Thorium decorporation efficacy of rationally-selected biocompatible compounds with relevance to human application

Ali, Manjoor; Sadhu, Biswajit; Boda, Anil; Tiwari, Nidhi; Das, Amit Kumar; Ali, Sardar; Bhattacharya, Dibyendu; Pandey, Badri N.; Kumar, Amit

doi:10.1016/j.jhazmat.2018.11.038

Cited by 17 publications

(9 citation statements)

References 39 publications

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“…We have reported synergic radioprotective effects of silibinin with pterostilbene, resulting in 100% of the mice surviving, 30 days after TBI g-irradiation of 7.6 Gy (LD50/30) [ 141 ]. Silibinin can chelate thorium radionuclides ( 232 Th) preventing hemolysis and enhancing liver cells decorporation, which is important because those cells are the major targets of internalized 232 Th [ 143 ].…”

Section: Medical Countermeasuresmentioning

confidence: 99%

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

et al. 2022

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Atomic and radiological crises can be caused by accidents, military activities, terrorist assaults involving atomic installations, the explosion of nuclear devices, or the utilization of concealed radiation exposure devices. Direct damage is caused when radiation interacts directly with cellular components. Indirect effects are mainly caused by the generation of reactive oxygen species due to radiolysis of water molecules. Acute and persistent oxidative stress associates to radiation-induced biological damages. Biological impacts of atomic radiation exposure can be deterministic (in a period range a posteriori of the event and because of destructive tissue/organ harm) or stochastic (irregular, for example cell mutation related pathologies and heritable infections). Potential countermeasures according to a specific scenario require considering basic issues, e.g., the type of radiation, people directly affected and first responders, range of doses received and whether the exposure or contamination has affected the total body or is partial. This review focuses on available medical countermeasures (radioprotectors, radiomitigators, radionuclide scavengers), biodosimetry (biological and biophysical techniques that can be quantitatively correlated with the magnitude of the radiation dose received), and strategies to implement the response to an accidental radiation exposure. In the case of large-scale atomic or radiological events, the most ideal choice for triage, dose assessment and victim classification, is the utilization of global biodosimetry networks, in combination with the automation of strategies based on modular platforms.

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Section: Medical Countermeasuresmentioning

confidence: 99%

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

et al. 2022

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“…These drugs act as chelating agents to trap internalized radionuclides and expedite their excretion via urine and feces. However, there remains a scarcity of decorporation agents, particularly for actinides . For instance, diethylenetriamine pentaacetic acid (DTPA) is the only Food and Drug Administration (FDA) approved drug for decorporation of plutonium (Pu).…”

Section: Introductionmentioning

confidence: 99%

Periodic trends and complexation chemistry of tetravalent actinide ions with a potential actinide decorporation agent 5‐LIO(Me‐3,2‐HOPO): A relativistic density functional theory exploration

2020

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A relativistic density functional theory (DFT) study is reported which aims to understand the complexation chemistry of An 4+ ions (An = Th, U, Np, and Pu) with a potential decorporation agent, 5-LIO(Me-3,2-HOPO). The calculations show that the periodic change of the metal binding free energy has an excellent correlation with the ionic radii and such change of ionic radii also leads to the structural modulation of actinide-ligand complexes. The calculated structural and binding parameters agree well with the available experimental data. Atomic charges derived from quantum theory of atoms in molecules (QTAIM) and natural bond order (NBO) analysis shows the major role of ligand-to-metal charge transfer in the stability of the complexes. Energy decomposition analysis, QTAIM, and electron localization function (ELF) predict that the actinide-ligand bond is dominantly ionic, but the contribution of orbital interaction is considerable and increases from Th 4+ to Pu 4+ . A decomposition of orbital contributions applying the extended transition state-natural orbital chemical valence method points out the significant π-donation from the oxygen donor centers to the electron-poor actinide ion. Molecular orbital analysis suggests an increasing trend of orbital mixing in the context of 5f orbital participation across the tetravalent An series (Th-Pu). However, the corresponding overlap integral is found to be smaller than in the case of 6d orbital participation. An analysis of the results from the aforementioned electronic structure methods indicates that such orbital participation possibly arises due to the energy matching of ligand and metal orbitals and carries the signature of near-degeneracy driven covalency. K E Y W O R D S actinide, covalency, decorporation agent, density functional theory, ETS-NOCV, QTAIM

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“…The main classes of these agents are (1) polyaminopolycarboxylics [diethylenetriaminepentaacetic acid (DTPA)], (2) siderophores (catechol and pyridinone), and (3) macrocycles (calixarenes and crown ethers). Calixarene and crown ether families are potential ligands for actinides; however, these ligands were found to be significantly toxic. , Among all of these decorporating agents, DTPA has been shown to be most effective for actinide decorporation and is the only approved antidote by U.S. Food and Drug administration (FDA) for Pu, curium, and americium decorporation. ,− Although it forms stable complexes with actinides, DTPA has several limitations such as poor oral bioavailability (∼3%), the requirement of intravenous administration, less retention time in blood plasma, and an inability to reach to actinide-depository organs, etc. ,− Moreover, the long-term uses of DTPA antidote causes calcium (Ca) and magnesium deficiency, which leads to neurotoxicity, nephrotoxicity, hematopoiesis suppression, etc . Recently, there has been an attempt to explore derivatives of DTPA such as polyethylenimine for Th decorporation; however, the studies are limited to Th complexation without any in vitro/in vivo biological studies .…”

Section: Introductionmentioning

confidence: 99%

Combined Thermodynamic, Theoretical, and Biological Study for Investigating N-(2-Acetamido)iminodiacetic Acid as a Potential Thorium Decorporation Agent

Sharma,

Ali,

Kumar

et al. 2023

Inorg. Chem.

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The most effective approach to mitigate the toxic effects of internal exposure of radiometals to humans is metal–ligand (ML) chelation therapy. Thorium (Th)-induced carcinogenesis as well as other health hazards to humans as a result of chronic internal exposure necessitates the development of efficient Th-decorporating agents. In this regard, chemical and biological studies were carried out to evaluate N-(2-Acetamido)iminodiacetic acid (ADA), a comparatively cost-effective, readily available, and biologically safe complexing agent for Th decorporation. In the present work, detailed thermodynamic studies for complexation of ADA with Th(IV) have been carried out to understand Th-ADA interaction, using potentiometry, calorimetry, electrospray ionization mass spectrometry, and theoretical studies, followed by its biological assessment for Th decorporation. Thermodynamic studies revealed the formation of strong Th-ADA complexes, which are enthalpically as well as entropically favored. Interestingly, density functional theory calculations, to obtain a thermodynamically favored mode of coordination, showed the uncommon trend of lower denticity of ADA in ML than in ML2, which has been explained on the basis of stabilization of ML by hydrogen bonding. The same was also reflected in the unusual trend of enthalpy for Th-ADA complexes. Biological experiments using human erythrocytes, whole human blood, and lung cells showed good cytocompatibility and ability of ADA to significantly prevent Th-induced hemolysis. Th removal of ADA from erythrocytes, human blood, and normal lung cells was found to be comparable with that of diethylenetriamine pentaacetate (DTPA), an FDA approved decorporating agent. The present study contributed significant data about Th complexation chemistry of ADA and its Th decorporation efficacy from human erythrocytes, blood, and lung cells.

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Thorium decorporation efficacy of rationally-selected biocompatible compounds with relevance to human application

Cited by 17 publications

References 39 publications

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

Periodic trends and complexation chemistry of tetravalent actinide ions with a potential actinide decorporation agent 5‐LIO(Me‐3,2‐HOPO): A relativistic density functional theory exploration

Combined Thermodynamic, Theoretical, and Biological Study for Investigating N-(2-Acetamido)iminodiacetic Acid as a Potential Thorium Decorporation Agent

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