02255nas a2200361 4500000000100000008004100001260001300042653001000055653001600065653001600081653001100097653002200108653001800130653001100148653001500159653002100174653001200195653000900207653001600216653001100232653001500243653002500258100001100283700001300294700001400307700001200321245015600333856007800489300001100567490000700578520129400585022001401879 1984 d c1984 Nov10aAdult10aClofazimine10aEdetic Acid10aFemale10aFerrous Compounds10aFree Radicals10aHumans10aHydroxides10aHydroxyl Radical10aleprosy10aMale10aMiddle Aged10aOxygen10aPhagocytes10aSuperoxide Dismutase1 aNiwa Y1 aSakane T1 aMiyachi Y1 aOzaki M00aOxygen metabolism in phagocytes of leprotic patients: enhanced endogenous superoxide dismutase activity and hydroxyl radical generation by clofazimine. uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC271453/pdf/jcm00124-0039.pdf a837-420 v203 a
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.
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