1921
Volume 21, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645
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Abstract

Abstract

Methemoglobinemia is an important side effect of dapsone (4,4′-diaminodiphenyl sulfone; DDS) therapy. Previous workers had shown a correlation between methemoglobin formation and time of incubation of DDS in a system involving rat liver microsomes and human red cells (RBC). N-Oxidation of ring C labelled DDS by rat liver microsomes was studied both in the presence and absence of RBC. Evidence is presented that in vitro DDS is metabolized to the monohydroxylamine of DDS (DDS-NOH), and maybe to the nitroso-(DDS-NO) and azoxy- (azoxy-DDS) analogues of DDS. The latter compounds could also arise from non-microsomal oxidation of DDS-NOH. Specific isotope dilution procedures were employed to measure the N-oxidation of DDS. These involved conversion to azoxy-DDS or the formation of the pentocyanamine ferroate complex of DDS-NOH (and/or DDS-NO). The extent of total N-oxidation of DDS was always less when experiments were carried out in the presence of RBC than in their absence. This suggests that DDS-NOH is enzymatically reduced by RBC. Like other microsomal oxidations, N-oxidation of DDS was inhibited by SKF-525A. Our studies indicate that DDS-NOH (and/or DDS-NO) is the cause of the methemoglobinemia observed in dapsone therapy.

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/content/journals/10.4269/ajtmh.1972.21.322
1972-05-01
2017-09-24
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http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.1972.21.322
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  • Accepted : 23 Jan 1972

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