Cytotoxic and dysmetabolic impact of polystyrene nanoplastics, a new potential atherosclerotic cardiovascular risk factor, on a steatosis model of HepG2 cells
Polystyrene nanoplastics and steatotic hepatocytes
Copyright (c) 2025 European Atherosclerosis Journal

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Published: April 30, 2025
Abstract
The widespread presence of nanoplastics (NPs) in the environment has recently raised concerns regarding the human health. More specifically, adverse effects related to NP exposure and potentially associated with the occurrence and progression of cardiometabolic diseases, including atherosclerotic cardiovascular disease (ASCVD) and metabolic dysfunction-associated steatotic liver disease (MASLD), are currently under investigation. To understand the toxic and dysmetabolic effects induced by NPs in the liver, a major player in cardiometabolic health, we aimed at characterizing the cytotoxic effects induced by polystyrene NPs (PS-NPs) of 500 nm in human hepatocarcinoma HepG2 cells. PS-NPs tested at concentrations of 10, 100, and 200 mg/mL reduced HepG2 cell viability. Intracellular PS-NP content increased according to exposure time and concentration. Moreover, exposure to 500 nm PS-NPs altered glucose uptake after 24 hour-NP exposure (200 mg/mL). This study may contribute to unveil the PS-NP involvement in the pathological mechanisms associated with liver diseases, including MASLD.
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References
- Thompson RC, Swan SH, Moore CJ, et al. Our plastic age. Philos Trans R Soc Lond B Biol Sci 2009; 364(1526):1973-6. https://doi.org/10.1098/rstb.2009.0054.
- Geyer R, Jambeck JR, et al. Production, use, and fate of all plastics ever made. Sci Adv 2017; 3:e1700782. https://doi.org/10.1126/sciadv.1700782.
- Jambeck JR, Geyer R, Wilcox C, et al. Plastic waste inputs from land into the ocean. Science 2015; 347:768–771. https://doi.org/10.1126/science.1260352.
- Zhang K, Hamidian AH, Tubić A, et al. Understanding plastic degradation and microplastic formation in the environment: A review. Environ Pollut 2021; 274:116554. https://doi.org/10.1016/j.envpol.2021.116554.
- Sangkham S, Faikhaw O, Munkong N, et al. A review on microplastics and nanoplastics in the environment: Their occurrence, exposure routes, toxic studies, and potential effects on human health. Mar Pollut Bull. 2022; 181:113832. https://doi.org/10.1016/j.marpolbul.2022.113832.
- Humboldt-Dachroeden S, Mantovani A. Assessing environmental factors within the one health approach. Medicina (Kaunas) 2021; 57:240. https://doi.org/10.3390/MEDICINA57030240.
- Leslie HA, van Velzen MJM, Brandsma SH, et al. Discovery and quantification of plastic particle pollution in human blood. Environ Int 2022. 163:107199. https://doi.org/10.1016/j.envint.2022.107199.
- Pironti C, Notarstefano V, Ricciardi M, et al. First Evidence of Microplastics in Human Urine, a Preliminary Study of Intake in the Human Body. Toxics 2023; 11:40. https://doi.org/10.3390/toxics11010040.
- Ragusa A, Notarstefano V, Svelato A, et al. Raman Microspectroscopy Detection and Characterisation of Microplastics in Human Breastmilk. Polymers (Basel) 2022; 14:2700. https://doi.org/10.3390/polym14132700.
- Hu CJ, Garcia MA, Nihart A, et al. Microplastic presence in dog and human testis and its potential association with sperm count and weights of testis and epididymis. Toxicological Sciences 2024; 200:235–240. https://doi.org/10.1093/toxsci/kfae060.
- Zeng L, Zhou C, Xu W, et al. The ovarian-related effects of polystyrene nanoplastics on human ovarian granulosa cells and female mice. Ecotoxicol Environ Saf 2023; 257:114941. https://doi.org/10.1016/j.ecoenv.2023.114941.
- Ragusa A, Svelato A, Santacroce C, et al. Plasticenta: First evidence of microplastics in human placenta. Environ Int. 2021; 146:106274. https://doi.org/10.1016/j.envint.2020.106274.
- Jenner LC, Rotchell JM, Bennett RT, et al. Detection of microplastics in human lung tissue using μFTIR spectroscopy. Sci Total Environ. 2022; 831:154907. https://doi.org/10.1016/j.scitotenv.2022.154907.
- Horvatits T, Tamminga M, Liu B, et al. Microplastics detected in cirrhotic liver tissue. EBioMedicine 2022; 82:104147. https://doi.org/10.1016/j.ebiom.2022.104147.
- Gopinath PM, Saranya V, Vijayakumar Set, et al. Assessment on interactive prospectives of nanoplastics with plasma proteins and the toxicological impacts of virgin, coronated and environmentally released-nanoplastics. Sci Rep 2019. 9: 8860. https://doi.org/10.1038/s41598-019-45139-6.
- Wan S, Wang X, Chen W, et al. Exposure to high dose of polystyrene nanoplastics causes trophoblast cell apoptosis and induces miscarriage. Part Fibre Toxicol. 2024; 21:13. https://doi.org/10.1186/s12989-024-00574-w.
- Lett Z, Hall A, Skidmore S, et al. Environmental microplastic and nanoplastic: Exposure routes and effects on coagulation and the cardiovascular system. Environ Pollut. 2021; 291:118190. https://doi.org/10.1016/j.envpol.2021.118190.
- Marfella R, Prattichizzo F, Sardu C, et al. Microplastics and Nanoplastics in Atheromas and Cardiovascular Events. New England Journal of Medicine 2024; 390:900–910. https://doi.org/10.1056/nejmoa2309822.
- Wang B, Liang B, Huang Y, et al. Long-Chain Acyl Carnitines Aggravate Polystyrene Nanoplastics-Induced Atherosclerosis by Upregulating MARCO. Advanced Science 2023; 10:2205876. https://doi.org/10.1002/advs.202205876.
- Florance I, Chandrasekaran N, Gopinath PM, et al. Exposure to polystyrene nanoplastics impairs lipid metabolism in human and murine macrophages in vitro. Ecotoxicol Environ Saf. 2022; 238:113612. https://doi.org/10.1016/j.ecoenv.2022.113612.
- Busch M, Bredeck G, Kämpfer AAM, et al. Investigations of acute effects of polystyrene and polyvinyl chloride micro- and nanoplastics in an advanced in vitro triple culture model of the healthy and inflamed intestine. Environ Res 2021; 193:110536. https://doi.org/10.1016/j.envres.2020.110536.
- Choi D, Bang J, Kim T, et al. In vitro chemical and physical toxicities of polystyrene microfragments in human-derived cells. J Hazard Mater 2020; 400:123308. https://doi.org/10.1016/j.jhazmat.2020.123308.
- Haldar S, Yhome N, Muralidaran Y, et al. Nanoplastics Toxicity Specific to Liver in Inducing Metabolic Dysfunction-A Comprehensive Review. Genes (Basel) 2023; 14:590. https://doi.org/10.3390/genes14030590.
- Auguet T, Bertran L, Barrientos-Riosalido A, et al. Are Ingested or Inhaled Microplastics Involved in Nonalcoholic Fatty Liver Disease? Int J Environ Res Public Health 2022; 19:13495. https://doi.org/10.3390/ijerph192013495.
- Pelegrini K, Pereira TCB, Maraschin TG, et al. Micro- and nanoplastic toxicity: A review on size, type, source, and test-organism implications. Sci Total Environ. 2023; 878:162954. https://doi.org/10.1016/j.scitotenv.2023.162954.
- Schröter L, Ventura N. Nanoplastic Toxicity: Insights and Challenges from Experimental Model Systems. Small 2022; 18:e2201680. https://doi.org/10.1002/smll.202201680.
- Lin S, Zhang H, Wang C, et al. Metabolomics Reveal Nanoplastic-Induced Mitochondrial Damage in Human Liver and Lung Cells. Environ Sci Technol. 2022; 56:12483-12493. https://doi.org/10.1021/acs.est.2c03980.
- Sun N, Shi H, Li X, et al. Combined toxicity of micro/nanoplastics loaded with environmental pollutants to organisms and cells: Role, effects, and mechanism. Environ Int. 2023; 171:107711. https://doi.org/10.1016/j.envint.2022.107711.
- Liu L, Xu K, Zhang B, et al. Cellular internalization and release of polystyrene microplastics and nanoplastics. Sci Total Environ. 2021; 779:146523. https://doi.org/10.1016/j.scitotenv.2021.146523.
- Han SW, Ryu KY. Increased clearance of non-biodegradable polystyrene nanoplastics by exocytosis through inhibition of retrograde intracellular transport. J Hazard Mater 2022; 439:129576. https://doi.org/10.1016/j.jhazmat.2022.129576.
- Brun NR, van Hage P, Hunting ER, et al. Polystyrene nanoplastics disrupt glucose metabolism and cortisol levels with a possible link to behavioural changes in larval zebrafish. Commun Biol 2019; 2:382. https://doi.org/10.1038/s42003-019-0629-6.
- Zhao J, Gomes D, Jin L, et al. Polystyrene bead ingestion promotes adiposity and cardiometabolic disease in mice. Ecotoxicol Environ Saf 2022; 232:113239. https://doi.org/10.1016/j.ecoenv.2022.113239.
- Lee SE, Yoon HK, Kim DY, et al. An Emerging Role of Micro- and Nanoplastics in Vascular Diseases. Diseases. Life (Basel) 2024; 14:255. https://doi.org/10.3390/life14020255.