Combined exposure of nano‐titanium dioxide and polystyrene nanoplastics exacerbate oxidative stress‐induced liver injury in mice by regulating the Keap‐1/Nrf2/ARE pathway.

It is well known that polystyrene nanoplastics (PS‐NaP) and nano‐titanium dioxide (TiO2 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 TiO2 NPs in the hepatic system have not been revealed. Thus, we conducted experiments on C57BL/6 mice exposed to PS‐NaP or/and TiO2 NPs for 4 weeks. The findings suggested that PS‐NaP and TiO2 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 TiO2 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 TiO2 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. [ABSTRACT FROM AUTHOR]