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

Abstract

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.

Human monocytes cultured with and without interferon‐gamma inhibit Plasmodium falciparum parasite growth in vitro via secretion of reactive nitrogen intermediates

“…Previous studies have suggested both oxygen and oxygen dependent factors as being responsible for parasite killing (Ockenhouse et al 1984, Rockett et al 1991, Clark & Hunt 1983. The role for nitric oxide in killing of liver-, asexual-and gametocytic stages of P .…”

The production of reactive oxygen species in mice infected or immunized with Plasmodium berghei

“…Binding of phagocytes with target cells initiates oxidative metabolism which results in increased oxygen consumption, higher hexose monophosphate shunt activity and generation of highly reactive oxidizing substances such as superoxide anions (Oi), hydrogen peroxide, hydroxyl radicals (OH -) and singlet oxygen (O;), which are involved in the lysis of a variety of target cells (Babior 1978). Since a group of Australian scientists demonstrated that injection of alloxan, a drug that generates oxygen radicals, into mice infected with Plasmodium tiinckei causes a rapid reduction in parasitaemia, accompanied by parasite damage and haemolysis (Clark & Hunt 1983), evidence has accumulated that several species of rodent and human malaria parasites are susceptible to reactive oxygen Correspondence: Dr M. Li, Department of Malaria Research, The First Medical College of PLA. Guangzhou (Canton).…”

Generation of Reactive Oxygen Radicals by Human Phagocytic Cells Activated by Plasmodium falciparum

“…The involvement of oxygen radicals, generated by phagocytic cells [24. 34], or by compounds such as alloxan [6], t-butyl hydroperoxide [7] or glucose-glucose oxidase and xanthine-xanthine oxidase systems [8] in causing intra-erythrocytic death of malaria parasites is well documented. PMN and monocytes.…”