Polyamine oxidase-mediated intraerythrocytic killing of Plasmodium falciparum: evidence against the role of reactive oxygen metabolites.
The polyamines spermine and spermidine, in the presence of polyamine oxidase, were shown to be cytotoxic in vitro to various isolates of Plasmodium falciparum. Neither polyamines nor polyamine oxidase alone was cytotoxic. This cytotoxicity was manifested by the degeneration of the parasites into crisis forms and by the inhibition of methionine incorporation by the parasites. Only 2 to 2.5 h of exposure to the reaction mixture (polyamine oxidase, 100 micrograms/ml; spermine, 1 mM) resulted in parasite death. It was shown that ammonia, hydrogen peroxide, and associated reactive oxygen intermediates produced during the oxidation of polyamines were not the cause of the parasite death observed in this system. This suggested that aldehydes or further breakdown products of these, e.g., acrolein (or both), need to be considered as the effector substances of the polyamine oxidase-mediated killing of P. falciparum.
D000818:Animals; D002417:Cattle; D004912:Erythrocytes / Q000502:physiology*; D007700:Kinetics; D008288:Malaria / Q000503:physiopathology; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000097:blood*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development*; D013095:Spermidine / Q000633:toxicity*; D013096:Spermine / Q000633:toxicity*; D000097667:Polyamine Oxidase
D000587:Oxidoreductases Acting on CH-NH Group Donors; D013095:Spermidine; D013096:Spermine; D000097667:Polyamine Oxidase