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ABSTRACT: 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.
Inhalation Toxicology 02/2011; 23(2):95-103. · 1.92 Impact Factor
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ABSTRACT: Because associations have been reported between inhaled ambient ultrafine particles and increased risk of cardiopulmonary disease, it has been suggested that inhaled engineered nanoparticles (NPs) may also induce adverse effects on the cardiovascular system.
We examined the long-term cardiovascular effects of inhaled nickel hydroxide NPs (nano-NH) using a sensitive mouse model.
Hyperlipidemic, apoprotein E-deficient (ApoE-/-) mice were exposed to nano-NH at either 0 or 79 μg Ni/m3, via a whole-body inhalation system, for 5 hr/day, 5 days/week, for either 1 week or 5 months. We measured various indicators of oxidative stress and inflammation in the lung and cardiovascular tissue, and we determined plaque formation on the ascending aorta.
Inhaled nano-NH induced significant oxidative stress and inflammation in the pulmonary and extrapulmonary organs, indicated by up-regulated mRNA levels of certain antioxidant enzyme and inflammatory cytokine genes; increased mitochondrial DNA damage in the aorta; significant signs of inflammation in bronchoalveolar lavage fluid; changes in lung histopathology; and induction of acute-phase response. In addition, after 5-month exposures, nano-NH exacerbated the progression of atherosclerosis in ApoE-/- mice.
This is the first study to report long-term cardiovascular toxicity of an inhaled nanomaterial. Our results clearly demonstrate that long-term exposure to inhaled nano-NH can induce oxidative stress and inflammation, not only in the lung but also in the cardiovascular system, and that this stress and inflammation can ultimately contribute to progression of atherosclerosis in ApoE-/- mice.
Environmental Health Perspectives 02/2011; 119(2):176-81. · 7.04 Impact Factor
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ABSTRACT: The purpose of this exploratory study within the integrated subchronic inhalation exposure study (Lippmann et al., 2005) was to identify genes in heart and lung tissue that changed in expression level as a result of subchronic exposure to concentrated ambient particles (CAPs). Identification of CAPs exposure-related changes in gene expression could serve in the formulation of mechanistic hypotheses and/or to suggest possible biomarkers of exposure. In this exploratory study undertaken here, tissues from multiple replicates of ApoE/low-density-lipoprotein double knockout (DK) mice were examined for relative exposure-related changes in gene expression. Due to limited resources, the number of replicates was three for each tissue (lung and heart) of each exposure condition (CAPs or air control). A rigorous comparison of exposure versus control data using the "significance analysis of microarrays" (SAM) method indicated that only one gene was differentially expressed at a significant level. However, when using a less restrictive, nonstatistical analytical treatment of the data, several genes that might be involved in PM-related heart or lung pathology, and/or the circadian rhythm of physiological processes, were identified. A more comprehensive study is required to mre definitively assess differences in gene expression in heart and lung resulting from exposure to CAPs.
Inhalation Toxicology 05/2005; 17(4-5):225-33. · 1.92 Impact Factor
