Pulmonary response after exposure to inhaled nickel hydroxide nanoparticles: Short and long-term studies in mice

Abstract

Short and long-term pulmonary response to inhaled nickel hydroxide nanoparticles (nano-Ni(OH)_2, CMD = 40 nm) in C57BL/6 mice was assessed using a whole body exposure system. For short-term studies mice were exposed for 4 h to nominal concentrations of 100, 500, and 1000 μg/m³. For long-term studies mice were exposed for 5 h/d, 5 d/w, for up to 5 months (m) to a nominal concentration of 100 μg/m³. Particle morphology, size distribution, chemical composition, solubility, and intrinsic oxidative capacity were determined. Markers of lung injury and inflammation in bronchoalveolar lavage fluid (BALF); histopathology; and lung tissue elemental nickel content and mRNA changes in macrophage inflammatory protein-2 (Mip-2), chemokine ligand 2 (Ccl2), interleukin 1-alpha (Il-1α), and tumor necrosis factor-alpha (Tnf-α) were assessed. Dose-related changes in BALF analyses were observed 24 h after short-term studies while significant changes were noted after 3 m and/or 5 m of exposure (24 h). Nickel content was detected in lung tissue, Ccl2 was most pronouncedly expressed, and histological changes were noted after 5 m of exposure. Collectively, data illustrates nano-Ni(OH)₂ can induce inflammatory responses in C57BL/6 mice.

Keywords::

• Nickel
• nanoparticles
• inhalation
• lung
• pulmonary response

Acknowledgments

The authors would like to thank Mr Mianhua Zhong for assistance in setting up the exposure system; Mr Alan Bowers for analyzing tissue samples with the GFAAS; and Dr Alice Liang and Mr Eric W. Roth from NYU School of Medicine Image Core Facility for assistance with TEM analyses. In addition, the authors graciously thank Ms Deborah Andrews, Ms Mette Schladweiler, and Dr Urmila Kodavanti of the U.S. Environmental Protection Agency for performing NAG and MCP-1 analyses.

Declaration of Interest: This research was supported by the National Institutes of Health (RO1 ES015439 to L.C.; RO1 CA134218 to A.E.; P30 ESO1247, and ESO0260); and the Environmental Protection Agency (STAR Grant RD-8325280 to T.G.). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.