The role of antioxidants treatment on the pathogenesis of malarial infections: a review

Abstract

Oxidative damage is one of the most important pathological consequences of malarial infections. It affects vital organs of the body manifesting in changes such as splenomegaly, hepatomegaly, endothelial and cognitive damages. The currently used antimalarials often leave traces of these damages after therapy, as evident in memory impairment after cerebral malaria. Hence, some research investigations have focused attention on the use of antioxidants, alone or in combination with antimalarials, as a viable therapeutic strategy aimed at alleviating plasmodium-induced oxidative stress and its associated complications. However, the practical application of this approach often yields conflicting outcomes because some antimalarials specifically act via induction of oxidative stress. This article critically reviews most of the studies conducted on the potential role of antioxidant therapy in malarial infections. The most frequently investigated antioxidants are vitamins C and E, N-acetylcystein, folate and desferroxamine. Some of the investigations measured the effects of direct administration of the antioxidants on the plasmodium parasites while others performed an adjunctive therapy with standard antimalarials. The therapeutic application of each of the antioxidants in malaria management depends on the targeted aspect of malarial pathology. It is hoped that this article will provide an informed basis for future research activities on the therapeutic role of antioxidants on malarial pathogenesis.

GDF15 contributes to radioresistance and cancer stemness of head and neck cancer by regulating cellular reactive oxygen species via a SMAD-associated signaling pathway

“…For this, an antioxidant agent, N-acetylcysteine (NAC), was used to reduce cellular ROS levels [35, 36]. The effect of NAC on radiosensitivity was first examined.…”

Natural Phenolic Compounds and Derivatives as Potential Antimalarial Agents

“…In the symptomatic phase of malaria, which is understood as the erythrocytic stage of the parasiteʼs life cycle, the parasite has to maintain a relatively sensitive homeostasis. Particularly its redox homeostasis, since not only does its digestion of hemoglobin and the mitochondrial activity originate oxidative stress, but also the hostʼs immune system attacks with ROS [129,130]. The hostʼs erythrocyte is also receiving oxidative insults, which means the parasite must maintain both systemsʼ redox homeostasis if it wants to survive [43,129,130].…”

“…Particularly its redox homeostasis, since not only does its digestion of hemoglobin and the mitochondrial activity originate oxidative stress, but also the hostʼs immune system attacks with ROS [129,130]. The hostʼs erythrocyte is also receiving oxidative insults, which means the parasite must maintain both systemsʼ redox homeostasis if it wants to survive [43,129,130]. In the fight to prevent lipid peroxidation, inactivation of enzymes and ion channels, protein oxidation and inhibition of mitochondrial respiration, the parasite is equipped with an antioxidant system that includes glutathione proteins and superoxide dismutase [43].…”

“…In the fight to prevent lipid peroxidation, inactivation of enzymes and ion channels, protein oxidation and inhibition of mitochondrial respiration, the parasite is equipped with an antioxidant system that includes glutathione proteins and superoxide dismutase [43]. When antimalarials are able to saturate this system and disturb the already fragile redox balance, the cascade of oxidative damage ensures the parasiteʼs death [130]. Flavonoids are recognized powerful antioxidants that, in certain conditions of concentration and the presence of metal ions, as occurs within the erythrocytic stage of the parasite, act as pro-oxidants.…”

“…Studies have shown that the higher the oxidation potential of phenols, the higher the selectivity toward the parasite [106], which means phenolic compounds could be selected for their oxidation potential in order to improve their selectivity and, consequently, antiplasmodial activity. However, considering that this potential depends on certain conditions, if the antioxidant potential overthrows the oxidant, the antiplasmodial activity might become compromised, begging the question if this type of activity is reliable in the context of malaria [130]. ▶ Table 9 gives an overview on the antioxidant potential of some of the discussed antiplasmodial phenolic compounds.…”