Polystyrene microplastics induce hepatotoxicity and disrupt lipid metabolism in the liver organoids

Cheng, Wei; Li, Xiaolan; Zhou, Yue; Yu, Hengyi; Xie, Yichun; Guo, Huaqi; Wang, Hui; Li, Yan; Feng, Yuanming; Wang, Yan

doi:10.1016/j.scitotenv.2021.150328

Cited by 145 publications

(72 citation statements)

References 81 publications

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“…Taken together, the hepatotoxicity of MPs, TBBPA, and MPTA at environmental concentrations was tolerable in N_DOs, suggesting that MPs and TBBPA are safe for healthy individuals. These results are distinct from the study mentioned above with human embryonic stem cell-derived hepatocyte organoids with dynamic exposure, which showed cytotoxicity, lipid metabolism, and related gene transcriptional toxicity at even lower concentrations of 250 ng/mL 10 . We reasoned that hydrogel encapsulation and multicellular constituents probably altered the toxic response, and second, static exposure in this study reduced the physical damage by particles.…”

Section: The Mp-tbbpa Complex Had Little Toxicity To Healthy Human-de...contrasting

confidence: 99%

“…Multicellular organoids developed from human pluripotent stem cells can recapitulate tissue structure and multifaceted functions by re-establishing heterogeneous cell-cell interactions and are regarded as advanced alternatives in disease modeling, drug screening and autologous therapy 9 . Recently, a milestone report on human embryonic stem cell-derived hepatocyte organoids revealed the toxicology of 1 μm polystyrene MPs by disrupting liver lipid metabolism 10 . Human induced pluripotent stem cells (hiPSCs) carry genetic inheritance of individuals 9 ; thus, hiPSC-derived organoids are potent in personalized environmental toxicology.…”

Section: Introductionmentioning

confidence: 99%

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Toxicity of microplastics and plastic additive co-exposure in liver Disse organoids from healthy donors and patient-derived induced pluripotent stem cells

Liang

Luo

et al. 2022

Preprint

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The ubiquitous microplastics (MPs) and plastic additives in the environment usually form complexes, enter human blood circulation, and increase the risk of steatohepatitis. The liver Disse space plays a vital role in corresponding hepatic pathological processes. However, due to the limited understanding of the regulatory cues in multilineage maturation, the generation of large-scale Disse-like organoids (DOs) mirroring the comprehensive toxicity responses of MPs is challenging. Here, using human-induced pluripotent stem cells (hiPSCs), we biofabricated healthy donors and patient-derived DOs containing hepatocytes, endothelial cells, and hepatic stellate cells, resembling the features of Disse space. These organoids revealed that polystyrene MPs preferentially entered endothelial cells and then dispersed throughout the organoids, similar to reported studies in zebrafish. Co-exposure to MPs and tetrabromobisphenol A (TBBPA), a common plastic additive, showed enhanced accumulation of contamination in the organoids. We also biofabricated alcoholic liver disease (ALD) patient-derived DOs representing the specific disease transcriptional profiles. We found that co-exposure to MPs and TBBPA at environmental-related dosages significantly elevated the pathological transcriptional expression and biochemical profiles in patient-derived DOs but not in healthy organoids, suggesting that both hereditary factors and pollutants contribute to susceptibility to environmental toxicants. This study exemplified the value of biofabricated hiPSC-derived organoids in environmental toxicology and offered a powerful strategy for personalized toxicology evaluation.

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Section: The Mp-tbbpa Complex Had Little Toxicity To Healthy Human-de...contrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Toxicity of microplastics and plastic additive co-exposure in liver Disse organoids from healthy donors and patient-derived induced pluripotent stem cells

Liang

Luo

et al. 2022

Preprint

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“…Abnormal lipid metabolism is common in hepatotoxicity and even acts as a marker of liver injury (Huang et al, 2020 ; Cheng et al, 2022 ). Glycerol is a small molecule that is an important intermediate between carbohydrate and lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Gynura segetum root extract (GSrE) induced hepatotoxicity based on metabolomic signatures and microbial community profiling in rats

Li²,

Lu³

et al. 2022

Front. Microbiol.

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In recent years, many reports focus on the hepatotoxicity of Gynura segetum root extract (GSrE), but the interaction between GSrE and the gut microbiota is still unclear. This study investigated the mechanism of GSrE-induced hepatotoxicity of different doses and exposure durations by combining metabolomics and gut microbiota analysis. SD rats were divided into 3 groups: blank, low-dose (7.5 g/kg), and high-dose (15 g/kg) groups. Urine and feces samples were collected on day 0, day 10, and day 21. Metabolomics based on gas chromatography-mass spectrometry (GC-MS) was carried out to identify metabolites and metabolic pathways. 16S rDNA gene sequencing was applied to investigate the composition of gut microbiota before and after GSrE-induced hepatotoxicity. Finally, a correlation analysis of metabolites and gut microbiota was performed. Differential metabolites in urine and feces involved amino acids, carbohydrates, lipids, organic acids, and short chain fatty acids. Among them, L-valine, L-proline, DL-arabinose, pentanoic acid, D-allose, and D-glucose in urine and D-lactic acid and glycerol in fecal metabolites depended on the exposure of time and dose. In addition, 16S rDNA sequencing analysis revealed that GSrE-induced hepatotoxicity significantly altered the composition of gut microbiota, namely, f_Muribaculaceae_Unclassified, Lactobacillus, Bacteroides, Lachnospiraceae_NK4A136_group, f_Ruminococcaceae_Unclassified, Prevotellaceae_Ga6A1_group, and Escherichia-Shigella. The correlation analysis between gut microbiota and differential metabolites showed the crosstalk between the gut microbiota and metabolism in host involving energy, lipid, and amino acid metabolisms. In summary, our findings revealed that peripheral metabolism and gut microbiota disorders were time- and dose-related and the correlation between gut microbiota and metabolites in GSrE-induced hepatotoxicity.

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“… 55 − 57 However, information about the effects of microplastics on kidney and liver cells is limited. 58 , 59 Understanding the effects of microplastics on human kidney and liver cells is of the utmost importance to better understand the potential risks to human health. This study was conducted using a human kidney cell line and a human liver cell line to simultaneously study the effects of microplastics in vitro.…”

Section: Introductionmentioning

confidence: 99%

Effects of Polystyrene Microplastics on Human Kidney and Liver Cell Morphology, Cellular Proliferation, and Metabolism

2022

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Microplastics have gained much attention due to their prevalence and abundance in our everyday lives. They have been detected in household items such as sugar, salt, honey, seafood, tap water, water bottles, and food items wrapped in plastic. Once ingested, these tiny particles can travel to internal organs such as the kidney and liver and cause adverse effects on the cellular level. Here, human embryonic kidney (HEK 293) cells and human hepatocellular (Hep G2) liver cells were used to examine the potential toxicological effects of 1 μm polystyrene microplastics (PS-MPs). Exposing cells to PS-MPs caused a major reduction in cellular proliferation but no significant decrease in cell viability as determined by the trypan blue assay in both cell lines. Cell viability remained at least 94% for both cell lines even at the highest concentration of 100 μg/mL of PS-MPs. Phase-contrast imaging of both kidney and liver cells exposed to PS-MPs at 72 h showed significant morphological changes and uptake of PS-MP particles. Confocal fluorescent microscopy confirmed the uptake of 1 μm PS-MPs at 72 h for both cell lines. Additionally, flow cytometry experiments verified that more than 70% of cells internalized 1 μm PS-MPs after 48 h of exposure for both kidney and liver cells. Reactive oxygen species (ROS) studies revealed kidney and liver cells exposed to PS-MPs had increased levels of ROS at each concentration and for every time point tested. Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis at 24 and 72 h revealed that both HEK 293 and Hep G2 cells exposed to PS-MPs lowered the gene expression levels of the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ), and antioxidant enzymes superoxide dismutase 2 ( SOD2 ) and catalase ( CAT ), thus reducing the potential of SOD2 and CAT to detoxify ROS. These adverse effects of PS-MPs on human kidney and liver cells suggest that ingesting microplastics may lead to toxicological problems on cell metabolism and cell–cell interactions. Because exposing human kidney and liver cells to microplastics results in morphological, metabolic, proliferative changes and cellular stress, these results indicate the potential undesirable effects of microplastics on human health.

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Polystyrene microplastics induce hepatotoxicity and disrupt lipid metabolism in the liver organoids

Cited by 145 publications

References 81 publications

Toxicity of microplastics and plastic additive co-exposure in liver Disse organoids from healthy donors and patient-derived induced pluripotent stem cells

Toxicity of microplastics and plastic additive co-exposure in liver Disse organoids from healthy donors and patient-derived induced pluripotent stem cells

Investigation of Gynura segetum root extract (GSrE) induced hepatotoxicity based on metabolomic signatures and microbial community profiling in rats

Effects of Polystyrene Microplastics on Human Kidney and Liver Cell Morphology, Cellular Proliferation, and Metabolism

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