Metabolite correlation permutation after mice acute exposure to PM2.5: Holistic exploration of toxicometabolomics by network analysis,Environmental Pollution

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Metabolite correlation permutation after mice acute exposure to PM2.5: Holistic exploration of toxicometabolomics by network analysis
Environmental Pollution ( IF 7.6 ) Pub Date : 2024-05-08 , DOI: 10.1016/j.envpol.2024.124128
Hao Chang ₁ , Xi Zhang ₂ , Zhonghua Lu ₁ , Biling Gao ₁ , Heqing Shen ₃

Affiliation

Many environmental toxicants can cause systemic effects, such as fine particulate matter (PM), which can penetrate the respiratory barrier and induce effects in multiple tissues. Although metabolomics has been used to identify biomarkers for PM, its multi-tissue toxicology has not yet been explored holistically. Our objective is to explore PM induced metabolic alterations and unveil the intra-tissue responses along with inter-tissue communicational effects. In this study, following a single intratracheal instillation of multiple doses (0, 25, and 150 μg as the control, low, and high dose), non-targeted metabolomics was employed to evaluate the metabolic impact of PM across multiple tissues. PM induced tissue-specific and dose-dependent disturbances of metabolites and their pathways. The remarkable increase of both intra- and inter-tissue correlations was observed, with emphasis on the metabolism connectivity among lung, spleen, and heart; the tissues’ functional specificity has marked their toxic modes. Beyond the inter-status comparison of the metabolite fold-changes, the current correlation network built on intra-status can offer additional insights into how the multiple tissues and their metabolites coordinately change in response to external stimuli such as PM exposure.

中文翻译：

小鼠急性暴露于 PM2.5 后的代谢相关性排列：网络分析的毒代谢组学整体探索

许多环境毒物会引起全身性影响，例如细颗粒物 (PM)，它可以穿透呼吸屏障并对多个组织产生影响。尽管代谢组学已被用来识别 PM 的生物标志物，但其多组织毒理学尚未得到全面探索。我们的目标是探索 PM 诱导的代谢变化，并揭示组织内反应以及组织间通讯效应。在这项研究中，在单次气管内滴注多个剂量（0、25和150μg作为对照，低剂量和高剂量）后，采用非靶向代谢组学来评估PM对多个组织的代谢影响。 PM 会引起代谢物及其途径的组织特异性和剂量依赖性紊乱。观察到组织内和组织间相关性显着增加，重点是肺、脾和心脏之间的代谢连通性；这些组织的功能特异性标志着它们的毒性模式。除了代谢物倍数变化的状态间比较之外，当前建立在状态内的相关网络可以提供更多关于多个组织及其代谢物如何响应外部刺激（例如 PM 暴露）而协调变化的见解。

更新日期：2024-05-08

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