Synergie potentielle entre deux toxiques rénaux : le DTPA et l’uranium

Müller, D.; Houpert, P.; Napoli, M. H. Henge; Métivier, Henri; Paquet, F.

doi:10.1051/radiopro:2006012

Cited by 6 publications

(1 citation statement)

References 9 publications

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“…However, DTPA was shown to be quite ineffective toward U(VI). Even worse, the use of DTPA in case of U(VI) contamination was proved to increase its nephrotoxicity . Ligands based on sulfocatecholate (TIRON) were the first chelating agents showing a modest reduction of acute U(VI) toxicity. − More recently promising ligands for actinide(IV) and (III) decorporation have been developed based on catecholate (CAM) and hydroxypyridonate (HOPO) attached to spatially suitable molecular backbones .…”

Section: Introductionmentioning

confidence: 99%

A Combined Spectroscopic/Molecular Dynamic Study for Investigating a Methyl-Carboxylated PEI as a Potential Uranium Decorporation Agent

et al. 2017

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Natural uranium has a very limited radioactive dose impact, but its chemical toxicity due to chronic exposure is still a matter of debate. Once inside the human body, the soluble uranium, under its uranyl form (U(VI)), is quickly removed from the blood system, partially excreted from the body, and partially retained in targeted organs, that is, the kidneys and bone matrix essentially. It is then crucial to remove or prevent the incorporation of uranium in these organs to limit the long-term chronic exposure. A lot of small chelating agents such as aminocarboxylates, catecholamides, and hydroxypyridonates have been developed so far. However, they suffer from poor selectivity and targeting abilities. Macromolecules and polymers are known to present a passive accumulation (size related), that is, the so-called enhanced permeability and retention effect, toward the main organs, which can be used as indirect targeting. Very interestingly, the methyl carboxylated polyethylenimine (PEI-MC) derivative has been described as a potent sequestering agent for heavy metals. It would be therefore an interesting candidate to evaluate as a new class of decorporation agents with passive targeting capabilities matching uranium preferential sequestering sites. In the present work, we explored the ability of a highly functionalized (89% rate) PEI-MC to uptake U(VI) close to physiological pH using a combination of analytical and spectroscopic techniques (inductively coupled plasma optical emission spectrometry (ICP-OES); extended X-ray absorption fine structure (EXAFS); and Fourier transformed infrared (FT-IR)) together with molecular dynamics (MD) simulation. A maximum loading of 0.47 mg U(VI) per milligram of PEI-MC was determined by ICP-OES measurements. From FT-IR data, a majority of monodentate coordination of the carboxylate functions of the PEI-MC seems to occur. From EXAFS and MD, a mix of mono and bidentate coordination mode was observed. Note that agreement between the EXAFS metrical parameters and MD radial distribution functions is remarkable. To the best of our knowledge, this is the first comprehensive structural study of a macromolecular PEI-based agent considered for uranium decorporation purposes.

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Section: Introductionmentioning

confidence: 99%