Evidence for reactive oxygen intermediates causing hemolysis and parasite death in malaria

A rapid reduction in parasitemia associated with damage to intraerythrocytic parasites was observed in Plasmodium vinckei-infected mice after they had received a single intravenous injection of alloxan. This was not prevented by prior injection of glucose, but was prevented by desferrioxamine or diethyldithiocarbamate. Prior injection of propanol partially blocked the phenomenon. A transient hemolysis was observed in malaria-infected mice, but not in controls, after injection of alloxan. This was also blocked by desferrioxamine, but not by glucose. Both the fall in parasitemia and hemolysis occurred, but less dramatically, when phenylhydrazine or hydrogen peroxide was injected into parasitized mice. Again, the hemolysis was blocked by desferrioxamine. These observations are consistent with the parasite death and hemolysis being mediated by reactive oxygen species, possibly hydroxyl radicals, and have implications for our understanding of hemolysis, endothelial damage, and parasite suppression in acute malaria. Our evidence that malaria parasites are susceptible to free oxygen radicals supports the view that high intraerythrocytic oxidative stress may contribute to the high frequencies in malarial areas of genes for certain erythrocyte-related traits and suggests that some antimalarial drugs may suppress parasites partly through oxidative damage.