Antimalarial activity of the ethanol/alcohol oxidase system in vitro

Among other macrophage secretory products, H2O2 plays an important role in the host's defense against malaria (Wozencraft et al., Infect. Immun., 43, 664, (1984]. In our in vitro studies on the human malaria parasite Plasmodium falciparum, hydrogen peroxide was produced by the alcohol oxidase-catalyzed reaction ethanol + O2----acetaldehyde + H2O2 (EC 1.1.3.13). At concentrations of 8.7 mM (= 0.5%) ethanol and 0.1 U alcohol oxidase per ml culture, more than 95% of the parasites were irreversibly damaged. Acetaldehyde was found to be parasiticidal per se--probably by releasing immature forms of P. falciparum from erythrocytes--but CH3CHO concentrations as high as 90 mM were required for complete elimination of the parasites. Ethanol (less than 20 mM) or alcohol oxidase alone had no significant effect on parasite viability. As discussed, the ethanol/alcohol oxidase system might be of interest as a potential chemotherapeutic principle, especially since metabolism and pharmacology of the substrates and products are well understood.