Dissociation of the inhibitory effect of dapsone on the generation of oxygen intermediates--in comparison with that of colchicine and various scavengers.
4,4'-Diaminodiphenyl sulfone (dapsone, DDS) is highly effective in dermatitis herpetiformis and immune complex disease in which polymorphonuclear leukocytes (PMN) play an important role. We studied the dose-response effect of DDS (10-1 mM) on the generation of oxygen intermediates (OI:O2-, H2O2, OH.) and chemiluminescence using PMN and the xanthine-xanthine oxidase system. The effect of colchicine and five oxygen radical scavengers on OI production in both systems was also examined and compared with that of DDS. We found that, except for O2- generation, which was slightly enhanced, DDS decreased the levels of OI measured as effectively as scavengers. Scavengers also capable of degrading OH. and 1O2 markedly reduced the levels of OH. and chemiluminescence while slightly increasing the level of O2-. Therefore, DDS was considered to exert effects similar to H2O2, and OH. and 1O2 scavengers. Colchicine did not decrease OI values produced in the xanthine-xanthine oxidase system but affected PMN-mediated OI generation, possibly by its cytoxic effect. Our results suggest that DDS, in contrast to colchicine brings about rapid clinical improvement in PMN-mediated autooxidative disorders by quenching reactive OI such as H2O2, OH. and chemiluminescence.
D003078:Colchicine / Q000494:pharmacology*; D003622:Dapsone / Q000494:pharmacology*; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D005609:Free Radicals; D006878:Hydroxides; D013481:Superoxides; D017665:Hydroxyl Radical; D003622:Dapsone; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D010100:Oxygen; D003078:Colchicine