Diphenyldisulfide inhibits indomethacin-induced ulcerogenesis in rats |
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Authors: | J M Young A J Tomolonis |
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Institution: | (1) Institute of Biological Sciences, Syntex Research R7-201, 3401 Hillview Avenue, 94304 Palo Alto, CA, USA |
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Abstract: | Indomethacin was administered subcutaneously to rats, 4 mg/kg/day for 4 consecutive days in order to produce erosions of the small intestine which were scored at necropsy on day 5. Orally administered phenidone (up to 250 mg/kg/day), a mixed cycloocygenase-lipoxygenase inhibitor, failed to produce intestinal erosions, but tended to exacerbate indomethacin-induced erosions. A 5-LO inhibitor, diphenyldisulfide, provided significant protection at 10–100 mg/kg when given orally to indomethacin-treated rats. Sulfasalazine, auranofin and cyproheptadine, but not cimetidine, also protected, suggesting a role for mast cell activation and leukotriene generation in indomethacin-induced ulcerogenesis. |
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