Metabolism of dapsone to a hydroxylamine by human neutrophils and mononuclear cells.
Dapsone is an effective anti-inflammatory agent in conditions in which inflammation is mediated by neutrophils. Dapsone also has been associated with agranulocytosis. We found that neutrophils, which had been activated by a phorbol ester or opsonized zymosan, oxidized dapsone to its nitroderivative. It appears as if this is due to oxidation of dapsone by myeloperoxidase to the hydroxylamine, followed by nonenzymatic oxidation of the hydroxylamine to the nitroderivative. The hydroxylamine can be isolated if ascorbic acid is added to the incubations. Monocytes also contain myeloperoxidase and activated mononuclear leukocytes also metabolize dapsone to the hydroxylamine. Dapsone also causes a mononucleosis-like syndrome. The reactive hydroxylamine could be responsible for both the pharmacologic and toxic properties of dapsone.
D000893:Anti-Inflammatory Agents / Q000097:blood*; D001205:Ascorbic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D003622:Dapsone / Q000031:analogs & derivatives / Q000097:blood*; D006801:Humans; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000097:blood*; D007213:Indomethacin / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001386:Azides; D016861:Cyclooxygenase Inhibitors; D006898:Hydroxylamines; C055737:4-nitro-4'-aminodiphenyl sulfone; D019811:Hydroxylamine; D003622:Dapsone; D015054:Zymosan; D002374:Catalase; C018209:4-amino-4'-hydroxylaminodiphenylsulfone; D013755:Tetradecanoylphorbol Acetate; D001205:Ascorbic Acid; D001241:Aspirin; D007213:Indomethacin