Impatto delle microplastiche e dei contaminanti associati sugli epatociti: focus sugli aspetti metabolici in vitro

Microplastics (MPs), plastic particles with a diameter of less than 5 mm, have become ubiquitous environmental contaminants. They accumulate in the environment and enter the food chain, directly affecting human health. Moreover, they have been identified as carriers of other pollutants, leading to unpredictable health consequences. While this issue has raised concerns, our understanding of the toxicity, bioaccumulation, and interactions of MPs with other environmental pollutants remains limited. This study aimed to assess the impact, in vitro, of MPs on cell survival and lipid metabolism, both individually and in combination with two other environmental pollutants: bisphenol A (BPA), a chemical compound primarily used in the manufacturing of various plastics with well-known endocrine-disrupting properties, and cadmium (Cd), a heavy metal. Given that dietary intake is the primary route of human exposure to these contaminants. These substances can accumulate in the liver, making it a significant target for their harmful effects. We aimed at highlighting the effects of contaminants on hepatocytes, in vitro, and to identify the specific metabolic pathways affected. To achieve this objective, we exposed HepG2 cells, a human hepatoma-derived cell line, to various concentrations of BPA, Cd, and pristine or functionalized polystyrene MPs with diameters of 5 µm or 500 nm. We also exposed the cells to combinations of MPs and pollutants for different durations and under different cellular conditions and states. Cd exhibited the highest cytotoxicity among the three pollutants, showing dose-dependent adverse effects on both cell survival and intracellular lipid content. These effects were further exacerbated under conditions of nutrient deprivation, emphasizing the significance of metabolic state in the cellular response to pollutants. The employment of resveratrol (RV), a substance of natural origin could mitigate these harmful effects reducing the activation of programmed cell death mechanisms. BPA, on the other hand, exhibited endocrine-disrupting effects primarily in steatotic cells, where it increased intracellular lipid content after a 24-hour exposure. This underscores the vulnerability of lipid metabolism to BPA-induced disruptions. Interestingly, MPs displayed size- and dose-dependent internalization capacity but did not directly induce cytotoxicity or modulation of intracellular lipid content, regardless of their surface functionalization or dose. However, their significant role as carriers of pollutants cannot be underestimated. MPs have the capacity to influence the individual effects and bioavailability of associated contaminants when adsorbed onto their surfaces. The findings of this study underscore the significant impact of environmental pollutants on liver function and their potential contribution to the development of liver diseases. They emphasize the urgent necessity for additional research into the complex interplay of environmental pollutants, the conditions conducive to pollutant-pollutant interactions, and the resulting implications for human health, particularly in terms of cumulative and damaging effects. A comprehensive understanding of the effects of pollutants on the liver can help identify toxic and subtoxic doses and the specific metabolic pathways affected. This knowledge serves as a foundation for future research focusing on the modulation of specific molecules within these pathways.