Double-Sided Nano-ZnO: Superior Antibacterial Properties and Induced Hepatotoxicity in Zebrafish Embryos.

Zinc oxide nanoparticles (Nano-ZnO) have been widely used in the food, cosmetics, and biomedical fields due to their excellent antibacterial and antioxidant properties. However, with the widespread application of Nano-ZnO, Nano-ZnO inevitably enters the environment and living organisms, causing harm to human health and ecosystem safety. Therefore, the biosafety and toxicological issues of Nano-ZnO are gradually being emphasized. Our study found that Nano-ZnO has superior antibacterial properties compared to ofloxacin in the fight against Staphylococcus aureus ( S. aureus ). Given that ofloxacin can inhibit bacterial-induced inflammation, we constructed a model of bacterial inflammation using S. aureus in zebrafish. We found that Nano-ZnO inhibited the NF-κB-mediated inflammatory signaling pathway. However, in the process, we found that Nano-ZnO caused hepatic steatosis in zebrafish. This suggested that Nano-ZnO had a certain hepatotoxicity, but did not affect liver development. Subsequently, we investigated the mechanism of hepatotoxicity produced by Nano-ZnO. Nano-ZnO triggered oxidative stress in the liver by generating ROS, which then induced endoplasmic reticulum stress to occur. It further activated srebp and its downstream genes fasn and acc1 , which promoted the accumulation of fatty acid synthesis and the development of steatosis, leading to the development of nonalcoholic fatty liver disease (NAFLD). To address the hepatotoxicity of Nano-ZnO, we added carbon dots for the treatment of NAFLD. The carbon dots were found to normalize the steatotic liver. This provided a new strategy to address the hepatotoxicity caused by Nano-ZnO. In this work, we systematically analyzed the antibacterial advantages of Nano-ZnO in vivo and in vitro, explored the mechanism of Nano-ZnO hepatotoxicity, and proposed a new method to treat Nano-ZnO hepatotoxicity.