Resistance to artemisinin in falciparum malaria parasites: A redox-mediated phenomenon

Egwu, Chinedu Ogbonnia; Pério, Pierre; Augereau, Jean‐Michel; Tsamesidis, Ioannis; Benoit‐Vical, Françoise; Reybier, Karine

doi:10.1016/j.freeradbiomed.2021.08.016

Cited by 30 publications

(34 citation statements)

References 58 publications

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“…ACTs with newer molecules that disrupt the resistance mechanism of the parasite should be sought. Such molecules, companion drugs of artemisinin, could target key antioxidant enzymes linked to glutathione-dependent and thioredoxin-dependent systems, phosphatidyl inositol 4-kinase enzyme (PI4K), and mRNA translation pathways in Plasmodium [ 69 , 144 , 145 , 146 , 147 ]. ROS generation thus remains a key element in the strategy in the fight against Plasmodium and sustainable malaria control.…”

Section: Discussionmentioning

confidence: 99%

“…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 , 70 , 71 ].…”

Section: Sources and Management Of Ros In Plasmodium -Infected Erythrocytes Under Steady Statementioning

confidence: 99%

“…This depolarization can be caused by the direct inhibition of PfATPase6 by artemisinins and other endoperoxides [ 119 ]. Artemisinins can also generate ROS at the mitochondrial level by altering the transfer of electrons from complex III to molecular oxygen, forming superoxide radicals [ 16 , 38 , 69 , 112 ].…”

Section: Ros Production In Plasmodium -Infected Erythrocytes Under Antimalarial Treatmentmentioning

confidence: 99%

“…Increased expression of antioxidants: Because of the elevated ROS generation due to antimalarial treatment, parasites increase their expression of vital antioxidant enzymes. Such enzymes include iron-superoxide synthetase (Fe-SOD), glutathione-S-transferase (GST), glutathione synthetase (GS), γ-glutamylcysteine synthetase (γ-GCS), thioredoxin reductase (TrxR), and peroxiredoxins (nPrx) [ 69 , 70 , 136 ]. This overexpression, which is higher in the artemisinins-resistant strains, especially SOD and GST, is associated with parasite resistance characterized by a lower level of ROS and less oxidized proteins [ 69 ].…”

Section: Ros Production In Plasmodium -Infected Erythrocytes Under Antimalarial Treatmentmentioning

confidence: 99%

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Reactive Oxygen Species as the Brainbox in Malaria Treatment

et al. 2021

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Several measures are in place to combat the worldwide spread of malaria, especially in regions of high endemicity. In part, most common antimalarials, such as quinolines and artemisinin and its derivatives, deploy an ROS-mediated approach to kill malaria parasites. Although some antimalarials may share similar targets and mechanisms of action, varying levels of reactive oxygen species (ROS) generation may account for their varying pharmacological activities. Regardless of the numerous approaches employed currently and in development to treat malaria, concerningly, there has been increasing development of resistance by Plasmodium falciparum, which can be connected to the ability of the parasites to manage the oxidative stress from ROS produced under steady or treatment states. ROS generation has remained the mainstay in enforcing the antiparasitic activity of most conventional antimalarials. However, a combination of conventional drugs with ROS-generating ability and newer drugs that exploit vital metabolic pathways, such antioxidant machinery, could be the way forward in effective malaria control.

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Section: Discussionmentioning

confidence: 99%

Section: Sources and Management Of Ros In Plasmodium -Infected Erythrocytes Under Steady Statementioning

confidence: 99%

Section: Ros Production In Plasmodium -Infected Erythrocytes Under Antimalarial Treatmentmentioning

confidence: 99%

Section: Ros Production In Plasmodium -Infected Erythrocytes Under Antimalarial Treatmentmentioning

confidence: 99%

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Reactive Oxygen Species as the Brainbox in Malaria Treatment

et al. 2021

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“…Plasmodium is the causative pathogen of malaria and are harmful to human health ( 62 ). Approximately 50% of the global population is at risk of Plasmodium infection.…”

Section: Phylum Apicomplexa Class Sporozoasidamentioning

confidence: 99%

The State of Art of Extracellular Traps in Protozoan Infections (Review)

2021

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Protozoan parasite infection causes severe diseases in humans and animals, leading to tremendous economic and medical pressure. Natural immunity is the first line of defence against parasitic infection. Currently, the role of natural host immunity in combatting parasitic infection is unclear, so further research on natural host immunity against parasites will provide a theoretical basis for the prevention and treatment of related parasitic diseases. Extracellular traps (ETs) are an important natural mechanism of immunity involving resistance to pathogens. When immune cells such as neutrophils and macrophages are stimulated by external pathogens, they release a fibrous network structure, consisting mainly of DNA and protein, that can capture and kill a variety of extracellular pathogenic microorganisms. In this review, we discuss the relevant recently reported data on ET formation induced by protozoan parasite infection, including the molecular mechanisms involved, and discuss the role of ETs in the occurrence and development of parasitic diseases.

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Malaria

Tripathi,

Bhatt

2024

The Diagnosis and Treatment of Protozoan Diseases

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Resistance to artemisinin in falciparum malaria parasites: A redox-mediated phenomenon

Cited by 30 publications

References 58 publications

Reactive Oxygen Species as the Brainbox in Malaria Treatment

Reactive Oxygen Species as the Brainbox in Malaria Treatment

The State of Art of Extracellular Traps in Protozoan Infections (Review)

Malaria

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