Feng Yiping, Wu Jingyi, Lu Haijian, Lao Wenhao, Zhan Hongda, Lin Longyong, Liu Guoguang, Deng Yirong
Guangzhou Key Laboratory Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, China.
Guangdong Key Laboratory of Contaminated Sites Environmental Management and Remediation, Guangdong Provincial Academy of Environmental Science, Guangzhou 510045, China.
Sci Total Environ. 2023 Jun 25;879:163259. doi: 10.1016/j.scitotenv.2023.163259. Epub 2023 Apr 1.
The widespread application of rare earth elements (REEs) has raised concerns about their potential release into the environment and subsequent ingestion by humans. Therefore, it is essential to evaluate the cytotoxicity of REEs. Here, we investigated the interactions between three typical REEs (La, Gd, and Yb) ions as well as their nanometer/μm-sized oxides and red blood cells (RBCs), a plausible contact target for nanoparticles when they enter the bloodstream. Hemolysis of REEs at 50-2000 μmol L was examined to simulate their cytotoxicity under medical or occupational exposure. We found that the hemolysis due to the exposure of REEs was highly dependent on their concentration, and the cytotoxicity followed the order of La > Gd > Yb. The cytotoxicity of REE ions (REIs) is higher than REE oxides (REOs), while nanometer-sized REO caused more hemolysis than that μm-sized REO. The production of reactive oxygen species (ROS), ROS quenching experiment, as well as the detection of lipid peroxidation, confirmed that REEs causes cell membrane rupture by ROS-related chemical oxidation. In addition, we found that the formation of a protein corona on REEs increased the steric repulsion between REEs and cell membranes, hence mitigating the cytotoxicity of REEs. The theoretical simulation indicated the favorable interaction of REEs with phospholipids and proteins. Therefore, our findings provide a mechanistic explanation for the cytotoxicity of REEs to RBCs once they have entered the blood circulation system of organisms.
稀土元素（REEs）的广泛应用引发了人们对其可能释放到环境中并随后被人类摄入的担忧。因此，评估稀土元素的细胞毒性至关重要。在此，我们研究了三种典型稀土元素（镧、钆和镱）离子及其纳米/微米级氧化物与红细胞（RBCs）之间的相互作用，红细胞是纳米颗粒进入血液后可能的接触靶点。检测了50 - 2000 μmol/L稀土元素的溶血情况，以模拟其在医疗或职业暴露下的细胞毒性。我们发现，稀土元素暴露引起的溶血高度依赖于其浓度，细胞毒性顺序为La > Gd > Yb。稀土离子（REIs）的细胞毒性高于稀土氧化物（REOs），而纳米级REO比微米级REO引起更多的溶血。活性氧（ROS）的产生、ROS淬灭实验以及脂质过氧化检测证实，稀土元素通过与ROS相关的化学氧化作用导致细胞膜破裂。此外，我们发现稀土元素上蛋白质冠层的形成增加了稀土元素与细胞膜之间的空间排斥力，从而减轻了稀土元素的细胞毒性。理论模拟表明稀土元素与磷脂和蛋白质之间存在良好的相互作用。因此，我们的研究结果为稀土元素进入生物体血液循环系统后对红细胞产生细胞毒性提供了一个机制解释。
