In:
American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 290, No. 4 ( 2006-04), p. G747-G756
Abstract:
Traditional NSAIDs, selective cyclooxygenase (COX)-2 inhibitors, and inhibitors of nitric oxide synthase (NOS) impair the healing of preexisting gastric ulcers. However, the role of COX-1 (with or without impairment of COX-2) and the interaction between COX and NOS isoforms during healing are less clear. Thus we investigated healing and regulation of COX and NOS isoforms during ulcer healing in COX-1 and COX-2 deficiency and inhibition mouse models. In this study, female wild-type COX-1 −/− and COX-2 −/− mice with gastric ulcers induced by cryoprobe were treated intragastrically with vehicle, selective COX-1 (SC-560), COX-2 (celecoxib, rofecoxib, and valdedoxib), and unselective COX (piroxicam) inhibitors. Ulcer healing parameters, mRNA expression, and activity of COX and NOS were quantified. Gene disruption or inhibition of COX-1 did not impair ulcer healing. In contrast, COX-2 gene disruption and COX-2 inhibitors moderately impaired wound healing. More severe healing impairment was found in dual (SC-560 + rofecoxib) and unselective (piroxicam) COX inhibition and combined COX impairment (in COX-1 −/− mice with COX-2 inhibition and COX-2 −/− mice with COX-1 inhibition). In the ulcerated repair tissue, COX-2 mRNA in COX-1 −/− mice, COX-1 mRNA in COX-2 −/− mice, and, remarkably, NOS-2 and NOS-3 mRNA in COX-impaired mice were more upregulated than in wild-type mice. This study demonstrates that COX-2 is a key mediator in gastric wound healing. In contrast, COX-1 has no significant role in healing when COX-2 is unimpaired but becomes important when COX-2 is impaired. As counterregulatory mechanisms, mRNA of COX and NOS isoforms were increased during healing in COX-impaired mice.
Type of Medium:
Online Resource
ISSN:
0193-1857
,
1522-1547
DOI:
10.1152/ajpgi.00416.2005
Language:
English
Publisher:
American Physiological Society
Publication Date:
2006
detail.hit.zdb_id:
1477329-6
SSG:
12
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