S4: Toxicity of zinc oxide nanoparticles
Toxicity of zinc oxide nanoparticles: from animals to mode of action
National Health Research Institutes, Taiwan
Associate Director and Investigator
Metal-based nanoparticles have great application in industries. However, Nanoparticles frequently have remarkably physicochemical properties which will modulate their disposition and toxic potential in biological systems. Among metal oxide nanoparticles, zinc oxide nanoparticle (ZnONP) is one of the most potent inducers for pulmonary inflammation. We performed a series of experiments to characterize the hazard of ZnONP. Comparing the kinetics and tissue distribution of 10 nm, 71 nm ZnONP and zinc ion via a single dose of intravenous injection in mice, we found that majority of ZnONPs were eliminated within 28 days and the smaller ZnONP tended to accumulate preferentially in some organs. A physiology-based pharmacokinetic models was developed for ZnONPs. While inhalation of ZnONP and zinc ion both caused acute pulmonary inflammation, only inhalation of ZnONP resulted in the systemic adverse effects in mice. It appears that the particulate characters of ZnONP might contribute to the systemic adverse effects. More recently, we demonstrated a mode of action for ZnONP-induced acute pulmonary inflammation in mice. ZnONP increased proinflammatory cytokines, accompanied with an increased expression of aryl hydrocarbon receptor (AhR) and its downstream target cytochrome P450 1A1 (CYP1A1) in macrophages in vitro and in mouse lung epithelia in vivo. The involvement of AhR pathway in ZnONP-induced inflammation was further demonstrated by co-treatment with AhR inhibitors in vitro and AhR knockout in vivo. These information allows us to better understand the hazard of ZnONP.