Aluminium oxide nanoparticles (Al2O3-NPs) exposure impairs cardiovascular physiology and elevates health risk – proteomic and molecular mechanistic insights

IF 8.2 1区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Science of the Total Environment Pub Date : 2025-05-03 DOI:10.1016/j.scitotenv.2025.179576

Gobichettipalayam Balasubramaniam Maadurshni , Balamurali Mahalakshmi , Manikandan Nagarajan , Jeganathan Manivannan

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引用次数: 0

Abstract

The interactions of nanoparticles with biomolecules lead to toxicopathological outcomes through various mechanisms including oxidative stress. In this regard, the interplay of oxidative stress with other molecular mechanisms of cytotoxicity during aluminium oxide nanoparticles (Al₂O₃-NPs) induced cardiovascular toxicity was not yet precisely explored. Initially, the human serum protein interaction and its corona composition were explored through the gel/label-free proteomics (nLC-HRMS/MS) method. In addition, endothelial cells (EC) and cardiomyoblasts (CM) cultures were employed along with various oxidative stress and cell stress assays. Further, various expression studies (RT-qPCR, western blot, and immunofluorescence), kinase signalling, and siRNA mediated gene knockout assays were performed. Alongside, the in ovo impact on antioxidant enzymes and metabolomic pathways (¹H NMR) in the heart validated the role of oxidative stress during cardiotoxicity. The current outcome illustrates the dose-dependent increase of cytotoxicity and caspase (3 and 9) activation. The dose-dependent elevation and its synergy with cardiovascular stress signalling (ET-1 and Ang-II) illustrate the prominent role of oxidative stress during toxicity. In conclusion, the current study connects the role of the redox system and molecular stress pathways during Al₂O₃-NPs induced cardiotoxicity which extends the knowledge towards the precise health risk assessment during human exposure.

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氧化铝纳米颗粒（Al2O3-NPs）暴露损害心血管生理学和提高健康风险-蛋白质组学和分子机制见解

纳米颗粒与生物分子的相互作用通过包括氧化应激在内的各种机制导致毒性病理结果。在这方面，氧化应激与其他分子机制的细胞毒性在氧化铝纳米颗粒（Al2O3-NPs）诱导心血管毒性的相互作用尚未被精确探索。首先，通过凝胶/无标签蛋白质组学（nLC-HRMS/MS）方法探索人血清蛋白相互作用及其冠状组成。此外，内皮细胞（EC）和心肌细胞（CM）培养以及各种氧化应激和细胞应激试验。此外，还进行了各种表达研究（RT-qPCR、western blot和免疫荧光）、激酶信号传导和siRNA介导的基因敲除试验。此外，对心脏中抗氧化酶和代谢组学途径（1H NMR）的影响证实了氧化应激在心脏毒性中的作用。目前的结果说明了细胞毒性和半胱天冬酶（3和9）激活的剂量依赖性增加。剂量依赖性升高及其与心血管应激信号（ET-1和Ang-II）的协同作用说明氧化应激在毒性过程中的突出作用。总之，目前的研究将氧化还原系统和分子应激途径在Al2O3-NPs诱导的心脏毒性中的作用联系起来，从而扩展了对人体暴露时精确健康风险评估的认识。

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来源期刊

Science of the Total Environment 环境科学-环境科学

CiteScore

17.60

自引率

10.20%

发文量

8726

审稿时长

2.4 months

期刊介绍： The Science of the Total Environment is an international journal dedicated to scientific research on the environment and its interaction with humanity. It covers a wide range of disciplines and seeks to publish innovative, hypothesis-driven, and impactful research that explores the entire environment, including the atmosphere, lithosphere, hydrosphere, biosphere, and anthroposphere. The journal's updated Aims & Scope emphasizes the importance of interdisciplinary environmental research with broad impact. Priority is given to studies that advance fundamental understanding and explore the interconnectedness of multiple environmental spheres. Field studies are preferred, while laboratory experiments must demonstrate significant methodological advancements or mechanistic insights with direct relevance to the environment.