A quick and simple in vitro assay to predict bioavailability of actinides following accidental exposure

Meeren, Anne Van der; Angulo, Jaime F.; Bohand, Sandra; Griffiths, N. M.

doi:10.1016/j.tiv.2019.03.027

Cited by 10 publications

(13 citation statements)

References 18 publications

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“…The presence of phosphate in the static phase markedly limits the transferability of both Pu(IV) and Am(III) but to a higher extent for Am. This is in line with previous data showing the higher retention of Am by the calcium phosphate mineral, hydroxyapatite compartment of bone, as compared to Pu [ 35 , 48 ]. Secondly, we showed that the presence of phosphate in the static phase limits the efficacy of DTPA on Pu transfer whereas an opposite situation is observed for Am.…”

Section: Discussionsupporting

confidence: 93%

“…Our previous work suggested that this assay could reflect interactions occurring in biological surroundings when the static phases are made or incubated in the presence of potential ligands, either endogenous or exogenous. Thus, we were able to demonstrate, in accordance with in vivo data, that bioavailability depends on (i) the nature and the physicochemical form of the actinide and (ii) the nature of the ligands in the static or dynamic phases [34,35]. In addition, the data obtained from this assay with An was found to show good correlation between dissolution data and urinary excretion following contamination in rat [34,36].…”

Section: Introductionsupporting

confidence: 78%

“…Thus, we compared the transfer of Pu and Am from a static phase made with NaCl/KCl or DPBS to the dynamic phase where DTPA is added at various concentrations (5-500 µM). A time-related dose-response In our previous work, we demonstrated that transfer of Pu and Am from the static phase prepared in saline solution is increased in the presence of exogenous ligands, such as DTPA added in the dynamic phase [34,35]. This suggested that a diffusion of DTPA from the dynamic to the static phase occurred, allowing the formation of actinide-DTPA complexes within the gels, followed by a rapid transfer to the dynamic phase and elimination during the replacement of the dynamic phase at each collection time.…”

Section: Transfer Of Pu/am In the Presence Of A Synthetic Ligand (Dtp...mentioning

confidence: 99%

“…This is illustrated by the differential efficacy of the currently approved chelating drug for actinide decorporation, i.e., diethylenetriaminpentaacetic acid (DTPA) according to the route of An Intake and its physicochemical form [4]. Despite the higher affinity of DTPA towards Pu (logK [29][30][31][32][33][34][35][36] as compared to Am (logK 23-26) (for reviews, see [1,5]), the higher efficacy of DTPA for the decorporation of Am as compared to Pu is generally attributed to the higher in vivo bioavailability of Am [6,7]. In line with this hypothesis, Paquet and colleagues demonstrated a better decorporation of Am as compared to Pu using the octadentate ligand 3,4,3-LI(1,2-HOPO) following wound contamination with MOX nuclear fuel [8].…”

Section: Introductionmentioning

confidence: 99%

“…To improve the characterization of An-bioligand interactions in more physiologically relevant environments, we recently developed a biphasic and dynamic in vitro acellular assay [ 34 , 35 ]. This assay mimics the transfer of bioavailable An species from a retention compartment (agarose gel) to a dynamic fluid phase (transfer compartment) under stirring at 37 °C and in a 5% CO 2 atmosphere.…”

Section: Introductionmentioning

confidence: 99%

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Use of an Acellular Assay to Study Interactions between Actinides and Biological or Synthetic Ligands

et al. 2022

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Speciation of actinides, and more particularly bioligand-binding ability, influences in vivo behavior. Understanding these interactions is essential for estimation of radiological dose and improvement of decorporation strategies for accidentally contaminated victims. Because the handling of actinides imposes overwhelming difficulties, in vitro assays carried out in physiological conditions are lacking and data regarding such interactions are scarce. In this study, we used a bi-compartmental and dynamic assay, providing physiological conditions (presence of inorganic ions, pH, temperature) to explore interactions between the actinides plutonium (Pu) and americium (Am) and endogenous (proteins transferrin and ferritin) or exogenous ligands (the chelating agent diethylenetriaminpentaacetic acid, DTPA). In this assay, an agarose gel represents the retention compartment of actinides and a dynamic fluid phase, the transfer compartment. The proportion of actinides transferred from static to dynamic phase reflects interactions between Pu/Am and various ligands. The results show differences in the formation of actinide-protein or actinide-DTPA complexes in physiologically relevant media depending on which ligand is present and where. We observed differential behavior for Pu and Am similar to in vivo studies. Thus, our assay may be used to determine the ability of various actinides to interact with specific proteins or with drug candidates for decorporation in complex physiologically relevant environments.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionsupporting

confidence: 78%

Section: Transfer Of Pu/am In the Presence Of A Synthetic Ligand (Dtp...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Use of an Acellular Assay to Study Interactions between Actinides and Biological or Synthetic Ligands

et al. 2022

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Immobilization of controlled Pu:Am ratio on actinide-specific affinity monolith support developed in capillary and coupled to inductively coupled plasma mass spectrometry

Barhoum,

Garcia-Cortes,

Boudias

et al. 2024

Microchim Acta

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In vitro assessment of cobalt oxide particle dissolution in simulated lung fluids for identification of new decorporating agents

Meeren

Lemaire

Coudert

et al. 2020

Toxicology in Vitro

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Inhalation of 60 Co3O4 particles may occur at the work place in nuclear industry. Their low solubility may result in chronic lung exposure to γ rays. Our strategy for an improved therapeutic approach is to enhance particle dissolution to facilitate cobalt excretion, as the dissolved fraction is rapidly eliminated, mainly in urine. In vitro dissolution of Co3O4 particles was assessed with two complementary assays in lung fluid surrogates to mimic a pulmonary contamination scenario. Twenty-one molecules and eleven combinations were selected through an extensive search in the literature, based on dissolution studies of other metal oxides (Fe, Mn, Cu) and tested for dissolution enhancement of cobalt particles after 1 to 28 days of incubation. DTPA, the recommended treatment following cobalt contamination did not enhance 60 Co3O4 particles dissolution when used alone. However, by combining molecules with different properties, such as redox potential and chelating ability, we greatly improved the efficacy of each drug used alone, leading for the highest efficacy, to a 2.7 fold increased dissolution as compared to controls. These results suggest that destabilization of the particle surface is an important initiating event for a good efficacy of chelating drugs, and open new perspectives for the identification of new therapeutic strategies.

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A quick and simple in vitro assay to predict bioavailability of actinides following accidental exposure

Cited by 10 publications

References 18 publications

Use of an Acellular Assay to Study Interactions between Actinides and Biological or Synthetic Ligands

Use of an Acellular Assay to Study Interactions between Actinides and Biological or Synthetic Ligands

Immobilization of controlled Pu:Am ratio on actinide-specific affinity monolith support developed in capillary and coupled to inductively coupled plasma mass spectrometry

In vitro assessment of cobalt oxide particle dissolution in simulated lung fluids for identification of new decorporating agents

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