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Lack of small intestinal ulcerogenecity of nitric oxide‐releasing indomethacin, NCX‐530, in rats
Author(s) -
Mizoguchi H.,
Hase S.,
Tanaka A.,
Takeuchi K.
Publication year - 2001
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 - 10.1046/j.1365-2036.2001.00916.x
Subject(s) - nitric oxide , nitric oxide synthase , mucus , ileum , small intestine , myeloperoxidase , jejunum , medicine , pharmacology , cyclooxygenase , prostaglandin , endocrinology , chemistry , biochemistry , inflammation , enzyme , biology , ecology
Aim: To evaluate the intestinal ulcerogenic property of nitric oxide‐releasing indomethacin (NCX‐530) in the rat, in comparison with indomethacin. Methods: Animals were given indomethacin or NCX‐530 subcutaneously and killed 24 h later for macroscopic examination of the small intestine. Results: A single administration of indomethacin (10 mg/kg) provoked damage, mainly in the jejunum and ileum, accompanied by an increase in myeloperoxidase and inducible nitric oxide synthase activities as well as bacterial translocation. NCX‐530 at an equimolar dose (14.2 mg/kg) caused no gross damage in the small intestine, nor any significant change in inducible nitric oxide synthase and myeloperoxidase activities or bacterial translocation. NOR‐3, the nitric oxide donor (6.0 mg/kg), when administered subcutaneously together with indomethacin, significantly prevented the occurrence of intestinal lesions and other mucosal changes. Indomethacin reduced mucus and fluid secretions in the small intestine, while both NCX‐530 and NOR‐3 enhanced these secretions. NCX‐530 reduced the mucosal prostaglandin E2 contents and exhibited an anti‐inflammatory action against carrageenan‐induced paw oedema, with equal effectiveness to indomethacin. Conclusion: NCX‐530 does not cause intestinal damage, despite inhibiting cyclooxygenase activity. The reduced intestinal toxicity of NCX‐530 may be attributable to inhibition of enterobacterial translocation, partly by increasing the mucus and fluid secretions mediated by nitric oxide released from this compound.