Combined exposure of nano‐titanium dioxide and polystyrene nanoplastics exacerbate oxidative stress‐induced liver injury in mice by regulating the <i>Keap‐1</i> / <i>Nrf2</i> / <i>ARE</i> pathway
Tiantian Jia, Penghui Nie, Hengyi Xu
Abstract
Abstract It is well known that polystyrene nanoplastics (PS‐NaP) and nano‐titanium dioxide (TiO 2 NPs) are frequently co‐appeared in daily life and can cause liver injury when they accumulate in the liver. Nonetheless, the combined toxicological impacts and potential molecular mechanisms of PS‐NaP and TiO 2 NPs in the hepatic system have not been revealed. Thus, we conducted experiments on C57BL/6 mice exposed to PS‐NaP or/and TiO 2 NPs for 4 weeks. The findings suggested that PS‐NaP and TiO 2 NPs co‐exposed significantly altered the hepatic function parameters, levels of antioxidant‐related enzymes and genes expression of Keap‐1/Nrf2/ARE signaling pathway, as well as significantly increased the hepatic Ti contents, aggravated hepatic pathological and oxidative stress (OS) damage compared with individual exposure to PS‐NaP or TiO 2 NPs. Using N‐Acetyl‐L‐cysteine (NAC), an OS inhibitor, we further demonstrated that OS played a pivotal role in coexposure‐induced liver injury. NAC reduced the levels of OS in mice, which mitigated co‐exposure‐induced liver injury. Taken together, we proposed that PS‐NaP and TiO 2 NPs co‐exposed activated the Keap‐1 , then inhibited the recognition of Nrf2 and ARE , consequently exacerbated liver injury. These findings shed light on the co‐toxicity and potential mechanism of nanoplastics and nanoparticles, which informed the risk assessment of human exposure to environmental pollutants.