Iron Chelation Therapy for Malaria

Mabeza, George; Loyevsky, Mark; Gordeuk, Victor R.; Weiss, Günter

doi:10.1016/s0163-7258(98)00037-0

Cited by 106 publications

(87 citation statements)

References 160 publications

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“…Numerous in vitro and in vivo studies confirm that reducing iron availability through application of iron-chelating agents is an effective method to stunt the proliferation of parasites. 11 During the blood stage, iron deficiency may confer a protective effect by impairing the ability of Plasmodium falciparum to invade and propagate between erythrocytes. 12 In addition, recent experiments have also found that hepcidin-induced iron redistribution away from hepatocytes arrests the growth of intrahepatocytic parasites and thereby prevents the occurrence of malaria superinfections.…”

Section: Introductionmentioning

confidence: 99%

Cord Blood Hepcidin: Cross-Sectional Correlates and Associations with Anemia, Malaria, and Mortality in a Tanzanian Birth Cohort Study

Brickley

Spottiswoode

Kabyemela

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Hepcidin, the master regulator of bioavailable iron, is a key mediator of anemia and also plays a central role in host defense against infection. We hypothesized that measuring hepcidin levels in cord blood could provide an early indication of interindividual differences in iron regulation with quantifiable implications for anemia, malaria, and mortality-related risk. Hepcidin concentrations were measured in cord plasma from a birth cohort (N = 710), which was followed for up to 4 years in a region of perennial malaria transmission in Muheza, Tanzania (2002Tanzania ( -2006. At the time of delivery, cord hepcidin levels were correlated with inflammatory mediators, iron markers, and maternal health conditions. Hepcidin levels were 30% (95% confidence interval [CI]: 12%, 44%) lower in children born to anemic mothers and 48% (95% CI: 11%, 97%) higher in placental malaria-exposed children. Relative to children in the lowest third, children in the highest third of cord hepcidin had on average 2.5 g/L (95% CI: 0.1, 4.8) lower hemoglobin levels over the duration of follow-up, increased risk of anemia and severe anemia (adjusted hazard ratio [HR]

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Section: Introductionmentioning

confidence: 99%

Cord Blood Hepcidin: Cross-Sectional Correlates and Associations with Anemia, Malaria, and Mortality in a Tanzanian Birth Cohort Study

Brickley

Spottiswoode

Kabyemela

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…A large body of evidence links the severity and/or progression of cellular pathogenesis to cellular iron status (2,8,10,13,15,16,48). However, little is known about possible underlying mechanisms of this linkage.…”

Section: Fig 9 Bypyridyl Inhibits Hsv-1 Infection As Effectively Asmentioning

confidence: 99%

“…Pathogens and their hosts share this ambiguous relationship with iron (7)(8)(9)(10)(11)(12)(13). However, pathogens live within the context of the iron-restricted milieu that the host maintains as a key to the suppression of the cytotoxic potential of iron.…”

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confidence: 99%

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Intracellular Chelation of Iron by Bipyridyl Inhibits DNA Virus Replication

Romeo

Christen

Niles

et al. 2001

Journal of Biological Chemistry

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The efficient replication of large DNA viruses requires dNTPs supplied by a viral ribonucleotide reductase. Viral ribonucleotide reductase is an early gene product of both vaccinia and herpes simplex virus. For productive infection, the apoprotein must scavenge iron from the endogenous, labile iron pool(s). The membrane-permeant, intracellular Fe 2؉ chelator, 2,2-bipyridine (bipyridyl, BIP), is known to sequester iron from this pool. We show here that BIP strongly inhibits the replication of both vaccinia and herpes simplex virus, type 1. In a standard plaque assay, 50 M BIP caused a 50% reduction in plaque-forming units with either virus. Strong inhibition was observed only when BIP was added within 3 h post-infection. This time dependence was observed also in regards to inhibition of viral late protein and DNA synthesis by BIP. BIP did not inhibit the activity of vaccinia ribonucleotide reductase (RR), its synthesis, nor its stability indicating that BIP blocked the activation of the apoprotein. In parallel with its inhibition of vaccinia RR activation, BIP treatment increased the RNA binding activity of the endogenous iron-response protein, IRP1, by 1.9-fold. The data indicate that the diiron prosthetic group in vaccinia RR is assembled from iron taken from the BIP-accessible, labile iron pool that is sampled also by ferritin and the iron-regulated protein found in the cytosol of mammalian cells.

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“…A considerable number of iron(III) chelators, as well as certain iron(II) chelators, designed for purposes other than treating malaria have antimalarial activity in vitro (9). These facts directed us to check a potential of PQ-NSAIDs conjugates as iron chelators.…”

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confidence: 99%