Chronic exposure to polystyrene microplastics induces renal fibrosis via ferroptosis.

With the increasing prevalence of microplastics (MPs) in the environment, human health has become a growing concern. After entering the human body, MPs accumulate in the kidneys, indicating that the kidneys are their major target organs. This study investigated nephrotoxicity associated with MPs, with a specific focus on polystyrene (PS) MPs and amino-functionalized polystyrene (PS-NH2) MPs. Although previous studies have documented the nephrotoxic effects associated with short-term exposure to MPs, the mechanisms of kidney toxicity caused by chronic long-term exposure to MPs remain largely unclear. In animal models, mice were exposed to MPs (10 mg/L) at concentrations that are accessible to humans, administered via drinking water over a period of six months. These findings indicate that MPs can induce renal fibrosis by facilitating the onset of inflammation and accumulation of a substantial number of inflammatory cells. Our in vitro study showed that long-term exposure to MPs (60 μg/mL) induced ferroptosis in renal tubular epithelial cells via ferritinophagy and secreted TGF-β1, leading to renal fibroblast activation. Conversely, the application of Fer-1, a ferroptosis inhibitor, prevents ferroptosis in renal epithelial cells and reverses the activation of renal fibroblasts. Our study identified a novel toxicity mechanism for renal fibrosis induced by MPs exposure, offering new insights into the detrimental effects of environmental MPs on human health.