Zinc oxide (ZnO) particles induce acute occupational inhalation illness in humans and rats. However, the molecular mechanisms of ZnO particles on the respiratory system remain unclear. The global metabolic responses of nano- and fine-sized ZnO particles in a rat inhalation model were examined by researchers at National Taiwan University (NTU). The possible molecular mechanisms of ZnO particles in the respiratory system are suggested by Dr. Tsun-Jen Cheng and Ching-Yu Lin groups. Metabolic effects of ZnO particles are associated with cell anti-oxidation, energy metabolism, DNA damage, and membrane stability in the rat lung. “A metabolic approach provides more thorough molecular events of ZnO particles” said by Dr. Lin. This study has been published online in Nanotoxicology in March, 2016.
This study was conducted by Dr. Tsun-Jen Cheng, a professor in Inst. Occupational Medicine and Industrial Hygiene, Dr. Ching-Yu Lin, an associated professor in Inst. Environmental Health in College of Public Health at NTU, and Mr. Sheng-Han Lee, a doctoral student in Inst. Environmental Health at NTU.
This study assessed global metabolic responses of the respiratory system of rats inhaled ZnO particles by a nuclear magnetic resonance (NMR)-based metabolomic approach. Male Sprague-Dawley rats were treated with a series of doses of nano-sized (35 nm) or fine-sized (250 nm) ZnO particles. After 24 hours, bronchoalveolar lavage fluid (BALF) and lung tissues were taken for NMR instrumental analysis, followed by multivariate statistical analysis, such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA).
The results of PCA and PLSDA models from the analysis of BALF and lung NMR spectra demonstrated that dose response trends were restricted to the 250nm ZnO particle exposure group and were not observed in the 35nm ZnO particle exposure group. Among detected metabolites, changes of isoleucine, valine, acetate, trimethylamine n-oxide, taurine, glycine, formate, ascorbate, glycerophosphocholine, taurine, glucose, phosphorylcholine-containing lipids, and fatty acyl chains reflects the perturbation of ZnO particle exposure in the respiratory system, especially when exposed to find-sized ZnO particles. These metabolic changes are associated with cell anti-oxidation, energy metabolism, DNA damage, and membrane stability. The results of this study suggest the plausible molecular mechanisms involving in toxicity of ZnO particle. “Future studies to verify the mechanisms of ZnO-induced toxicity and develop biomarkers will further the knowledge for ZnO-risk assessment” said by Dr. Lin.