Dehydroepiandrosterone effect on Plasmodium falciparum and its interaction with antimalarial drugs

Dehydroepiandrosterone (DHEA) inhibits glucose 6-phosphate dehydrogenase (G6PDH) of different species and may potentially decrease intracellular glutathione. Therefore, it can have and enhance anti-parasitic action against Plasmodium spp. We evaluated the antiplasmodial activity and the interaction of DHEA with several antimalarial drugs. The inhibitory effect of DHEA on erythrocytic and G6PDH activity and changes in the content of total and reduced gluthatione Plasmodium falciparum content were also evaluated. DHEA showed antiplasmodial activity in vitro, but the potency was low (IC50 118.5 μM). DHEA inhibits G6PDH from healthy erythrocyte and decreases GSH content in both erythrocytes and P. falciparum. DHEA did not synergize or antagonize the antiplasmodial effect of several antimalarial drugs. The most important actions of DHEA were the inhibition of G6PDH activity, and the decrease in both P. falciparum and erythrocyte GSH. Since most of the GSH in Plasmodium spp. infected erythrocytes comes from the parasite itself, it is possible that DHEA analogs could act with higher selectivity, better potency, and might interact synergistically with antimalarials drugs.

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► DHEA showed antiplasmodial activity, but the effect has low potency in vitro.
► DHEA inhibits glucose 6-phosphate dehydrogenase from healthy erythrocyte.
► DHEA decrease P. falciparum and erythrocyte GSH.
► The combination of DHEA with antimalarials drugs showed indifferent interactions.
► It is possible that DHEA analogs could act with higher potency and selectivity.