Chronic environmental exposure to polystyrene microplastics increases the risk of nonalcoholic fatty liver disease.

Microplastics (MPs), as the crucial environmental pollutants, can be easily transported into the human body and accumulate in the liver. However, current studies mainly focus on acute exposure to MPs, investigations on long-term interactions with MPs alone remain limited. Thereby, we examined noxious properties of MPs and selected the most common polystyrene (PS) MPs as the research object, including unmodified PS MPs (PS-MPs) and positive-charged PS MPs (PS-NH) at 10 mg/L employing oral drinking water methods in mice for six consecutive months in vivo. In vitro, we treated the human hepatocyte cells with MPs at 25 μg/mL to explore involved mechanisms. The results revealed that six-month MPs exposure led to nonalcoholic fatty liver disease (NAFLD) including impaired liver functions, extensive lipid depositions accompanied by abnormal levels of metabolic genes and PS-NH MPs exerted a stronger effect than PS-MPs. Concurrently, mice treated with MPs revealed the accumulation of senescent hepatocytes, leading to increased secretions of senescent phenotypes in the liver. We also discovered that MPs initiated the HO-1/Nrf2 axis consequently inducing ferroptosis in vivo and in vitro, as shown by massive iron deposition, extensive lipid peroxidation along with significant protein expressions in ferroptosis-related markers. Additionally, targeting the HO-1/Nrf2 pathway to further alleviate ferroptosis with corresponding inhibitors could efficiently alleviate cell senescence. Therefore, our study reveals new evidence of the relationship between chronic exposure to MPs and NAFLD and furthers the understanding of how plastic pollution affects human health.