David C. McMillan

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Primaquine is an important antimalarial agent because of its activity against exoerythrocytic forms of Plasmodium spp. However, methemoglobinemia and hemolytic anemia are dose-limiting side effects of primaquine therapy that limit its efficacy. These hemotoxicities are thought to be mediated by metabolites; however, the identity of the toxic species has(More)
Previous studies have shown that incubation of rat red blood cells in vitro with phenylhydroxylamine (50-300 microM) induces rapid splenic sequestration of the red cells on reintroduction to isologous rats. EPR and the spin trapping agent, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), were utilized to determine if free radical species could be identified under(More)
Methemoglobinemia produced by exposure to the herbicide propanil (3,4-dichloropropionanilide) is thought to be mediated by toxic metabolites formed during the hepatic clearance of the parent compound. We examined the metabolism of propanil and 3,4-dichloroaniline in rat liver microsomes to identify metabolites that may be involved in propanil-induced(More)
Lipid peroxidation and the accompanying translocation of phosphatidylserine (PS) from the inner to the outer leaflet of the lipid bilayer have recently been identified as key components of a signaling pathway for phagocytosis of apoptotic cells by macrophages. Drug-induced hemolytic anemia has long been known to be caused by an accelerated uptake of damaged(More)
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(More)
Favism is an acute hemolytic anemia known to occur in susceptible individuals who ingest fava beans. Susceptibility to favism is conferred by a genetic deficiency in erythrocytic glucose-6-phosphate dehydrogenase (G6PD) activity. Although the fava bean pyrimidine aglycones, divicine and isouramil, have been implicated in the onset of favism in humans, the(More)
The hemolytic activity of dapsone is well known to reside in its N-hydroxylamine metabolites. Addition of dapsone hydroxylamine (DDS-NOH) to red cell suspensions causes damage such that when reintroduced into the circulation of isologous rats, the injured cells are rapidly removed by the spleen. Hemolytic activity is associated with the extensive formation(More)
Previous studies have shown that 6-methoxy-8-hydroxylaminoquinoline (MAQ-NOH), an N-hydroxy metabolite of the antimalarial drug, primaquine, is a direct-acting hemolytic agent in rats. To investigate the mechanism underlying this hemolytic activity, the effects of hemotoxic concentrations of MAQ-NOH on rat erythrocyte sulfhydryl status, membrane lipids,(More)
BACKGROUND Trichloroethylene (TCE) is a suspected human carcinogen and a common groundwater contaminant. Chloral hydrate (CH) is the major metabolite of TCE formed in the liver by cytochrome P450 2E1. CH is metabolized to the hepatocarcinogen trichloroacetate (TCA) by aldehyde dehydrogenase (ALDH) and to the noncarcinogenic metabolite trichloroethanol(More)
Favism is an acute anemic crisis that can occur in susceptible individuals who ingest fava beans. The fava bean pyrimidine aglycone divicine has been identified as a hemotoxic constituent; however, its mechanism of toxicity remains unknown. We have shown recently that divicine can induce a favic-like response in rats and that divicine is directly toxic to(More)