RADICAL-MEDIATED DAMAGE TO PARASITES AND ERYTHROCYTES IN PLASMODIUM-VINCKEI INFECTED MICE AFTER INJECTION OF TERT-BUTYL HYDROPEROXIDE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 56  (3) , 524-530
Abstract
I.v. injection of t-butyl hydroperoxide rapidly killed P. vinckei in mice, and caused hemolysis. The same dose seemed harmless to unparasitized mice. Many parasites disintegrated inside circulating erythrocytes, so parasite death was not simply a passive consequence of hemolysis. Injection of desferrioxamine, which removes the traces of free Fe that promote the dissociation of t-butyl hydroperoxide into radical species, prevented both parasite death and hemolysis. 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. Apparently, t-butyl hydroperoxide damaged parasites and erythrocytes by dissociating into radical species, rather than by decreasing intraerythrocyte antioxidant capacity. In earlier experiments it was suggested that intraerythrocytic parasite death and hemolysis caused by alloxan were mediated by radical species, and these experiments with t-butyl hydroperoxide add weight to this interpretation. Both these systems are regarded as models for macrophage-induced parasite death and host pathology in acute malaria.