Acute phase response following pulmonary exposure to soluble and insoluble metal oxide nanomaterials in mice.

IF 7.2 1区医学 Q1 TOXICOLOGY

Particle and Fibre Toxicology Pub Date : 2023-01-17 DOI:10.1186/s12989-023-00514-0

Claudia Torero Gutierrez, Charis Loizides, Iosif Hafez, Anders Brostrøm, Henrik Wolff, Józef Szarek, Trine Berthing, Alicja Mortensen, Keld Alstrup Jensen, Martin Roursgaard, Anne Thoustrup Saber, Peter Møller, George Biskos, Ulla Vogel

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引用次数: 6

Abstract

Background: Acute phase response (APR) is characterized by a change in concentration of different proteins, including C-reactive protein and serum amyloid A (SAA) that can be linked to both exposure to metal oxide nanomaterials and risk of cardiovascular diseases. In this study, we intratracheally exposed mice to ZnO, CuO, Al₂O₃, SnO₂ and TiO₂ and carbon black (Printex 90) nanomaterials with a wide range in phagolysosomal solubility. We subsequently assessed neutrophil numbers, protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, Saa3 and Saa1 mRNA levels in lung and liver tissue, respectively, and SAA3 and SAA1/2 in plasma. Endpoints were analyzed 1 and 28 days after exposure, including histopathology of lung and liver tissues.

Results: All nanomaterials induced pulmonary inflammation after 1 day, and exposure to ZnO, CuO, SnO₂, TiO₂ and Printex 90 increased Saa3 mRNA levels in lungs and Saa1 mRNA levels in liver. Additionally, CuO, SnO₂, TiO₂ and Printex 90 increased plasma levels of SAA3 and SAA1/2. Acute phase response was predicted by deposited surface area for insoluble metal oxides, 1 and 28 days post-exposure.

Conclusion: Soluble and insoluble metal oxides induced dose-dependent APR with different time dependency. Neutrophil influx, Saa3 mRNA levels in lung tissue and plasma SAA3 levels correlated across all studied nanomaterials, suggesting that these endpoints can be used as biomarkers of acute phase response and cardiovascular disease risk following exposure to soluble and insoluble particles.

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小鼠肺部暴露于可溶性和不溶性金属氧化物纳米材料后的急性期反应。

背景:急性期反应(APR)的特征是不同蛋白质的浓度变化，包括c反应蛋白和血清淀粉样蛋白a (SAA)，它们可能与暴露于金属氧化物纳米材料和心血管疾病的风险有关。在这项研究中，我们气管内暴露于具有广泛吞噬溶酶体溶解度的ZnO, CuO, Al2O3, SnO2, TiO2和炭黑(Printex 90)纳米材料中。随后，我们评估了支气管肺泡灌洗液中中性粒细胞数量、蛋白质和乳酸脱氢酶活性、肺和肝组织中Saa3和Saa1 mRNA水平以及血浆中Saa3和Saa1 /2水平。分析暴露后1天和28天的终点，包括肺和肝组织病理学。结果:1 d后，所有纳米材料均引起肺部炎症，暴露于ZnO、CuO、SnO2、TiO2和Printex 90后，肺部Saa3 mRNA水平和肝脏Saa1 mRNA水平均升高。此外，CuO、SnO2、TiO2和Printex 90可提高血浆SAA3和SAA1/2水平。急性期反应可通过暴露后1天和28天不溶性金属氧化物的沉积表面积来预测。结论:可溶性和不溶性金属氧化物诱导APR呈剂量依赖性，且时间依赖性不同。中性粒细胞内流、肺组织中Saa3 mRNA水平和血浆Saa3水平在所有研究的纳米材料中都存在相关性，这表明这些终点可以用作暴露于可溶性和不溶性颗粒后急性期反应和心血管疾病风险的生物标志物。

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

Particle and Fibre Toxicology TOXICOLOGY-

CiteScore

15.90

自引率

4.00%

发文量

审稿时长

6 months

期刊介绍： Particle and Fibre Toxicology is an online journal that is open access and peer-reviewed. It covers a range of disciplines such as material science, biomaterials, and nanomedicine, focusing on the toxicological effects of particles and fibres. The journal serves as a platform for scientific debate and communication among toxicologists and scientists from different fields who work with particle and fibre materials. The main objective of the journal is to deepen our understanding of the physico-chemical properties of particles, their potential for human exposure, and the resulting biological effects. It also addresses regulatory issues related to particle exposure in workplaces and the general environment. Moreover, the journal recognizes that there are various situations where particles can pose a toxicological threat, such as the use of old materials in new applications or the introduction of new materials altogether. By encompassing all these disciplines, Particle and Fibre Toxicology provides a comprehensive source for research in this field.