Effect of NC-1300-O-3 on healing of acetic acid-induced gastric ulcers in rats.
We examined the effect of NC-1300-O-3 on the healing of acetic acid-induced gastric ulcers in male Donryu rats. NC-1300-O-3, administered orally once daily for 2, 4 or 8 weeks after ulceration, significantly accelerated the spontaneous healing of both fresh and unhealed ulcers (induced by pretreatment with indomethacin). The delay in ulcer healing caused by indomethacin was markedly prevented by concurrent administration of NC-1300-O-3 once daily for 4 weeks in a dose-related manner. A bolus administration of NC-1300-O-3 to rats with 5-day-old ulcers potently and persistently (> 48 hr) inhibited both the basal and histamine-stimulated gastric secretion. However, the potency and duration of the anti-secretory activity of the compound, with or without indomethacin, gradually decreased with the period of treatment. After an 8-week treatment with NC-1300-O-3 alone, the volume of the gastric contents was markedly increased, resulting in an increased acid output. Administration of the compound together with indomethacin for 8 weeks resulted in a significant increase in the volume, no change in acid output and a significant increase in the pH. The spontaneous or delayed healing of gastric ulcers induced 4 weeks after pretreatment with NC-1300-O-3 was also significantly enhanced or prevented with NC-1300-O-3, with a weakened antisecretory activity. Therefore, NC-1300-O-3 seems to promote ulcer healing or prevents delayed healing by its potential antisecretory and/or ulcer-healing activities.
Okabe
S
S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Takagi
K
K
Inoue
K
K
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000085:Acetates; D019342:Acetic Acid; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D006632:Histamine / Q000494:pharmacology; D007213:Indomethacin; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000085:Acetates; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; C048733:2-((2-dimethylaminobenzyl)sulfinyl)benzimidazole; D006632:Histamine; D009853:Omeprazole; D019342:Acetic Acid; D007213:Indomethacin