Abstract

Background:

Understanding the epidemic of chronic kidney disease of uncertain etiology may be critical for health policies and public health responses. Recent studies have shown that microplastics (MPs) contaminate our food chain and accumulate in the gut, liver, kidney, muscle, and so on. Humans manufacture many plastics-related products. Previous studies have indicated that particles of these products have several effects on the gut and liver. Polystyrene (PS)-MPs (PS-MPs) induce several responses, such as oxidative stress, and affect living organisms.

Objectives:

The aim of this study was to investigate the effects of PS-MPs in kidney cells in vitro and in vivo.

Methods:

PS-MPs were evaluated in human kidney proximal tubular epithelial cells (HK-2 cells) and male C57BL/6 mice. Mitochondrial reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, inflammation, and autophagy were analyzed in kidney cells. In vivo, we evaluated biomarkers of kidney function, kidney ultrastructure, muscle mass, and grip strength, and urine protein levels, as well as the accumulation of PS-MPs in the kidney tissue.

Results:

Uptake of PS-MPs at different concentrations by HK-2 cells resulted in higher levels of mitochondrial ROS and the mitochondrial protein Bad. Cells exposed to PS-MPs had higher ER stress and markers of inflammation. MitoTEMPO, which is a mitochondrial ROS antioxidant, mitigated the higher levels of mitochondrial ROS, Bad, ER stress, and specific autophagy-related proteins seen with PS-MP exposure. Furthermore, cells exposed to PS-MPs had higher protein levels of LC3 and Beclin 1. PS-MPs also had changes in phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase B (AKT)/mitogen-activated protein kinase (mTOR) signaling pathways. In an in vivo study, PS-MPs accumulated and the treated mice had more histopathological lesions in the kidneys and higher levels of ER stress, inflammatory markers, and autophagy-related proteins in the kidneys after PS-MPs treatment by oral gavage.

Conclusions:

The results suggest that PS-MPs caused mitochondrial dysfunction, ER stress, inflammation, and autophagy in kidney cells and accumulated in HK-2 cells and in the kidneys of mice. These results suggest that long-term PS-MPs exposure may be a risk factor for kidney health. https://doi.org/10.1289/EHP7612

中文翻译：

---

聚苯乙烯微塑料对人肾近端小管上皮细胞 HK-2 和雄性 C57BL/6 小鼠的肾脏相关影响

摘要

背景：

了解病因不明的慢性肾病的流行可能对卫生政策和公共卫生反应至关重要。最近的研究表明，微塑料 (MPs) 会污染我们的食物链，并在肠道、肝脏、肾脏、肌肉等中积累。人类制造了许多与塑料相关的产品。先前的研究表明，这些产品的颗粒对肠道和肝脏有多种影响。聚苯乙烯 (PS)-MPs (PS-MPs) 诱导多种反应，例如氧化应激，并影响生物体。

目标：

本研究的目的是研究 PS-MPs在体外和体内对肾细胞的影响。

方法：

PS-MP 在人肾近端肾小管上皮细胞（HK-2 细胞）和雄性 C57BL/6 小鼠中进行了评估。在肾细胞中分析线粒体活性氧 (ROS)、内质网 (ER) 应激、炎症和自噬。在体内，我们评估了肾功能、肾脏超微结构、肌肉质量和握力、尿蛋白水平以及肾组织中 PS-MP 的积累的生物标志物。

结果：

HK-2 细胞摄取不同浓度的 PS-MP 导致更高水平的线粒体 ROS 和线粒体蛋白 Bad。暴露于 PS-MP 的细胞具有更高的内质网应激和炎症标志物。MitoTEMPO 是一种线粒体 ROS 抗氧化剂，可减轻 PS-MP 暴露时出现的更高水平的线粒体 ROS、Bad、ER 应激和特定的自噬相关蛋白。此外，暴露于 PS-MPs 的细胞具有更高的 LC3 和 Beclin 1 蛋白水平。 PS-MPs 也有丝裂原活化蛋白激酶 (MAPK) 和蛋白激酶 B (AKT)/丝裂原活化蛋白激酶 (mTOR) 的磷酸化变化) 信号通路。在体内 在一项研究中，PS-MPs 积累，并且经口强饲 PS-MPs 治疗后，经治疗的小鼠肾脏中有更多的组织病理学病变，肾脏中的内质网应激、炎症标志物和自噬相关蛋白水平更高。

结论：

结果表明，PS-MPs 在肾细胞中引起线粒体功能障碍、ER 应激、炎症和自噬，并在 HK-2 细胞和小鼠肾脏中积累。这些结果表明长期接触 PS-MP 可能是肾脏健康的一个危险因素。https://doi.org/10.1289/EHP7612