Abstract
Gastric ulcers were produced in male Donryu rats (8-weeks-old) by subserosal injection of 20μl of 20% acetic acid. Five days later, an indomethacin (IND)-filled osmotic pump (OP) was implanted into the dorsal subcutaneous space in the rats and maintained for 2, 3 or 4 weeks. The natural healing of the acetic acid-induced ulcers was significantly (P<0.05) delayed by administration of IND via OP implanted for 4 weeks. Two, 3 and 4 weeks after OP implantation, the plasma IND level was 1.87±0.13, 2.43±0.16 and 0.74±0.26 (μg/ml), respectively, showing that a steady state IND plasma level was maintained for 3 weeks. The gastric mucosal PGE2 levels in rats with ulcers for 3 weeks after implantation of OP were significantly (P<0.05) reduced by IND (IND(-):576.6±83.9 pg/mg, IND(+):355.6±34.7 pg/mg). Repeated administration of enprostil, famotidine and rabeprazole at 25 μg/kg, 100 mg/kg and 10 mg/kg (p.o., b i d), respectively, showed anti-ulcer activity. Teprenone and rebamipide had only slight anti-ulcer activity. These findings indicated that this model of delayed healing of acetic acid ulcers by IND using OP is useful for investigating the anti-ulcer activity of drugs.
