Iron chelators: correlation between effects on Plasmodium spp. and immune functions

The Journal of Parasitology
Jacob GolenserPeter Kremsner

Abstract

Iron chelating agents, which permeate through erythrocytic and parasite membranes, are effective against Plasmodium falciparum in vitro. However, the protective effect in humans is transient. We examined the antiplasmodial capacity of several iron chelators in vitro and in vivo. The chelators 3/3hb/2m and 3/2hb/b (together, MoB) were more effective against P. falciparum in vitro than desferrioxamine (DFO) and Salicylaldehyde isonicotinoyl hydrazone (SIH) (together, DoS). Despite similar pharmacokinetics of all iron chelators, mice infected with Plasmodium vinckei and treated with MoB succumbed to malaria, whereas DoS-treated mice survived. However, even in the surviving mice, peak parasitemias were above 30%. These results indicate that the direct effects of the drugs on the parasites were not responsible alone for the complete recovery of the mice. We suggest that the recovery is related to differential effects of the drugs on various immune functions. We concentrated on the effect of the iron chelators on B cell and T cell proliferation and on allogeneic stimulation (MLR), interleukin-10 (IL-10), gamma-interferon (gamma-IFN), tumor necrosis factor-alpha (TNF-alpha), and radical production. All the iron chelators examined inhi...Continue Reading

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Citations

Apr 11, 2007·Infection and Immunity·Aaron L NelsonJeffrey N Weiser
Sep 7, 2007·Microbiology and Molecular Biology Reviews : MMBR·Marcus Miethke, Mohamed A Marahiel
Nov 28, 2012·Autoimmunity·Hong Zan, Paolo Casali
May 17, 2014·Frontiers in Pharmacology·Martha A ClarkCarla Cerami
Jul 7, 2020·Metallomics : Integrated Biometal Science·Jan Mach, Robert Sutak
Feb 27, 2008·Food and Nutrition Bulletin·Andrew M PrenticeSharon E Cox
Feb 5, 2021·International Journal of Pharmaceutics·Di Fan, Qiaojun Fang

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay

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