DTPA and anti-inflammatory drug associations to alleviate Pu-induced response of macrophages in vitro

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2025-01-19 DOI:10.1016/j.tiv.2025.106007

Alexandra Bourgois , Guillaume Cosler , Diane Riccobono , Clélia Le Gallic , Sabine François , Anne Van der Meeren

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引用次数: 0

Abstract

Internal contamination by inhalation of plutonium poorly soluble compounds leads to their long time retention in alveolar macrophages inducing delayed pathology development. As previous studies highlighted co-localization of retained Pu and inflammatory lesions, this study was designed to assess the combined effect of the reference treatment (DTPA) and anti-inflammatory drugs on Pu-induced early response of macrophages in vitro.

Pu colloids, mimicking poorly soluble Pu, were characterized using filtration and solid-state nuclear track detectors CR39. Their bioavailability was determined using a biphasic acellular model. Treatment effects on Pu dissolution and release as well as on Pu-induced pro-inflammatory response were assessed over 7 days on macrophage-like cells.

DTPA treatment, associated or not with anti-inflammatory drug, increased Pu dissolution and release from contaminated THP-1 differentiated cells after 7 days. Significant decreases in Pu-induced IL-8 and MCP-1 secretions were also observed with anti-inflammatory treatment associated or not with DTPA.

This study highlighted the ability of DTPA to partially dissolve a poorly soluble form of Pu as well as the ability of anti-inflammatory drugs to modulate Pu-induced pro-inflammatory response in macrophage-like cells. These treatments seem a promising strategy to improve the clinical management of Pu pulmonary contaminations and to limit delayed pulmonary pathology occurrence.

Abstract Image

查看原文本刊更多论文

DTPA与抗炎药物联合减轻巨噬细胞pu诱导的体外反应。

吸入钚难溶性化合物的内部污染导致其在肺泡巨噬细胞中长时间滞留，从而导致病理发展延迟。鉴于既往研究强调残留Pu与炎性病变的共定位，本研究旨在评估参考治疗（DTPA）和抗炎药物联合使用对体外巨噬细胞Pu诱导的早期反应的影响。采用过滤和固体核径迹探测器CR39对模拟难溶性Pu的Pu胶体进行了表征。采用双相脱细胞模型测定其生物利用度。在7 天的巨噬细胞样细胞上评估治疗对Pu溶解和释放以及Pu诱导的促炎反应的影响。DTPA治疗，无论是否联合抗炎药物，在7 天后，污染的THP-1分化细胞中Pu的溶解和释放增加。与DTPA相关或不相关的抗炎治疗也观察到pu诱导的IL-8和MCP-1分泌显著降低。这项研究强调了DTPA部分溶解难溶性Pu的能力，以及抗炎药物调节巨噬细胞样细胞中Pu诱导的促炎反应的能力。这些治疗似乎是一种有希望的策略，以改善肺部污染的临床管理和限制延迟的肺部病理发生。

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 in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.