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解读钨酸盐和钼酸盐的毒性:对L929细胞代谢活性、氧化应激和遗传毒性的影响

Deciphering the Toxicity of Metal Tungstates and Molybdates: Effects on L929 Cell Metabolic Activity, Oxidative Stress, and Genotoxicity.

作者信息

Assis Marcelo, de Souza Amanda, Dos Santos Jorge Sousa Karolyne, Nina Diana Gabriela Nina, Bonfacio Mirian, Granito Renata Neves, Rennó Ana Claudia Muniz

机构信息

Department of Biosciences, Federal University of São Paulo (UNIFESP), Santos, SP, Brazil.

出版信息

J Appl Toxicol. 2025 Oct;45(10):2197-2216. doi: 10.1002/jat.4836. Epub 2025 Jun 22.

Abstract

The increasing development and application of metal-based materials in biomedical and environmental fields raise important concerns regarding their potential cytotoxic and genotoxic effects. Metal tungstates (MWO) and molybdates (MMoO) offer promising functional properties in health and environmental solutions but require safety validation before practical use. This study aimed to synthesize a series of these compounds based on Ag, Ca, Sr, and Zn and evaluate their behavior in both solid state and solution, focusing on their biological interactions with L929 fibroblast cells. Cell metabolic activity was assessed over 1, 3, and 7 days, revealing that Ag-based materials were toxic even at low concentrations (7.8 μg/mL), while Ca-, Sr-, and Zn-based compounds enhanced metabolic activity at lower doses. At concentrations above 62.5 μg/mL, Zn-based materials showed toxicity, accompanied by morphological cell alterations. ROS production emerged as the primary mechanism of toxicity, especially for Ag-based samples. Intracellular oxidative stress analysis confirmed elevated ROS and RNS levels over time. Apoptotic and necrotic pathways were identified only in α-AgWO at the lowest dose. The micronucleus assay showed genotoxic responses in Ag-based compounds comparable to positive controls, while other materials showed no significant genotoxicity. These findings indicate that Ca-, Sr-, and Zn-based tungstates and molybdates may be safely applied in biological contexts, whereas Ag-based materials, though effective, demand cautious use due to their long-term genotoxic potential.

摘要

金属基材料在生物医学和环境领域的不断发展与应用引发了人们对其潜在细胞毒性和基因毒性影响的重要关注。金属钨酸盐(MWO)和钼酸盐(MMoO)在健康和环境解决方案中具有良好的功能特性,但在实际应用前需要进行安全性验证。本研究旨在合成一系列基于银、钙、锶和锌的这些化合物,并评估它们在固态和溶液中的行为,重点关注它们与L929成纤维细胞的生物相互作用。在1天、3天和7天内评估细胞代谢活性,结果显示即使在低浓度(7.8μg/mL)下,银基材料也具有毒性,而钙基、锶基和锌基化合物在较低剂量下可增强代谢活性。在浓度高于62.5μg/mL时,锌基材料表现出毒性,并伴有细胞形态改变。活性氧(ROS)的产生是毒性的主要机制,尤其是对于银基样品。细胞内氧化应激分析证实,随着时间的推移,ROS和活性氮(RNS)水平升高。仅在最低剂量的α-AgWO中发现了凋亡和坏死途径。微核试验显示银基化合物的基因毒性反应与阳性对照相当,而其他材料未显示出明显的基因毒性。这些发现表明,钙基、锶基和锌基钨酸盐和钼酸盐可能可以安全地应用于生物环境中,而银基材料虽然有效,但由于其长期的基因毒性潜力,需要谨慎使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a16/12371800/3b19c6bbcd7b/JAT-45-2197-g007.jpg

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