*4.3. Management of ROS by Plasmodium under Steady State: The Antioxidant Machinery*

To match the multiplicity of the sources of ROS, including nitric oxide (Box 1), from both the host and the parasites themselves, malaria parasites have several antioxidant machineries in addition to heme elimination processes, which may be additive or synergistic in ensuring their survival in red blood cells. *Plasmodium* species express antioxidant proteins/enzymes such as superoxide dismutases (SODs), glutathione/glutathione-dependent proteins, thioredoxin/thioredoxin-dependent proteins and thioredoxin reductase, and peroxiredoxins [53,69–71].


**Figure 8.** Major pathways of ROS detoxification. A network of redox cycling cofactors, such as flavin adenine dinucleotide (FADH2) and nicotinamide adenine dinucleotide phosphate (NADPH), aids in the reduction of ROS, avoiding the ultimate and deleterious production of hydroxyl radical •OH from H2O2 by the Fenton reaction in the presence of reduced iron [52]. Abbreviations—SOD: superoxide dismutase, GR: glutathione reductase, GPX: glutathione peroxidases, Prx: peroxiredoxins, TrxR: thioredoxin reductase, GSH: reduced glutathione, GSSG: oxidized glutathione dipeptide, Trxred: reduced thioredoxin, Trxox: oxidized thioredoxin.
