ANTIMALARIAL ACTIVITY OF THE ETHANOL ALCOHOL OXIDASE SYSTEM INVITRO

Among other macrophage secretory products, H2O2 plays an important role in the host's defense against malaria (Wozencrafl 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 → acetaldehydc + 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 90mM were required for complete elimination of the parasites. Ethanol (< 20mM) or alcohol oxidase alone had no significant effect on parasite viability. As discussed, the elhanol/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. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.