Selenium-Independent Glutathione Peroxidase in Malaria Parasites

Abstract

Inherited and/or acquired alterations of red blood cell metabolism, like glucose-6-phosphate dehydrogenase- or vitamin E deficiency, which influence peroxide metabolism, inhibit the regular intracellular development of the malaria parasite. Many antimalarials are peroxides (e.g., t-butyle-hydroperoxide/t-BHP, qinghaosu/QHS) or radical generators (e.g., primaquine, isouramil). Reactive oxygen species are thought to belong to the main mediators in the unspecific immune reactions against intracellular protozoan parasites (reviewed by Clark et al. 1986; Roth et al. 1986). It is still unknown as to whether the parasite, the host erythrocyte, or both are responsible for the increased susceptibility to oxidative damage and whether the parasite participates in the redox cycle capacity of the host cell. The susceptibility of the normal red blood cell, the parasitized erythrocyte or the parasite to oxidative damage depends on the individual antioxidant capacity. The relation of Oxidative Stress Versus Antioxidant Capacity (OSVAC) is very decisive for either the survival or non-survival of malaria parasites or infected erythrocytes. An increase in the oxidant stress and/or a decrease in the antioxidant capacity (e g, inhibition of the redox cycle enzymes, vitamin E or vitamin C deficiency) disturbs the critical OSVAC balance within the infected cell and might thus lead to a more or less selective destruction of the parasite or the host RBC. Because the parasitized red blood cell is a multicompartment system, it is very difficult to distinguish between the metabolic activities of host and guest cells. In the course of its intracellular multiplication, the parasite degrades up to 75% of host's cell stroma and as such the metabolic capacity of the residual erythrocytes becomes more and more labile. The aim of these investigations was to determine whether malaria parasites depend on the host cell's redox cycle and whether OSVAC of host and guest cells are of different qualities.

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