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Role of pepsin in the development of indomethacin‐induced antral ulceration in the rat
Author(s) -
GAW A. J.,
WILLIAMS L. V.,
SPRAGGS C. F.,
JORDAN C. C.
Publication year - 1995
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.1995.tb00366.x
Subject(s) - pepstatin , pepsin , antrum , medicine , pharmacology , endocrinology , oral administration , chemistry , biochemistry , enzyme , stomach , protease
SUMMARY Aims : To examine the effects of a pepsin inhibitor, pepstatin‐A, a long acting H 2 ‐receptor blocker, loxtidine, exogenous pepsin and exogenous acid against indomethacin‐induced antral ulceration in the rat. Results : Indomethacin (60 mg/kg s.c.) caused antral ulceration in fasted/re‐fed rats over a period of 4 h. Ulceration was prevented in a dose‐dependent manner by treatment with pepstatin‐A (0.1–1 mg.kg hourly) or loxtidine (3 mg/kg) given orally. Acidified methylcellulose (1 mL hourly per os ) enhanced damage and also prevented protection by loxtidine (3 mg/kg per os ). The protection by pepstatin‐A was not altered by treatment with acidified methylcellulose but was reversed by treatment with a 10‐fold excess of pepsin. Conclusion : These studies suggest that mucosal degradation by pepsin, rather than direct damage by luminal acid, was the major factor in the development of indomethacin‐induced antral ulceration in the rat.