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

Abstract

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.

ZnO size and shape effect on antibacterial activity and cytotoxicity profile

“…Like other metal oxides, zinc oxide can change its physicochemical characteristics under the influence of the environment, and, unfortunately depending on its concentration, ZnO can be hazardous to the life of living organisms and ecosystem safety. Therefore, special attention is paid to the control of the release of toxic zinc ions from the solution, especially in vivo studies 25 , 26 . Lee et al 27 showed that the toxicity of ZnO NPs can be correlated well with the zinc concentration and through transformation thought interaction ZnO with sulphur, phosphate, and ferric oxide.…”

Dunaliella salina Microalga Restores the Metabolic Equilibrium and Ameliorates the Hepatic Inflammatory Response Induced by Zinc Oxide Nanoparticles (ZnO-NPs) in Male Zebrafish

“…Furthermore, ZnO-NPs were reported to damage the hepatic tissue as evidenced by elevated liver enzyme markers in the serum of Oreochromis niloticus and C. carpio [ 20 , 21 , 24 ] and decreased serum albumin and total protein [ 21 ]. The induced structural changes in the liver of ZnO-NPs-exposed fishes could be attributed to hepatic oxidative damage with an increased rate of lipid peroxidation and suppression of antioxidant enzymes [ 11 , 33 ].…”

“…Furthermore, it increased the triglyceride contents and the activity of the lipogenic enzymes besides the upregulation of the lipogenic genes including 6pgd , fas , and srebp1 , and the downregulation of small heterodimer partner ( shp ) and farnesoid X receptor ( fxr ). In addition, He et al recorded hepatic steatosis in ZnONPs-treated zebrafish [ 11 ]. Collectively, this could result from the promotion of fatty acid synthesis via activation of the srebp gene and its downstream genes fasn and acc1 .…”

“…Other previous studies declared that ZnO-NPs inhibit the hatchability, and normal growth, and induce morphological malformations and neurodevelopmental abnormalities in the zebrafish embryos [ 11 , 12 ] along with hematotoxicity [ 13 ], nephrotoxicity [ 14 ], reproductive toxicity [ 15 ], and immunomodulation [ 16 ] in the adult fishes. In fact, the liver is a key metabolic organ responsible for many vital functions including energy metabolism and detoxification of various environmental pollutants [ 17 , 18 , 19 ].…”

Nanoparticles in ocular applications and their potential toxicity

“…Zinc oxide NPs (ZnO-NPs) are widely used in the biomedical field and have been extensively applied for antibacterial (Singh, Sharma et al, 2021). It was found that the antibacterial activity of ZnO-NPs against Escherichia coli and Staphylococcus aureus was similar to that of levofloxacin, a commonly used broadspectrum antibiotic (He, Li et al, 2022). ZnO-NPs are considerable antibacterial agents for contact lenses to reduce the risk of infection from wear (Shayani Rad, Sabeti et al, 2020).…”