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聚苯乙烯微塑料对老年小鼠的肝毒性:关注胃肠道转化和 AMPK/FoxO 通路的作用。

Hepatotoxic of polystyrene microplastics in aged mice: Focus on the role of gastrointestinal transformation and AMPK/FoxO pathway.

机构信息

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471003, China.

Northwest Institute of Plateau Biology Chinese Academy of Sciences, Xining, Qinghai 810008, China.

出版信息

Sci Total Environ. 2024 Mar 20;917:170471. doi: 10.1016/j.scitotenv.2024.170471. Epub 2024 Feb 1.

DOI:10.1016/j.scitotenv.2024.170471
PMID:38296072
Abstract

Microplastic (MP) toxicity has attracted widespread attention, whereas before triggering hepatotoxicity, ingested MPs first undergo transportation and digestion processes in the gastrointestinal tract, possibly interacting with the gastrointestinal contents (GIC). More alarming is the need for more understanding of how this process may impact the liver health of aged animals. This study selected old mice. Firstly, we incubated polystyrene microplastics (PS-MPs, 1 μm) with GIC extract. The results of SEM/EDS indicated a structural alteration in PS-MPs. Additionally, impurities resembling corona, rich in heteroatoms (O, N, and S), were observed. This resulted in an enhanced aggregating phenomenon of MPs. We conducted a 10-day experiment exposing aged mice to four concentrations of PS-MPs, ranging from 1 × 10 to 1 × 10 particles/L. Subsequent measurements of tissue pathology and body and organ weights were conducted, revealing alterations in liver structure. In the liver, 12 crucial metabolites were found by LC-MS technology, including purines, lipids, and amino acids. The AMPK/FoxO pathway was enriched, activated, and validated in western blotting results. We also comprehensively examined the innate immune system, inflammatory factors, and oxidative stress indicators. The results indicated decreased C3 levels, stable C4 levels, inflammatory factors (IL-6 and IL-8), and antioxidant enzymes were increased to varying degrees. PS-MPs also caused DNA oxidative damage. These toxic effects exhibited a specific dose dependence. Overall, after the formation of the gastrointestinal corona, PS-MPs subsequently impact various cellular processes, such as cycle arrest (p21), leading to hepatic and health crises in the elderly. The presence of gastrointestinal coronas also underscores the MPs' morphology and characteristics, which should be distinguished after ingestion.

摘要

微塑料(MP)毒性引起了广泛关注,然而,在引发肝毒性之前,摄入的 MPs 首先在胃肠道中经历运输和消化过程,可能与胃肠道内容物(GIC)相互作用。更令人担忧的是,需要更多地了解这一过程如何影响老年动物的肝脏健康。本研究选择了老年小鼠。首先,我们将聚苯乙烯微塑料(PS-MPs,1μm)与 GIC 提取物孵育。SEM/EDS 的结果表明 PS-MPs 的结构发生了改变。此外,观察到类似于冠状物的杂质,富含杂原子(O、N 和 S),这导致 MPs 的聚集现象增强。我们进行了一项为期 10 天的实验,使老年小鼠暴露于四个浓度的 PS-MPs 中,范围从 1×10 到 1×10 个粒子/L。随后测量了组织病理学和身体及器官重量,发现肝脏结构发生了变化。通过 LC-MS 技术,在肝脏中发现了 12 种关键代谢物,包括嘌呤、脂质和氨基酸。AMPK/FoxO 通路在 Western blot 结果中被富集、激活和验证。我们还全面检查了固有免疫系统、炎症因子和氧化应激指标。结果表明 C3 水平降低,C4 水平稳定,炎症因子(IL-6 和 IL-8)和抗氧化酶不同程度增加。PS-MPs 还导致 DNA 氧化损伤。这些毒性作用表现出特定的剂量依赖性。总体而言,在形成胃肠道冠状物后,PS-MPs 随后会对各种细胞过程产生影响,如周期停滞(p21),导致老年人的肝脏和健康危机。胃肠道冠状物的存在也强调了 MPs 形态和特征,在摄入后应加以区分。

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