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Lacunary Selenotungstate Serves as a Therapeutic Agent for Uranium Intake
Jingwen Guan1, Xiaomei Wang1, Yemeng Chen1
1State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection (SRMP), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
Abstract:
The internal contamination of uranium poses severe health risks to both professionals and the public in case of nuclear accidents due to its chemo- and radiotoxicity. Although chelation therapy has been considered the only practical treatment in emergencies, current clinical chelators show only limited efficacy for uranium. Herein, a recently designed lacunary selenotungstate polyoxometalate (Se6W45) was demonstrated as an effective therapeutic agent. In this construct, the open site in Se6W45 provides a suitable uranium binding environment, resulting in the selective removal of uranium from kidneys (85.87%) and femurs (39.81%) with an extremely low ligand/metal ratio of only 4:1. The redox active sites in Se6W45, primarily the incorporated selenium, were able to reduce the intracellular reactive oxygen species (ROS) to normal levels in NRK-52E cells exposed to uranium. This approach overcomes the disadvantages of the excessive use of current chelating ligands in the range from 100- to 1000-folds, avoiding the consequential depletion of heterogeneous cations, dysfunction of proteins, and/or acid-base imbalance. More importantly, it provides a synergistic antidotal therapy for uranium in reducing radiation damage and chemical toxicity.
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