Role of lipid peroxidation in dapsone-lnduced hemolytic anemia

David C McMillan, Charles B. Jensen, David J. Jollow

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Abstract

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 concentra-tions of DDS-NOH and examined for evidence of lipid peroxidation using two independent assays: thiobarbituric acid-reactive substances formation and c/s-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 c/s-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 c/s-paranaric acid degradation were significantly increased in red cells treated with hemolytic concentrations of the positive control, phenylhydrazine. These data suggest that lipid peroxi-dation is not involved in the mechanism underlying dapsoneinduced hemolytic anemia.

Original languageEnglish (US)
Pages (from-to)868-876
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume287
Issue number3
StatePublished - Dec 1 1998

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Dapsone
Hemolytic Anemia
Lipid Peroxidation
Thiobarbituric Acid Reactive Substances
Hemolytic Agents
Membrane Proteins
Oxidative Stress
Disulfides
4-amino-4'-hydroxylaminodiphenylsulfone
Hemoglobins
Spleen
Macrophages
Lipids
Membranes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Role of lipid peroxidation in dapsone-lnduced hemolytic anemia. / McMillan, David C; Jensen, Charles B.; Jollow, David J.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 287, No. 3, 01.12.1998, p. 868-876.

Research output: Contribution to journalArticle

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