of chronic intestinal inflammation and changes in prostanoid metabolism. This site‐dependent degree of injury may be associated with a local cyclo‐oxygenase inhibition.