Diphenyldisulfide inhibits indomethacin-induced ulcerogenesis in rats.
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.
Institute of Biological Sciences, Syntex Research, Palo Alto, CA 94304.
J M
JM
Young
A J
AJ
Tomolonis
D000818:Animals; D004220:Disulfides / Q000494:pharmacology*; D007213:Indomethacin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007410:Intestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D016859:Lipoxygenase Inhibitors; D008297:Male; D051381:Rats; D014456:Ulcer / Q000139:chemically induced / Q000517:prevention & control
D004220:Disulfides; D016859:Lipoxygenase Inhibitors; C053871:diphenyl disulfide; D007213:Indomethacin