Zinc Oxide Nanoparticle Caused Plasma Metabolomic Perturbations Correlate with Hepatic Steatosis.

Weidong Zhang,Jing Liu,Tianhong Shi,Wei Shen,Fuwei Li,Hongfu Zhang,Dongxue Ma,Lan Li,Yanni Feng,Shuai Yu,Fuli Li,Lingjiang Min,Yong Zhao

doi:10.3389/fphar.2018.00057

Abstract

Zinc oxide nanoparticles (ZnO NPs), known for their chemical stability and strong adsorption, are used in everyday items such as cosmetics, sunscreens, and prophylactic drugs. However, they have also been found to adversely affect organisms; previously we found that ZnO NPs disrupt pubertal ovarian development, inhibit embryonic development by upsetting γ-H2AX and NF-κB pathways, and even disturb skin stem cells. Non-targeted metabolomic analysis of biological organisms has been suggested as an unbiased tool for the investigation of perturbations in response to NPs and their underlying mechanisms. Although metabolomics has been used in nanotoxicological studies, very few reports have used it to investigate the effects of ZnO NPs exposure. In the current investigation, through a metabolomics-based approach, we discovered that ZnO NPs caused changes in plasma metabolites involved in anti-oxidative mechanisms, energy metabolism, and lipid metabolism in hen livers. These results are in line with earlier findings that ZnO NPs perturb the tricarboxylic acid cycle and in turn result in the use of alternative energy sources. We also found that ZnO NPs disturbed lipid metabolism in the liver and consequently impacted blood lipid balance. Changes in plasma metabolomes were correlated with hepatic steatosis.

Highlights

Metabolomics is considered a useful tool for environmental risk assessment (Ryan and Robards, 2006; Taylor et al, 2010)
The ultra-structure of Zinc oxide nanoparticles (ZnO NPs) used in this investigation has been published in our previous articles (Supplementary Figure S1) (Zhao et al, 2016a,b; Ge et al, 2017; Liu et al, 2017)
We found that pubertal hen’s ovarian development was perturbed (Liu et al, 2016), chicken embryonic development was inhibited (Liu et al, 2017), and even skin stem cells were disturbed by 30 nm Zinc oxide (ZnO) NPs (Ge et al, 2017)

Summary

Introduction

Metabolomics is considered a useful tool for environmental risk assessment (Ryan and Robards, 2006; Taylor et al, 2010). Non-targeted metabolomic analysis of biological organisms has been suggested as an unbiased tool for the investigation of perturbations in response to environmental toxicants and underlying mechanisms (Bundy et al, 2009; Garcia-Contreras et al, 2015; Gioria et al, 2016). Yan et al (2012) used this tool to reveal nephrotoxicity in rats after a 14-consecutive day oral administration of 50 nm ZnO NPs. Lee et al (2016) identified respiratory toxicology after ZnO NP inhalation. Lee et al (2016) identified respiratory toxicology after ZnO NP inhalation Even though these two studies investigated metabolome change after ZnO NP administration, the treatment time was relatively short (1–14 days) and they only studied metabolomic alterations in the kidneys, lungs, and bronchoalveolar lavage fluid (BALF). Systemic metabolome perturbation in animal blood has not yet been studied

Objectives

Methods

Results

Discussion

Conclusion