Lacunary Selenotungstate Serves as a Therapeutic Agent for Uranium Intake

IF 4.3 2区 化学 Q1 CHEMISTRY, INORGANIC & NUCLEAR
Jingwen Guan, Xiaomei Wang, Yemeng Chen, Hailong Zhang, Zongyi Li, Ao Li, Fuwan Zhai, Lanhua Chen, Lei Chen, Ximeng Li, Bin Chen, Yigong Xu, Xiao Dong, Wei Liu, Xing Dai, Shuao Wang, Juan Diwu
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引用次数: 0

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.

Abstract Image

硒钨酸盐作为一种治疗铀摄入的药物
铀的内部污染由于其化学和放射性毒性,在发生核事故时对专业人员和公众构成严重的健康风险。虽然螯合疗法被认为是紧急情况下唯一可行的治疗方法,但目前的临床螯合剂对铀的疗效有限。在此,最近设计的一种间隙硒钨酸盐多金属氧酸盐(Se6W45)被证明是一种有效的治疗剂。在这个结构中,Se6W45的开放位点提供了一个合适的铀结合环境,导致肾(85.87%)和股骨(39.81%)的铀选择性去除,配体/金属比极低,仅为4:1。Se6W45中的氧化还原活性位点,主要是掺入的硒,能够将暴露于铀的NRK-52E细胞内的细胞内活性氧(ROS)降低到正常水平。这种方法克服了目前螯合配体在100- 1000倍范围内过度使用的缺点,避免了相应的异相阳离子消耗,蛋白质功能障碍和/或酸碱失衡。更重要的是,它在减少辐射损伤和化学毒性方面为铀提供了一种协同解毒疗法。
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来源期刊
Inorganic Chemistry
Inorganic Chemistry 化学-无机化学与核化学
CiteScore
7.60
自引率
13.00%
发文量
1960
审稿时长
1.9 months
期刊介绍: Inorganic Chemistry publishes fundamental studies in all phases of inorganic chemistry. Coverage includes experimental and theoretical reports on quantitative studies of structure and thermodynamics, kinetics, mechanisms of inorganic reactions, bioinorganic chemistry, and relevant aspects of organometallic chemistry, solid-state phenomena, and chemical bonding theory. Emphasis is placed on the synthesis, structure, thermodynamics, reactivity, spectroscopy, and bonding properties of significant new and known compounds.
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