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Research Article
6 May 2021

The Kidney-Related Effects of Polystyrene Microplastics on Human Kidney Proximal Tubular Epithelial Cells HK-2 and Male C57BL/6 Mice

Authors: Yung-Li Wang, Yu-Hsuan Lee, Yung-Ho Hsu, I-Jen Chiu, Cathy Chia-Yu Huang, Chih-Chia Huang, Zi-Chun Chia, Chung-Pei Lee, Yuh-Feng Lin, and Hui-Wen ChiuAuthors Info & Affiliations
Publication: Environmental Health Perspectives
Volume 129, Issue 5
CID: 057003
https://doi.org/10.1289/EHP7612
PDF

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

Supplementary Material

File (ehp7612.smcontents.508.pdf)
File (ehp7612.s001.acco.pdf)

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Published In

Environmental Health Perspectives
Volume 129 • Issue 5 • May 2021
PubMed: 33956507

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EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.

History

Received: 4 June 2020
Revision received: 19 March 2021
Accepted: 12 April 2021
Published online: 6 May 2021

Authors

Affiliations

Yung-Li Wang*
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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Yu-Hsuan Lee
Department of Cosmeceutics, China Medical University, Taichung, Taiwan
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Yung-Ho Hsu
Division of Nephrology, Department of Internal Medicine, Hsin Kuo Min Hospital, Taipei Medical University, Taoyuan City, Taiwan
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
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I-Jen Chiu
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
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Cathy Chia-Yu Huang
Department of Life Sciences, National Central University, Taoyuan City, Taiwan
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Chih-Chia Huang
Department of Photonics, Center of Applied Nanomedicine, National Cheng Kung University, Tainan, Taiwan
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Zi-Chun Chia
Department of Photonics, Center of Applied Nanomedicine, National Cheng Kung University, Tainan, Taiwan
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Chung-Pei Lee
School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
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Yuh-Feng Lin*
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
Department of Internal Medicine, School of Medicine, National Defense Medical Center, Taipei, Taiwan
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Hui-Wen Chiu
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
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Notes

Address correspondence to Hui-Wen Chiu, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250 Wuxing St., Taipei, Taiwan 110. Telephone: 886-2-22490088, ext. 8884. Email: [email protected]

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