Radical-mediated damage to parasites and erythrocytes in Plasmodium vinckei infected mice after injection of t-butyl hydroperoxide.
Intravenous injection of t-butyl hydroperoxide rapidly killed Plasmodium vinckei in mice, and caused haemolysis. The same dose seemed harmless to unparasitized mice. Many parasites disintegrated inside circulating erythrocytes, so parasite death was not simply a passive consequence of haemolysis. Injection of desferrioxamine, which removes the traces of free iron that promote the dissociation of t-butyl hydroperoxide into radical species, prevented both parasite death and haemolysis. Lipid peroxidation, as measured by accumulation of malonyldialdehyde over 2 h in vitro, occurred in erythrocytes exposed to t-butyl hydroperoxide, and was particularly marked in erythrocytes from parasitized mice. These erythrocytes accumulated appreciable malonyldialdehyde even without exposure to t-butyl hydroperoxide. Desferrioxamine inhibited the accumulation of malonyldialdehyde, but did not prevent depletion of reduced glutathione by t-butyl hydroperoxide. This suggests that t-butyl hydroperoxide damaged parasites and erythrocytes by dissociating into radical species, rather than by decreasing intraerythrocyte anti-oxidant capacity. In earlier experiments we suggested that intraerythrocytic parasite death and haemolysis caused by alloxan were mediated by radical species, and these experiments with t-butyl hydroperoxide add weight to this interpretation. We regard both of these systems as models for macrophage-induced parasite death and host pathology in acute malaria.
D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology; D005260:Female; D005609:Free Radicals; D005978:Glutathione / Q000097:blood; D006461:Hemolysis / Q000187:drug effects; D008288:Malaria / Q000097:blood* / Q000469:parasitology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D010545:Peroxides / Q000494:pharmacology*; D010961:Plasmodium / Q000187:drug effects*; D020122:tert-Butylhydroperoxide
D005609:Free Radicals; D010545:Peroxides; D008315:Malondialdehyde; D020122:tert-Butylhydroperoxide; D005978:Glutathione; D003676:Deferoxamine