Oxidative stress in malaria and artemisinin combination therapy: Pros and Cons

Kavishe, Reginald A.; Koenderink, Jan B.; Alifrangis, Michael

doi:10.1111/febs.14097

Cited by 95 publications

(82 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that prior treatment with mild ROS generatros may upregulate expression of hypoxia-inducible factor (HIF) and erythropoietin (Epo), and therefore protect neurons against subsequent ROS stress (Liu et al, 2005 ). Pretreatment with artemisinin may react with intracellular heme and elicit low levels production of ROS, which could protect cells from lethal ROS insult induced by glutamate damage (Schmuck et al, 2002 ; Kavishe et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Artemisinin Prevents Glutamate-Induced Neuronal Cell Death Via Akt Pathway Activation

Lin

Winters

et al. 2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Artemisinin is an anti-malarial drug that has been in use for almost half century. Recently, novel biological effects of artemisinin on cancer, inflammation-related disorders and cardiovascular disease were reported. However, neuroprotective actions of artemisinin against glutamate-induced oxidative stress have not been investigated. In the current study, we determined the effect of artemisinin against oxidative insult in HT-22 mouse hippocampal cell line. We found that pretreatment of artemisinin declined reactive oxygen species (ROS) production, attenuated the collapse of mitochondrial membrane potential induced by glutamate and rescued HT-22 cells from glutamate-induced cell death. Furthermore, our study demonstrated that artemisinin activated Akt/Bcl-2 signaling and that neuroprotective effect of artemisinin was blocked by Akt-specific inhibitor, MK2206. Taken together, our study indicated that artemisinin prevented neuronal HT-22 cell from glutamate-induced oxidative injury by activation of Akt signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Artemisinin Prevents Glutamate-Induced Neuronal Cell Death Via Akt Pathway Activation

Lin

Winters

et al. 2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The mechanisms of how artemisinin and its derivatives, such as artesunate and artemether, attain antimalarial activity are thought to reside in generating oxidative stress by liberating reactive oxygen species from an internal peroxo-moiety, and in affecting a calcium ATPase (SERCA or PfATP6) of the sarcoplasmic-endoplasmic reticulum (Moore et al, 2011 ). The half-life of the fast-acting artemisinins is very short, typically around 1 h. To maintain this highly efficient therapeutic option in view of an increasing number of mutant parasite strains with varying degrees of resistance to the artemisinins (Jambou et al, 2005 ), these compounds are combined with drugs that exhibit longer half-lives (WHO, 2001 ; Kavishe et al, 2017 ). Patients infected with P. vivax, Plasmodium ovale, Plasmodium malariae , or Plasmodium knowlesi are equally treated with an artemisinin combination therapy or with chloroquine depending on the sensitivity of the infecting strain.…”

Section: Human-pathogenic Protozoa Current Treatment Resistancementioning

confidence: 99%

Targeting Channels and Transporters in Protozoan Parasite Infections

2018

View full text Add to dashboard Cite

Infectious diseases caused by pathogenic protozoa are among the most significant causes of death in humans. Therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains. Many of the current anti-parasite drugs target soluble enzymes, generate unspecific oxidative stress, or act by an unresolved mechanism within the parasite. In recent years, collections of drug-like compounds derived from large-scale phenotypic screenings, such as the malaria or pathogen box, have been made available to researchers free of charge boosting the identification of novel promising targets. Remarkably, several of the compound hits have been found to inhibit membrane proteins at the periphery of the parasites, i.e., channels and transporters for ions and metabolites. In this review, we will focus on the progress made on targeting channels and transporters at different levels and the potential for use against infections with apicomplexan parasites mainly Plasmodium spp. (malaria) and Toxoplasma gondii (toxoplasmosis), with kinetoplastids Trypanosoma brucei (sleeping sickness), Trypanosoma cruzi (Chagas disease), and Leishmania ssp. (leishmaniasis), and the amoeba Entamoeba histolytica (amoebiasis).

show abstract

“…ART rely on their rapid conversion to reactive free radicals for potent antimalarial activity. However, their very short clearance half-life (~1h) combined with under dosage of infected patients and incomplete drug treatment may contribute to the occurrence and spread of ART resistance [ 17 , 18 , 19 ]. Exacerbating the situation, patients frequently undergo incomplete treatment [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Induction of high tolerance to artemisinin by sub-lethal administration: A new in vitro model of P. falciparum

et al. 2018

View full text Add to dashboard Cite

Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum parasite clearance half-life following treatment with artemisinin-based combination therapies (ACTs) and an increase in the percentage of surviving parasites. The remarkably short blood half-life of artemisinin derivatives may contribute to drug-resistance, possibly through factors including sub-lethal plasma concentrations and inadequate exposure. Here we selected for a new strain of artemisinin resistant parasites, termed the artemisinin resistant strain 1 (ARS1), by treating P. falciparum Palo Alto (PA) cultures with sub-lethal concentrations of dihydroartemisinin (DHA). The resistance phenotype was maintained for over 1 year through monthly maintenance treatments with low doses of 2.5 nM DHA. There was a moderate increase in the DHA IC50 in ARS1 when compared with parental strain PA after 72 h of drug exposure (from 0.68 nM to 2 nM DHA). In addition, ARS1 survived treatment physiologically relevant DHA concentrations (700 nM) observed in patients. Furthermore, we confirmed a lack of cross-resistance against a panel of antimalarials commonly used as partner drugs in ACTs. Finally, ARS1 did not contain Pfk13 propeller domain mutations associated with ART resistance in the Greater Mekong Region. With a stable growth rate, ARS1 represents a valuable tool for the development of new antimalarial compounds and studies to further elucidate the mechanisms of ART resistance.

show abstract

Oxidative stress in malaria and artemisinin combination therapy: Pros and Cons

Cited by 95 publications

References 102 publications

Artemisinin Prevents Glutamate-Induced Neuronal Cell Death Via Akt Pathway Activation

Artemisinin Prevents Glutamate-Induced Neuronal Cell Death Via Akt Pathway Activation

Targeting Channels and Transporters in Protozoan Parasite Infections

Induction of high tolerance to artemisinin by sub-lethal administration: A new in vitro model of P. falciparum

Contact Info

Product

Resources

About