*3.2. Lipid Peroxidation*

Lipids are prone to attacks from reactive species, resulting in their oxidation and the formation of lipid peroxides [25] (Figure 3). This leads to cellular dysfunction, especially as lipids are major components of cell membranes. In *Plasmodium*, artemisinin and its derivatives accumulate in neutral lipid bodies, especially in the digestive vacuole, where they can trigger oxidative damage after their heme–iron activation [26], via a lipid peroxidation process that, once initiated, is propagated by autocatalysis to free fatty

acids [26]. This oxidative damage leads to a loss of Plasmodium membrane integrity and, consequently, parasite death. Moreover, tetraoxanes oxidatively damage phospholipids more than artemisinin [27], which may account for the differential antimalarial effect of these endoperoxides.

**Figure 3.** Lipid peroxidation. Lipid peroxidation occurs in three phases: initiation (A), propagation (B), and termination (C). Malondialdehyde (MDA) is a biomarker of lipid peroxidation in living cells. Among lipids, polyunsaturated fatty acids (PUFAs) are the most vulnerable to lipid peroxidation. COOH = carboxyl group, OOH = hydroperoxyl.
