Comparative pulmonary toxicity of inhaled nickel nanoparticles; role of deposited dose and solubility.
In this pilot study, we investigated which physicochemical properties of nickel hydroxide nanoparticles (nano-NH) were mainly responsible in inducing pulmonary toxicity. First, we studied the role of nickel ions solubilized from nano-NH by comparing the toxic effects of nano-NH to those of readily soluble nickel sulfate nanoparticles (nano-NS). Additionally, to test whether there was a non-specific stress response due to particle morphology, we compared the toxicity of nano-NH with that of carbon nanoparticles (nano-C) and titanium dioxide nanoparticles (nano-Ti), both of which had similar physical properties such as particle size and shape, to nano-NH. We exposed mice to each type of nanoparticles for 4?h via a whole-body inhalation system and examined oxidative stress and inflammatory responses in the lung. We also determined the lung burden and clearance of Ni following nano-NH and nano-NS exposures. The results showed that lung deposition of nano-NH was significantly greater than that of nano-NS and nano-NH appeared to have stronger inflammogenic potential than nano-NS even when lung Ni burden taken into consideration. This suggests that the toxicity of nano-NH is not driven solely by released Ni ions from deposited nano-NH particles. However, it is unlikely that the greater toxic potential of nano-NH is attributable to a generic stress response from any nanoparticle exposure, since nano-C and nano-Ti did not elicit toxic responses similar to those of nano-NH. These results indicate that the observed pulmonary toxicity by inhaled nano-NH were chemical-specific and deposited dose and solubility are key factors to understand toxicity induced by nano-NH.
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.
Gi Soo
GS
Kang
Patricia A
PA
Gillespie
Albert
A
Gunnison
Hernan
H
Rengifo
Jeffrey
J
Koberstein
Lung-Chi
LC
Chen
D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006878:Hydroxides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D008168:Lung / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D009532:Nickel / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D010865:Pilot Projects; D012333:RNA, Messenger / Q000378:metabolism; D012995:Solubility; D014018:Tissue Distribution
D015415:Biomarkers; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D006878:Hydroxides; D008565:Membrane Proteins; D012333:RNA, Messenger; C037473:nickel hydroxide; C029938:nickel sulfate; D009532:Nickel; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse