Leng Jing, Wang Ning, Chang Xiu-Li, Zhang Xiao-Peng, Xu Jing, Yang Zheng-Li, Qian Ke-Lei, Zheng Zhi-Qing, Tao Gong-Hua, Jia Xu-Dong, Xiao Ping, Hong Xin-Yu
Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Toxicity Appraisal/National Key Laboratory of Environmental Health Impact Assessment of Environmental New Pollutants, Shanghai, China.
School of Public Health, Fudan University, Shanghai, China.
Toxicol Mech Methods. 2025 Jul 1:1-10. doi: 10.1080/15376516.2025.2501253.
Neodymium, as a strategic rare earth element (REE), has demonstrated bioaccumulative potential and can permeate human systems through inhalation of airborne particulates, ingestion of contaminated food/water, and dermal absorption from soil matrices, ultimately eliciting multi-organ toxicological manifestations. However, the hepatotoxicological profile of neodymium species and their pathophysiological mechanisms remain inadequately characterized. Neodymium nitrate (Nd(NO)), the predominant water-soluble neodymium species, exhibits marked bioavailability with particular hepatic tropism.
This study aims to investigate the effects of neodymium nitrate on apoptosis of mouse liver cells and its underlying molecular mechanisms.
Mouse liver cell line AML12 was treated with gradient concentrations of neodymium nitrate. The results showed that neodymium nitrate inhibited liver cell proliferation, induced apoptosis, and exhibited a dose-dependent relationship. Western blotting and quantitative real-time PCR (qRT-PCR) revealed that neodymium nitrate suppressed Bcl2l1 transcription and activated the proteolysis of Caspase 3. To further explore the molecular mechanism, Bcl2l1 protein was overexpressed in mouse liver cells. The findings indicated that overexpression of Bcl2l1 rescued neodymium nitrate-induced apoptotic phenotypes and attenuated Caspase 3 cleavage.
The present data suggest that neodymium nitrate induces apoptosis of mouse liver cells through the Bcl2l1/Caspase 3 pathway. However, further studies are called for to substantiate this view, as the findings may provide critical mechanistic evidence for revising the toxicological risk assessment frameworks of rare earth elements.
钕作为一种战略性稀土元素，已显示出生物累积潜力，可通过吸入空气中的颗粒物、摄入受污染的食物/水以及从土壤基质中经皮肤吸收进入人体系统，最终引发多器官毒理学表现。然而，钕物种的肝毒理学特征及其病理生理机制仍未得到充分表征。硝酸钕（Nd(NO)）是主要的水溶性钕物种，具有显著的生物利用度和特定的肝脏嗜性。
本研究旨在探讨硝酸钕对小鼠肝细胞凋亡的影响及其潜在的分子机制。
用梯度浓度的硝酸钕处理小鼠肝细胞系AML12。结果表明，硝酸钕抑制肝细胞增殖，诱导凋亡，且呈剂量依赖性关系。蛋白质免疫印迹法和定量实时聚合酶链反应（qRT-PCR）显示，硝酸钕抑制Bcl2l1转录并激活半胱天冬酶3的蛋白水解作用。为进一步探究分子机制，在小鼠肝细胞中过表达Bcl2l1蛋白。结果表明，Bcl2l1的过表达挽救了硝酸钕诱导的凋亡表型并减弱了半胱天冬酶3的切割。
目前的数据表明，硝酸钕通过Bcl2l/Caspase 3途径诱导小鼠肝细胞凋亡。然而，由于这些发现可能为修订稀土元素的毒理学风险评估框架提供关键的机制证据，因此需要进一步研究来证实这一观点。
