Cyclo-oxygenase-2 inhibitors suppress epithelial cell kinetics and delay gastric wound healing in rats

Citation
Wh. Sun et al., Cyclo-oxygenase-2 inhibitors suppress epithelial cell kinetics and delay gastric wound healing in rats, J GASTR HEP, 15(7), 2000, pp. 752-761
Citations number
43
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
ISSN journal
08159319 → ACNP
Volume
15
Issue
7
Year of publication
2000
Pages
752 - 761
Database
ISI
SICI code
0815-9319(200007)15:7<752:CISECK>2.0.ZU;2-9
Abstract
Background and Aims: The present study examined the effects of NS-398, a sp ecific cyclo-oxygenase-2 inhibitor, on gastric mucosal cell kinetics and ga stric wound healing following acid-induced injury. Methods: Male Sprague-Dawley rats were fasted for 24 h and then 0.6 mol/L h ydrochloric acid (HCl; 1 mL) was administered into the stomach; NS-398 or i ndomethacin was administered to the animals 10 min after the acid. Levels o f constitutive cyclo-oxygenase (COX-1) and mitogen-inducible cyclo-oxygenas e (COX-2) in the gastric mucosa were analysed using western blotting and im munohistochemical staining. The grade of the lesion was assessed using plan imetry and histological examination, including immunohistochemistry for pro liferating cell nuclear antigen (PCNA). Results: Although there was strong expression of COX-1, there was minimal e xpression of COX-2 in the gastric mucosa. Expression of COX-2 was enhanced mainly in surface epithelial cells and neck cells following HCl administrat ion. Gastric mucosal ulcers and erosions healed within 48 h, during which t ime the proliferative zone expanded in the control animals. Indomethacin an d NS-398 suppressed the expansion of the proliferative zone and delayed the healing of the gastric injury. Conclusion: The present study demonstrated that cyclo-oxygenase-2 inhibitor s delay gastric wound healing by suppressing expansion of the mucosal proli ferative zone. These results provide evidence that cyclo-oxygenase-2 has an important role in gastric mucosal regeneration. (C) 2000 Blackwell Science Asia Pty Ltd.