We examined the effects of various
cyclooxygenase (COX) inhibitors on the healing of colonic lesions induced by
dextran sulfate sodium (DSS) in the rat. Colonic lesions were induced by 2.5% DSS in the
drinking water for 7 days, and then the animals were fed with tap water for subsequent 7 days.
Indomethacin (a nonselective COX inhibitor),
SC-560 (a selective COX-1 inhibitor), or
rofecoxib (a selective
COX-2 inhibitor) was given orally twice daily after termination of the DSS treatment. DSS treatment caused severe colonic lesions with a decrease in
body weight gain and colon length as well as an increase in
myeloperoxidase activity and
thiobarbituric acid reactant levels. The severity of
colitis gradually reduced, with an improvement of morphological and histological alterations. Daily administration of
indomethacin and
rofecoxib significantly delayed the healing of
colitis with deleterious influences on histological restitution as well as mucosal
inflammation, while
SC-560 had no effect. Although COX-1
mRNA was expressed in the colon without much alteration during the test period, the expression of COX-2 was upregulated with a peak on day 3 and decreased thereafter. The mucosal
prostaglandin E2 content in the colon showed a biphasic change, in parallel with that of the COX-2 expression. The increased
prostaglandin E2 production in the injured mucosa was attenuated by
indomethacin and
rofecoxib, but not by
SC-560. These results suggest that endogenous
prostaglandins produced by COX-2 play an important role in the healing of DSS-induced colonic lesions. Caution should be paid to the use of selective
COX-2 inhibitors as well as nonsteroidal anti-inflammatory drugs in patients with
colitis.