A new ulcer model, "unhealed gastric ulcers", induced by chronic treatment with indomethacin in rats with acetic acid ulcers.
The healing of experimental gastric ulcers induced in rats is consistently delayed upon chronic treatment with indomethacin. This study was designed to examine both the fate of such delayed ulcers and the effects of various antiulcer drugs on the delayed ulcers. Four-week treatment with indomethacin significantly delayed the healing of acetic acid ulcers. Such ulcers remained unhealed for up to 12 weeks after cessation of indomethacin treatment, and were thus designated as "unhealed ulcers". Two-week administration of sucralfate, cimetidine or omeprazole significantly reduced the ulcerated area, yet aluminum hydroxide had little or no effect. Four-week administration of sucralfate also extensively reduced the size of the "unhealed ulcers", yet aluminum hydroxide, cimetidine and omeprazole had an insignificant effect on "unhealed ulcers". In the 2 and 4 week sucralfate-treated group, the pH of the gastric contents was 4.0 vs. 1.7 and 4.5 vs. 2.1 in the control groups, respectively. Gastric acid secretion was extensively inhibited by cimetidine and omeprazole. It is concluded that prolonged indomethacin treatment results in the development of "unhealed ulcers" and that only sucralfate has a beneficial effect on such ulcers, irrespective of the length of the treatment.
Amagase
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Yamashima, Japan.
Okabe
S
S
D019342:Acetic Acid; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005744:Gastric Acid / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D014945:Wound Healing / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D016861:Cyclooxygenase Inhibitors; D019342:Acetic Acid; D007213:Indomethacin