When radionuclides are accidentally ingested or inhaled, blood circulation or tissue/organ deposition of the radionuclides causes systemic or local radiation effects. In such cases, decorporation therapy is used to reduce the health risks due to their intake. Decorporation therapy includes reduction and/or inhibition of absorption from the gastrointestinal tract, isotopic dilution, and the use of diuretics, adsorbents, and chelating agents. For example, penicillamine is recommended as a chelating agent for copper contamination, and diethylene triamine pentaacetic acid is approved for the treatment of internal contamination with plutonium. During chelation therapy, the removal effect of the drugs should be monitored using a whole-body counter and/or bioassay. Some authorities, such as the National Council on Radiation Protection and Measurements and International Atomic Energy Agency, have reported recommended decorporation agents for each radionuclide. However, few drugs are approved by the US Food and Drug Administration, and many are off-label-use agents. Because many decontamination agents are drugs that have been available for a long time and have limited efficacy, the development of new, higher-efficacy drugs has been carried out mainly in the USA and France. In this article, in addition to an outline of decorporation agents for internal radioactive contamination, an outline of our research on decorporation agents for actinide (uranium and plutonium) contamination and for radio-cesium contamination is also presented.
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http://dx.doi.org/10.1248/yakushi.14-00227-3 | DOI Listing |
Molecules
December 2024
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Inhalation of aerosolized uranium is recognized as a principal mode of exposure, posing significant risks of damage to the lungs, kidneys, and other vital organs. To enhance nuclide elimination from the body, chelating agents are employed; however, single-component chelators often exhibit limited spectral activity and low effectiveness, resulting in toxicologically relevant concentrations. We have developed a composite chelating agent composed of 3,4,3-Li(1,2-HOPO), DFP, and HEDP in optimized ratios, demonstrating marked improvements in eliminating inhaled uranium.
View Article and Find Full Text PDFRSC Adv
December 2024
School of Safety Science and Emergency Management, Wuhan University of Technology Wuhan 430070 China.
Searching for highly selective, efficient, and low-toxicity chelating agents is central to resolving uranium contamination . Peptides composed of amino acids exhibit very low toxicity for accumulation in the human body and have been proven effective in chelating actinides within the human body. Herein, we report a rationally designed short phosphorylated peptide sequence PP-B, which exhibits high affinity and selectivity for uranyl compared to other trace elements present in the body (such as Na, K, Ca, Co, Fe, Fe, Mg, Mn, Zn).
View Article and Find Full Text PDFAdv Healthc Mater
January 2025
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University, Chongqing, 400038, China.
J Chromatogr A
October 2024
Université Paris-Saclay, CEA, Service de Physico Chimie, Gif-sur-Yvette F-91191, France. Electronic address:
In the field of nuclear toxicology, the knowledge of the interaction of actinides (An) with biomolecules is of prime concern in order to elucidate their toxicity mechanism and to further develop selective decorporating agents. In this work, we demonstrated the great potential of hydrophilic interaction liquid chromatography (HILIC) to separate polar thorium (Th) biomimetic peptide complexes, as a key starting point to tackle these challenges. Th was used as plutonium (Pu) analogue and pS16 and pS1368 as synthetic di- and tetra-phosphorylated peptides capable of mimicking the interaction sites of these An in osteopontin (OPN), a hyperphosphorylated protein.
View Article and Find Full Text PDFPharmaceuticals (Basel)
July 2024
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Radionuclide uranium has both a chemical and radioactive toxicity, leading to severe nephrotoxicity as it predominantly deposits itself in the kidneys after entering into human bodies. It crosses renal cell membranes, accumulates in mitochondria and causes mitochondrial oxidative damage and dysfunction. In this study, a mitochondria-targeted heptamethine indocyanine small molecule chelator modified with gallic acid (IR-82) is synthesized for uranium detoxication.
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