Journal of Molecular Histology

, Volume 47, Issue 3, pp 273–286 | Cite as

In vitro and in vivo evaluation of the toxicities induced by metallic nickel nano and fine particles

  • Ruth Magaye
  • Yuanliang Gu
  • Yafei Wang
  • Hong Su
  • Qi Zhou
  • Guochuan Mao
  • Hongbo Shi
  • Xia Yue
  • Baobo Zou
  • Jin Xu
  • Jinshun ZhaoEmail author
Original Paper


Nickel nanoparticles (Ni NPs) have been applied in various fields along with the rapid development of nanotechnology. However, the potential adverse health effects of the Ni NPs are unclear. To investigate the cyto- and genotoxicity and compare the differences between the Ni NPs and the nickel fine particles (Ni FPs), Sprague-Dawley (SD) rats and A549 cells were treated with different doses of Ni NPs or FPs. Intra-tracheal instillation of Ni NPs and FPs caused acute toxicity in the lungs, liver and kidneys of the SD rats. Even though the histology of the lungs showed hyperplastic changes and the protein expression of HO-1 and Nrf2 detected by western blot showed lung burden overload, no significant increase was observed to the expression level of oncoprotein C-myc. The results from cell titer-Glo assay and comet assay indicated that Ni NPs were more potent in causing cell toxicity and genotoxicity in vitro than Ni FPs. In addition, Ni NPs increased the expression of C-myc in vitro, but these increases may not have been due to oxidative stress since no significant dose-dependent changes were seen in HO-1 and Nrf2 expressions. Although Ni NPs have the potential to cause DNA damage in A549 cells in vitro, the molecular mechanisms that led to these changes and their tumorigenic potential is still debatable. In short, Ni NPs were more potent in causing cell toxicity and genotoxicity in vitro than Ni FPs, and intra-tracheal instillation of Ni NPs and FPs caused toxicity in organs of the SD rats, while it showed similar to the effects for both particle types. These results suggested that both Ni NPs and FPs have the potential to be harmful to human health, and Ni NPs may have higher cyto- and genotoxic effects than Ni FPs under the same treatment dose.


Nickel Nanoparticles Fine particles Cytotoxicity Genotoxicity Carcinogenicity 


Ni FPs

Nickel fine particles

Ni NPs

Nickel nanoparticles

SD rat

Sprague dawley rat


International Agency for Research in Cancer


Scanning electron microscopy


Total protein


Alkaline phosphatase


Aspartate transaminase


Alanine aminotransferase

Total B

Total bilirubin

Direct B

Conjugated bilirubin


Blood urea nitrogen


Creatine kinase


Creatine kinase isoenzymes


High-density lipoproteincholesterol


Whole blood count


Neutrophil %


Lymphocyte %


Monocyte %


Eosinophil %


Red blood cells




Mean corpuscular hemoglobin concentration




Chronic kidney disease


Coronary artery disease



The contribution of Mrs. Linda Bowman in the preparation of this article is greatly appreciated. The authors also thank all institutions for supporting this research. In addition, the author gratefully acknowledges the support of K.C. Wong Education Foundation, Hong Kong.


This work was partly supported by the National Nature Science Foundation of China (No. 81273111), the Ningbo Scientific Project (No. 2012C5019), the Science Technology Department of Zhejiang Province (Nos. 2015C33148 and 2015C37117) and the Scientific Innovation Team Project of Ningbo (No. 2011B82014).

Authors’ contributions

J.Z. led all participators to design this study, was responsible for coordinating the study and drafted the manuscript. R.M., Y.W. and B.Z. conducted the animal experiments. Y.G., H.S. and Q.Z. conducted the in vitro experiments and processed the toxicological data. G.M., X.Y., H.S. and J.X. performed the data collection, interpretation and statistical analysis. R.M. and Y.G. contributed to the preparation of the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interests

The authors declare that they have no competing interests.

Ethics approval

The in vivo study had been examined and approved by Ningbo University Experimental Animal Ethics Committee. There was no violation of experimental animal ethics principle in this study.


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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological TechnologyMedicine School of Ningbo UniversityNingboChina

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