Artemisinin derivatives exert rapid antimalarial activity primarily through iron-dependent
radical generation and oxidative damage within Plasmodium parasites. Concurrent administration
of antioxidant supplements during malaria therapy is common in endemic regions,
yet their mechanistic impact on artemisinin efficacy remains poorly understood. This study
investigates the redox- and iron-mediated mechanisms underlying the interaction between
dihydroartemisinin (DHA) and ascorbic acid (AA) in a Plasmodium berghei-infected murine
model. Biochemical analyses of oxidative stress markers, antioxidant enzyme systems,
labile iron pools, and heme metabolism were conducted alongside parasitemia and hepatic
injury assessment. The findings demonstrate that AA significantly attenuates DHA-induced
oxidative stress and disrupts iron-dependent radical formation, leading to reduced parasite
clearance and altered hepatic redox balance. These results provide mechanistic evidence that
antioxidant supplementation can compromise artemisinin efficacy and highlight the need for
evidence-based guidance regarding adjunctive vitamin use during antimalarial therapy.
