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

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.

Development and application of a health-based framework for informing regulatory action in relation to exposure of microplastic particles in California drinking water

“…These observations are consistent with results reporting the effects of MPs on gastric cells and the induction of pro-inflammatory cytokines such as IL-6 (e.g., Forte et al [ 40 ], Hwang et al [ 49 ]), biomarkers that have been shown to result in downstream Nf-κb activation (Brasier et al [ 13 ]). Several other in vitro studies provide additional lines-of-evidence linking exposure to MPs with a pattern of overall inflammation and reactive oxygen species production, similar to observations in live animal models (Wang et al [ 114 ]; Choi et al [ 21 ], Dong et al [ 32 ], Wu et al [ 123 ]; Efeoglu et al [ 34 ]). Although we emphasize the potential importance of these observations towards an improved mechanistic understanding of the adverse effects associated with MPs, we also note the need for additional research towards strengthening various QA/QC components of study design and implementation to enable better comparison and extrapolation of results between studies using different cell types and target organs and with a variety of different types of MPs, prior to reliably aligning to any MIEs.…”

“…More recently, a number of studies have reported the uptake of polystyrene spheres (2–20 μm) in the gut, liver, and kidney tissues of mice, with a number of adverse effects being observed and reported, including oxidative stress, altered metabolic profile and lipid metabolism, as well as chronic inflammation (Deng et al, [ 29 ], Jin et al, [ 55 ], Li et al, [ 64 ], Shengchen et al [ 99 ], Wang et al, [ 114 ], Xu et al [ 125 ], Zheng et al, [ 127 ]). Generally, a particle-size dependence influencing the uptake and presence of polystyrene spheres in various tissues resulting in a variety of adverse effects has been reported, with smaller particles (< 1 µm) understood to have a higher likelihood for translocation (e.g., Jani et al, [ 50 ], [ 51 ]).…”

Acute and Sub-Chronic Effects of Microplastics (3 and 10 µm) on the Human Intestinal Cells HT-29

“…Taken together, this means that the overall toxicity of MPs can be extremely variable. Studies specifically designed to assess the health risk of mixtures of different vehicles and adsorbed xenobiotics are still poor because most of the uptake data on MPs have been obtained from mammalian studies that use virgin polystyrene (PS) MPs in in vivo and in vitro models [ 27 , 28 , 29 , 30 , 31 , 32 ]. After oral ingestion, MPs can cross the intestinal barrier and reach the systemic circulation.…”

Factors affecting zero-waste behaviors: Focusing on the health effects of microplastics

“…However, such education should be based on empirical studies of microplastics and its health risk. Animal experiments and studies have proven the risk of microplastics in other organisms [31][32]; however, no study has confirmed the health hazards in humans. This is because studies on the environment and its health effects are extensive, and the health risk appears over the long-term rather than the short-term.…”