UVB-aged polystyrene microplastics induce enhanced stress responses in human proximal tubular cells

Microplastics (MPs) are increasingly detected in human biological matrices, raising concerns about their potential systemic effects, including on the kidney. However, the cellular responses of renal tubular epithelium to MPs and the role of environmental aging processes in modulating their biological activity remain poorly defined. Under environmental conditions, MPs undergo photo-oxidative transformations that alter their surface chemistry and may influence their interactions with biological systems. In this study, we investigated the effects of 1µm polystyrene MPs in virgin (MPs_V) and UVB-oxidised (MPs_Ox) forms in a human renal proximal tubular cell line (HK-2). Cells were exposed to MPs (25 and 50µg/mL), and multiple endpoints related to cellular stress and genomic stability were evaluated, including lysosome-associated responses, oxidative damage, DNA integrity, micronucleus formation, DNA-content distribution profiles as an indirect proxy of proliferative status, and cytoskeletal organisation. Exposure to MPs induced measurable stress responses in tubular cells, with oxidised particles generally eliciting stronger effects than MPs_V. These responses were consistent with increased oxidative stress, lysosome-associated cellular responses, genomic instability-associated alterations, activation of stress-responsive molecular pathways, and cytoskeletal perturbation. Collectively, these findings indicate that environmentally aged polystyrene MPs elicit more evident cellular stress responses than their virgin counterparts in HK-2 cells. Our results highlight the importance of incorporating environmentally transformed MPs into toxicological testing frameworks to improve the biological relevance of hazard assessment.