Dapsone-induced hemolytic anemia: Effect of dapsone hydroxylamine on sulfhydryl status, membrane skeletal proteins and morphology of human and rat erythrocytes

D. C. McMillan, J. V. Simson, R. A. Budinsky, D. J. Jollow

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Dapsone hydroxylamine is a direct-acting hemolytic agent responsible for dapsone-induced hemolytic anemia in the rat. In the present study, we compared the responsiveness of rat and human red cells to dapsone hydroxylamine-induced cellular changes. Dapsone hydroxylamine induced a rapid and concentration-dependent loss of erythrocytic reduced glutathione content with a concomitant increase in protein-glutathione mixed disulfide formation in both human and rat red cell suspensions. However, the rate of mixed disulfide formation in human cells was considerably slower than that in rat cells and was preceded by a transient increase in oxidized glutathione (glutathione disulfide) formation. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and immunoblotting analysis of membrane ghosts from human red cells revealed changes in skeletal proteins that in general were similar to those observed with rat cells, including a loss of protein band 2.1 and the appearance of membrane-bound hemoglobin. Notable differences were the resistance to loss of band 4.2 and a considerably higher amount of protein aggregation in human ghosts. Although the morphology of human red cells was altered, the incidence and degree of change were considerably less than those of rat red cells. Furthermore, the concentration of dapsone hydroxylamine required to induce damage in human red cells (175-750 μM) was significantly higher than that required for rat red cells (50-175 μM), suggesting that human cells are probably less sensitive than rat cells to dapsone hydroxyl- amine-induced oxidative damage.

Original languageEnglish (US)
Pages (from-to)540-547
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume274
Issue number1
StatePublished - 1995

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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