Amino acid supplementation confers protection to red blood cells prior to Plasmodium falciparum bystander stress

Malaria is a highly oxidative parasitic disease in which anemia is the most common clinical symptom. A major contributor to malarial anemia pathogenesis is the destruction of bystander, uninfected red blood cells. Metabolic fluctuations are known to occur in the plasma of individuals with acute malaria, emphasizing the role of metabolic changes in disease progression and severity. Here, we report that conditioned media from Plasmodium falciparum culture induces oxidative stress in healthy uninfected RBCs. Additionally, we show the benefit of amino acid pre-exposure for RBCs and how this pre-treatment intrinsically prepares RBCs to mitigate oxidative stress. Key pointsO_LIIntracellular ROS is acquired in red blood cells incubated with Plasmodium falciparum conditioned media C_LIO_LIGlutamine, cysteine, and glycine amino acid supplementation increased glutathione biosynthesis and reduced ROS levels in stressed RBCs C_LI