RT Journal Article
SR Electronic
T1 Dapsone-induced hemolytic anemia: role of glucose-6-phosphate dehydrogenase in the hemolytic response of rat erythrocytes to N-hydroxydapsone.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 870
OP 877
VO 273
IS 2
A1 S Grossman
A1 R Budinsky
A1 D Jollow
YR 1995
UL http://jpet.aspetjournals.org/content/273/2/870.abstract
AB Individuals deficient in erythrocytic glucose-6-phosphate dehydrogenase (G6PD) show about a 2-fold increase in sensitivity toward dapsone-induced hemolytic anemia. Rat studies have shown that the hemolytic activity of dapsone resides in its N-hydroxy metabolites; exposure of rat red cells to N-hydroxy-dapsone in vitro followed by readministration to isologous rats results in premature splenic sequestration of the damaged cells. This study examines the ability of the steroid, epiandrosterone, to inhibit rat red cell G6PD and the effect of such inhibition on the susceptibility of rat red cells to N-hydroxydapsone hemolytic activity. Epiandrosterone was found to inhibit rat red cell G6PD uncompetitively and to suppress red cell hexose monophosphate shunt activity by more than 95%. Epiandrosterone suppression of rat red cell G6PD activity resulted in about a 2-fold increase in sensitivity of the rat cells to N-hydroxydapsone hemolytic activity, and a modest but significant increase in depletion of red cell glutathione. In contrast, suppression of rat red cell catalase activity by aminotriazole had no effect on the hemotoxicity of N-hydroxydapsone. Epiandrosterone appears to be a useful tool to explore the mechanism by which G6PD deficiency enhances susceptibility to hemolytic drugs.