Xuan Lihui, Luo Jinhua, Qu Can, Guo Peiyu, Yi Wensen, Yang Jingjing, Yan Yuhui, Guan Hua, Zhou Pingkun, Huang Ruixue
Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan Province 410078, China.
Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan Province 410078, China.
Sci Total Environ. 2024 Feb 25;913:169606. doi: 10.1016/j.scitotenv.2023.169606. Epub 2023 Dec 28.
Nanoplastic particles are pervasive environmental contaminants with potential health risks, while mouse intestinal organoids provide accurate in vitro models for studying these interactions. Metabolomics, especially through LC-MS, enables detailed cellular response studies, and there's a novel interest in comparing metabolic changes across nanoparticle species using gut organoids. This study used a mouse intestinal organoid combined with cell model to explore the differences in metabolites and toxicity mechanisms induced by exposure to three nanoplastics (PS, PTFE, and PMMA). The results showed that PS, PTFE, and PMMA exposure reduced mitochondrial membrane potential, intracellular ROS accumulation and oxidative stress, and inhibited the AKT/mTOR signaling pathway. Non-targeted metabolomics results confirmed that three types of nanoplastic particles regulate cellular status by regulating fatty acid metabolism, nucleotide metabolism, necroptosis and autophagy pathways. More importantly, these representative metabolites were further validated in model groups after mouse intestinal organoids and HCT116 cells were exposed to the respective NPs, indicating that organoid metabolomics results can be used to effectively predict toxicity. Untargeted metabolomics is sensitive enough to detect subtle metabolomic changes when functional cellular analysis shows no significant differences. Overall, our study reveals the underlying metabolic mechanism of NPs-induced intestinal organoid toxicity and provides new insights into the possible adverse consequences of NPs.
纳米塑料颗粒是普遍存在的环境污染物，具有潜在的健康风险，而小鼠肠道类器官为研究这些相互作用提供了精确的体外模型。代谢组学，尤其是通过液相色谱-质谱联用技术，能够进行详细的细胞反应研究，并且人们对使用肠道类器官比较不同纳米颗粒种类的代谢变化产生了新的兴趣。本研究使用小鼠肠道类器官结合细胞模型，探讨暴露于三种纳米塑料（聚苯乙烯、聚四氟乙烯和聚甲基丙烯酸甲酯）所诱导的代谢物差异和毒性机制。结果表明，暴露于聚苯乙烯、聚四氟乙烯和聚甲基丙烯酸甲酯会降低线粒体膜电位、细胞内活性氧积累和氧化应激，并抑制AKT/mTOR信号通路。非靶向代谢组学结果证实，三种类型的纳米塑料颗粒通过调节脂肪酸代谢、核苷酸代谢、坏死性凋亡和自噬途径来调节细胞状态。更重要的是，在小鼠肠道类器官和HCT116细胞暴露于各自的纳米颗粒后，这些代表性代谢物在模型组中得到了进一步验证，表明类器官代谢组学结果可用于有效预测毒性。当功能细胞分析显示无显著差异时，非靶向代谢组学足够灵敏以检测细微的代谢组学变化。总体而言,我们的研究揭示了纳米颗粒诱导肠道类器官毒性的潜在代谢机制，并为纳米颗粒可能产生的不良后果提供了新的见解。
