Role of lipid peroxidation in dapsone-induced hemolytic anemia.
Dapsone hydroxylamine (DDS-NOH) is a direct-acting hemolytic agent responsible for dapsone-induced hemolytic anemia in the rat. The hemolytic activity of DDS-NOH is associated with the formation of disulfide-linked hemoglobin adducts on membrane skeletal proteins. We have postulated that this membrane protein "damage" is a consequence of DDS-NOH-induced oxidative stress within the red cell and that it serves as the trigger for premature removal of injured but intact red cells from the circulation by splenic macrophages. Oxidative stress has also been associated with the induction of lipid peroxidation, and it is possible that direct damage to the lipoidal membrane may play a role in the premature sequestration of the damaged cells in the spleen. To investigate this possibility, rat and human red cells were incubated with hemolytic concentrations of DDS-NOH and examined for evidence of lipid peroxidation using two independent assays: thiobarbituric acid-reactive substances formation and cis-paranaric acid degradation. Phenylhydrazine, which is known to induce lipid peroxidation in red cells, was used as a positive control. The extent of thiobarbituric acid-reactive substances formation and cis-paranaric acid degradation in DDS-NOH-treated rat and human red cells was not significantly different from that in control cells. In contrast, thiobarbituric acid-reactive substances formation and cis-paranaric acid degradation were significantly increased in red cells treated with hemolytic concentrations of the positive control, phenylhydrazine. These data suggest that lipid peroxidation is not involved in the mechanism underlying dapsone-induced hemolytic anemia.
McMillan
D C
DC
Department of Pharmacology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Jensen
C B
CB
Jollow
D J
DJ
D000743:Anemia, Hemolytic / Q000097:blood* / Q000139:chemically induced; D000818:Animals; D003622:Dapsone / Q000031:analogs & derivatives; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D005456:Fluorescent Dyes / Q000032:analysis; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D010659:Phenylhydrazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D005231:Fatty Acids, Unsaturated; D005456:Fluorescent Dyes; D010659:Phenylhydrazines; D017392:Thiobarbituric Acid Reactive Substances; C030299:phenylhydrazine; D003622:Dapsone; C018209:4-amino-4'-hydroxylaminodiphenylsulfone; C013641:parinaric acid