diamide and Malaria

Normal human erythrocytes, preincubated with the oxidizing agent diamide, did not demonstrate any increased permeability, but showed a significant decrease in their ability to transport the nucleoside adenosine. Diamide appeared to have little effect on glucose permeation in uninfected and Plasmodium falciparum infected cells. The inhibition of adenosine transport in human erythrocytes by diamide pretreatment appeared to be unrelated to the inhibition by the established nucleoside transport inhibitor, nitrobenzylthioinosine (NBMPR). An ID50 for diamide of 0.3 mM was determined for 1 microM adenosine transport in human erythrocytes after preincubation for 45 min at 37 degrees C. However, preincubation of diamide (20 mM, 60 min at 37 degrees C) with Babesia bovis-infected bovine erythrocytes resulted in complete inhibition of the capacity of the parasitised cell to transport adenosine and partial inhibition of glucose permeation. By contrast, diamide was shown to have little or no effect on the new or induced nucleoside permeation site in P. falciparum (trophozoite) infected erythrocytes nor on the glucose transporter in these cells. The results further indicate the differences between the normal human erythrocyte nucleoside and glucose transporters and those new or altered transporters in the membrane of P. falciparum or B. bovis-infected red blood cells.

Topics: Animals; Babesia; Babesiosis; Biological Transport; Cell Membrane Permeability; Diamide; Erythrocytes; Glucose; Humans; Kinetics; Malaria; Nucleosides

Thiol status and growth in normal and glucose-6-phosphate dehydrogenase-deficient human erythrocytes. Experimental Parasitology 57, 239-247. The relationship of the thiol status of the human erythrocyte to the in vitro growth of Plasmodium falciparum in normal and in glucose-6-phosphate dehydrogenase (G6PD)-deficient red cells was investigated. Pretreatment with the thiol-oxidizing agent diamide led to inhibition of growth of P. falciparum in G6PD-deficient cells, but did not affect parasite growth in normal cells. Diamide-treated normal erythrocytes quickly regenerated intracellular glutathione (GSH) and regained normal membrane thiol status, whereas G6PD-deficient cells did not. Parasite invasion and intracellular development were affected under conditions in which intracellular GSH was oxidized to glutathione disulfide and membrane intrachain and interchain disulfides were produced. An altered thiol status in the G6PD-deficient erythrocytes could underlie the selective advantage of G6PD deficiency in the presence of malaria.

Topics: Diamide; Erythrocyte Membrane; Erythrocytes; Glucosephosphate Dehydrogenase Deficiency; Glutathione; Humans; Malaria; Oxidation-Reduction; Plasmodium falciparum