Perfluorooctane sulfonate (PFOS) causes aging damage in the liver through the mt-DNA-mediated NLRP3 signaling pathway

Perfluorooctane sulfonate (PFOS) is not readily degradable in the natural environment, and PFOS is widely used in industry. Globally, PFOS exposure occurs in the environment. PFOS is persistent and non-biodegradable. The general public can come into contact with PFOS by inhaling PFOS-contaminated dust and air, drinking contaminated water, eating contaminated food. Thus, PFOS induces potential health damage globally. In this study, the effect of PFOS on aging of the liver was investigated. In an in vitro cellular model, a series of biochemical experiments were conducted via cell proliferation assays, flow cytometry, immunocytochemistry and laser confocal microscopy. It was found that PFOS led to hepatocyte senescence via Sa-β-gal staining and detection of senescence markers (p16, p21 and p53). In addition, PFOS also led to oxidative stress and inflammation. Mechanistic studies have shown that PFOS can lead to elevated mitochondrial ROS in hepatocytes through calcium overload. ROS cause alterations in mitochondrial membrane potential, subsequently inducing mPTP (mitochondrial permeability transition pore) opening, which in turn releases mt-DNA from mitochondria into the cytoplasm, thus activating NLRP3, which causes the senescence of hepatocytes. Based on this, we further analyzed the effect of PFOS on liver aging in vivo and found that PFOS caused the aging of liver tissues. On this basis, we preliminarily investigated the effect of β-carotene on the aging damage caused by PFOS and found that it could alleviate the liver aging caused by PFOS. In summary, the current study shows that PFOS causes aging damage to the liver, and this study provides a more in-depth understanding of the toxicity characteristics of PFOS. •PFOS causes liver aging, inflammation and oxidative stress.•PFOS induces hepatocytes aging and oxidative stress.•PFOS leads to liver aging through the mt-DNA-mediated NLRP3 signaling pathway.