Fig. 1

a. Illustration of glycolytic metabolic fluxes during normal conditions. Previous studies indicate that the PPP uses 30 % of the glucose consumed by the RBC [43]. b. Illustration of glycolytic metabolic fluxes during increased PPP flux resulting from methylene blue. The response of the RBC PPP to methylene blue has been widely used to demonstrate the presence of PPP in RBC [44]. c. Glucose consumption of Plasmodium berghei ANKA (PbA) infected RBCs, uninfected RBCs and free parasites. Parasitaemia was 10 % of the infected RBC. Glucose utilization of infected RBCs was 35 times higher than uninfected RBCs. Free parasites accounted for the increased in glucose consumption. Glucose consumption during increased PPP flux with methylene blue (MB, 5 mM) augmented glucose utilization of uninfected RBCs by 80 % compared to control conditions. Infected RBCs increased PPP flux in response to MB by more than 120 %, and the free parasite increased PPP flux in response to MB by 100 %. Therefore, the parasite and infected RBCs have large capacity to deal with oxidative stress, and the uninfected RBCs to preserve reduced Hb and GSH. d. Glucose consumption of Plasmodium berghei ANKA infected RBCs, uninfected RBCs and free parasites treated with 20 μM RRx-001. RRx-001 reduced glucose utilization of uninfected, infected RBCs and parasites. RRx-001 also prevented the drastic increase in glucose consumption during of increased PPP flux with MB (5 mM). Although, MB still increased the glucose utilization of RRx-001 treated uninfected RBCs by 35 %, in the infected RBCs by 55 %, and in the free parasite by 80 %, respectively. Therefore, RRx-001 reduced the capacity of parasites, infected RBCs and uninfected RBCs to deal with oxidative stress, and to preserve reduced Hb and GSH