Antiangiogenic effect of a highly selective cyclooxygenase-2 inhibitor on gastric ulcer healing in rats

Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong.
Toxicology and Applied Pharmacology (Impact Factor: 3.71). 09/2002; 183(1):41-5. DOI: 10.1006/taap.2002.9457
Source: PubMed

ABSTRACT Selective cyclooxygenase-2 (COX-2) inhibitors have been shown to produce fewer gastrointestinal adverse reactions when compared with conventional nonselective nonsteroidal anti-inflammatory drugs and they suppress angiogenesis in tumors. The purpose of the present study was to investigate the effects of highly selective COX-2 inhibitor on angiogenesis and protein expression of angiogenic factor during gastric ulcer healing. Gastric ulcers were induced in male Sprague-Dawley rats by a luminal application of acetic acid solution. Rofecoxib, a selective COX-2 inhibitor, was administered at a dose of 10 mg/kg/day by gastric intubation for 14 successive days. The ulcer size was measured at different time intervals after ulcer induction. The microvessels that were immunohistologically positive for von Willebrand factor within the ulcer bed were counted. The protein levels of basic fibroblast growth factor (bFGF) and concentration of prostaglandin E(2) (PGE(2)) in the ulcer tissues were analyzed with Western blotting and immunoassay methods, respectively. The results demonstrated that rofecoxib treatment significantly increased the ulcer size at days 6, 10, and 15. It decreased the number of microvessels, bFGF protein expression, and PGE(2) level in the ulcer base at day 6. The findings that highly selective COX-2 inhibitor delayed ulcer healing in rats and impaired angiogenesis in the ulcer base raise cautions regarding the use of COX-2 inhibitors in patients with gastric ulcers.

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    • "Since growthpromoting actions and angiogenesis are not only essential for tumor growth but also play a pivotal role in wound healing, selective cyclooxygenase-2 inhibitors may suppress these activities in gastric ulcer tissues and delay the healing process. Exogenous growth factors could enhance the healing of acetic-acid-induced gastric ulcers in rats and of NSAID-related ulcers in patients (Pohle et al., 1999; Konturek et al., 2001; Guo et al., 2002). However, limited information is available regarding whether NSAIDs, especially the cyclooxygenase-2 selective category, have any effect on the expression of growth factors and associated processes. "
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