ISSN:
1365-2036
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
To evaluate the intestinal ulcerogenic property of nitric oxide-releasing indomethacin (NCX-530) in the rat, in comparison with indomethacin.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Animals were given indomethacin or NCX-530 subcutaneously and killed 24 h later for macroscopic examination of the small intestine.〈section xml:id="abs1-3"〉〈title type="main"〉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.〈section xml:id="abs1-4"〉〈title type="main"〉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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1365-2036.2001.00916.x
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