Toxicity of certain products of lipid peroxidation to the human malaria parasite Plasmodium falciparum

Aldehydes generated during radical-induced lipid peroxidation, in particular 4-hydroxynonenal, are known to inhibit growth of certain cells. To extend our arguments that free radicals might be involved in the host response against malaria parasites we tested 26 carbonyls ( n-alkanals, C 6-C 11; 2-alkenals, C 3-C 9; 2, 4-alkadienals, C 7, C 9, C 10; 4-OH-2-alkenals, C 6, C 8, C 8; 2-alkanones, C 3-C 9; and malonyldialdehyde) against Plasmodiwn falciparum in vitro. We had previously detected many of these substances in oxidant-stressed, malaria-infected erythrocytes. Three 2,4-alkadienals (C 7, C 9 and C 10) and three 4-OH-2-alkenals (C 6, C 8 and C 9), at 20–100 μM concentrations, markedly inhibited incorporation of [ 3H]-hypoxanthine by P. falciparum. Acrolein had low effect, and none of the other compounds (12 aldehydes and 7 ketones) were active at concentrations up to 100 μM. Malonyldialdehyde was without effect at concentrations up to 450 μM. The aldehydes found to be inhibitory against P. falciparum could contribute to both the non-antibody host responses against this parasite and the antimalarial effects of radical-generating compounds such as t-butyl hydroperoxide, hydrogen peroxide, alloxan, isouramil, divicine and primaquine