Neodymium nitrate promotes the apoptosis of mouse liver cells via Bcl2l1/Caspase 3 pathway.

IF 3.2 4区医学 Q1 Pharmacology, Toxicology and Pharmaceutics

Toxicology Mechanisms and Methods Pub Date : 2025-05-07 DOI:10.1080/15376516.2025.2501253

Jing Leng, Ning Wang, Xiu-Li Chang, Xiao-Peng Zhang, Jing Xu, Zheng-Li Yang, Ke-Lei Qian, Zhi-Qing Zheng, Gong-Hua Tao, Xu-Dong Jia, Ping Xiao, Xin-Yu Hong

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引用次数: 0

Abstract

Background: 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(NO₃)₃), the predominant water-soluble neodymium species, exhibits marked bioavailability with particular hepatic tropism.

Objective: This study aims to investigate the effects of neodymium nitrate on apoptosis of mouse liver cells and its underlying molecular mechanisms.

Results: 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.

Conclusion: 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.

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硝酸钕通过Bcl2l1/Caspase 3途径促进小鼠肝细胞凋亡。

背景：钕作为一种战略性稀土元素（REE），已被证明具有生物蓄积性，并可通过吸入空气中的颗粒物、摄入受污染的食物/水以及皮肤从土壤基质中吸收渗透人体系统，最终引起多器官毒理学表现。然而，钕的肝毒理学特征及其病理生理机制仍不充分表征。硝酸钕（Nd(NO3)3）是主要的水溶性钕种，具有明显的生物利用度，具有特殊的肝亲和性。目的：探讨硝酸钕对小鼠肝细胞凋亡的影响及其分子机制。结果：梯度浓度硝酸钕作用于小鼠肝细胞系AML12。结果表明，硝酸钕抑制肝细胞增殖，诱导细胞凋亡，并呈剂量依赖关系。Western blotting和qRT-PCR结果显示，硝酸钕抑制Bcl2l1转录，激活Caspase 3蛋白水解。为了进一步探索分子机制，我们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Caspase 3的切割。结论：硝酸钕通过Bcl2l1/Caspase 3通路诱导小鼠肝细胞凋亡。然而，这一发现可能为修订稀土元素毒理学风险评估框架提供关键的机制证据，因此需要进一步的研究来证实这一观点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology Mechanisms and Methods 医学-毒理学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment.