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

• Published in: Journal of gastroenterology and hepatology 2000-07, Vol.15 (7), p.752-761
• Main Authors: Sun, Wei-Hao, Tsuji, Shingo, Tsujii, Masahiko, Gunawan, Edhi S, Sawaoka, Hitoshi, Kawai, Naoki, Iijima, Hideki, Kimura, Arata, Kakiuchi, Yoshimi, Yasumaru, Masakazu, Sasaki, Yutaka, Kawano, Sunao, Hori, Masatsugu
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Division - drug effects; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Epithelial Cells - cytology; Epithelial Cells - drug effects; gastric damage; Gastric Mucosa - drug effects; Gastric Mucosa - metabolism; General pharmacology; Indomethacin - pharmacology; Isoenzymes - biosynthesis; Male; Medical sciences; Membrane Proteins; Nitrobenzenes - pharmacology; non-steroidal anti-inflammatory drug; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; prostaglandin endoperoxide synthase; Prostaglandin-Endoperoxide Synthases - biosynthesis; Rats; Rats, Sprague-Dawley; stomach; Stomach - surgery; Sulfonamides - pharmacology; Wound Healing - drug effects
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1046/j.1440-1746.2000.02242.x

Background and Aims : The present study examined the effects of NS‐398, a specific cyclo‐oxygenase‐2 inhibitor, on gastric mucosal cell kinetics and gastric wound healing following acid‐induced injury. Methods : Male Sprague‐Dawley rats were fasted for 24 h and then 0.6 mol/L hydrochloric acid (HCl; 1 mL) was administered into the stomach; NS‐398 or indomethacin was administered to the animals 10 min after the acid. Levels of constitutive cyclo‐oxygenase (COX‐1) and mitogen‐inducible cyclo‐oxygenase (COX‐2) in the gastric mucosa were analysed using western blotting and immunohistochemical staining. The grade of the lesion was assessed using planimetry and histological examination, including immunohistochemistry for proliferating cell nuclear antigen (PCNA). Results : Although there was strong expression of COX‐1, there was minimal expression of COX‐2 in the gastric mucosa. Expression of COX‐2 was enhanced mainly in surface epithelial cells and neck cells following HCl administration. Gastric mucosal ulcers and erosions healed within 48 h, during which time the proliferative zone expanded in the control animals. Indomethacin and 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 inhibitors delay gastric wound healing by suppressing expansion of the mucosal proliferative zone. These results provide evidence that cyclo‐oxygenase‐2 has an important role in gastric mucosal regeneration.