Oxygen metabolism in phagocytes of leprotic patients: enhanced endogenous superoxide dismutase activity and hydroxyl radical generation by clofazimine.
We examined the generation of active oxygens (O2-, H2O2, and OH X ) and the superoxide dismutase (SOD) activity of polymorphonuclear leukocytes (PMNs) and monocytes from 14 leprotic patients manifesting a bacillary index above 2.2. Patients with disease of more than 4 years in duration showed significantly enhanced SOD activity and a decrease in O2- and OH X production. The antileprotic agent, clofazimine, significantly increased the generation of OH X in a dose-dependent manner, with a subsequent decrease in H2O2, but had no effect on the SOD activity of the PMNs and monocytes. In medium containing FeSO4 or Fe2+-EDTA, the drug elevated OH X production markedly further. Phagocytic SOD in PMNs and monocytes of leprotic patients was both host and bacillus derived, because the presence of cyanide, to which human-derived cuprozinc SOD is susceptible, did not completely abrogate SOD activity. The difficulty in treating leprosy may be partly ascribable to decreased phagocytic OH X generation, which in leprosy patients is apparently due to the uptake of Hansen bacillus-derived SOD. Clofazimine may be effective in leprosy by chelating Fe2+, with the resultant potentiation of the catalyzing activity of Fe2+ in the Haber-Weiss reaction increasing OH X formation from H2O2.
D000328:Adult; D002991:Clofazimine / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D005296:Ferrous Compounds / Q000494:pharmacology; D005609:Free Radicals; D006801:Humans; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D007918:Leprosy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000032:analysis*
D005296:Ferrous Compounds; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; C020748:ferrous sulfate; D004492:Edetic Acid; D002991:Clofazimine; D013482:Superoxide Dismutase; D010100:Oxygen