Engineered nanoparticle respiratory exposure and potential risks for cardiovascular toxicity: Predictive tests and biomarkers
Tissue Injury Team, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. Inhalation Toxicology
(Impact Factor: 2.26).
08/2009; 21 Suppl 1(supplement 1):68-73. DOI: 10.1080/08958370902942566
The most attractive properties of engineered nanomaterials for technological applications, including their small size, large surface area, and high reactivity, are also the main factors for their potential toxicity. Based on ambient ultrafine particle research, it is predicted that nanosized particles may have deeper pulmonary deposition, higher biological activity, and a tendency for extrapulmonary translocation compared to larger particles. In this regard, nanoparticle exposure, by direct or indirect mechanisms, may lead to unexpected distant responses, involving the immune system, cardiovascular system, liver, kidney, and brain. The systemic effects may induce or modify the progression of existing diseases such as cardiovascular disease. Current experimental toxicity evaluation of engineered nanomaterials, specifically carbon nanotubes, demonstrated that deposition of these materials in the lung leads to inflammation and fibrosis. The local toxicity is associated with cardiovascular effects related to atherosclerosis. Although translocation of carbon nanotubes into the systemic circulation is hypothetically possible, there is no current evidence to support this hypothesis. However, studies pointed out that carbon nanotube-induced lung inflammation results in a release of inflammatory mediators and activation of blood cells which can contribute to cardiovascular adverse effects. Furthermore, complex protein and gene expression blood analysis can help in development of biomarkers for application in human screening of nanoparticle exposure. Future studies to evaluate the systemic effects of carbon nanotube exposure under workplace or environmental exposure paradigms should be conducted.
Available from: Quan Ma
- "In vivo studies revealed that SiNPs of low dose could elicit acute and subacute pulmonary toxicity (Kaewamatawong et al., 2006). Amorphous SiNPs of different sizes induced cardiovascular toxicity in rats after intratracheal instillation (Du et al., 2013; Simeonova and Erdely, 2009). SiNPs could also induce hepatotoxicity in rats after intranasal exposure (Parveen et al., 2012; Xie et al., 2010). "
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ABSTRACT: Growing concern has been raised over the potential adverse effects of engineered nanoparticles on human health due to their increasing use in commercial and medical applications. Silica nanoparticles (SiNPs) are one of the most widely-used nanoparticles in industry and have been formulated for cellular and non-viral gene delivery in the central nerve system. However, the potential neurotoxicity of SiNPs remains largely unclear. In this study, we investigated the cellular uptake of SiNPs in human SK-N-SH and mouse neuro2a (N2a) neuroblastoma cells treated with 10.0 μg/ml of 15-nm SiNPs for 24 h by transmission electron microcopy. We found that SiNPs were mainly localized in the cytoplasm of the treated cells. The treatment of SiNPs at various concentrations impaired the morphology of SK-N-SH and N2a cells, characterized by increased number of round cells, diminishing of dendrite-like processes and decreased cell density. SiNPs significantly decreased the cell viability, induced cellular apoptosis, and elevated the levels of intracellular reactive oxygen species (ROS) in a dose-dependent manner in both cell lines. Additionally, increased deposit of intracellular β-amyloid 1-42 (Aβ1-42) and enhanced phosphorylation of tau at Ser262 and Ser396, two specific pathological hallmarks of Alzheimer's disease (AD), were observed in both cell lines with SiNPs treatment. Concomitantly, the expression of amyloid precursor protein (APP) was up-regulated, while amyloid-β-degrading enzyme neprilysin was down-regulated in SiNP-treated cells. Finally, activity-dependent phosphorylation of glycogen syntheses kinase (GSK)-3β at Ser9 (inactive form) was significantly decreased in SiNP-treated SK-N-SH cells. Taken together, these data demonstrated that exposure to SiNPs induced neurotoxicity and pathological signs of AD. The pre-Alzheimer-like pathology induced by SiNPs might result from the dys-regulated expression of APP/neprilysin and activation of GSK-3β. This is the first study with direct evidence indicating that in addition to neurotoxicity induced by SiNPs, the application of SiNPs might increase the risk of developing AD.
- "However, in technological applications, these properties may represent factors for their potential toxicity. Epidemiological and experimental studies on ambient ultrafine particle indicate that nanosized particles may have deeper pulmonary deposition, higher biological activity and a tendency for extrapulmonary translocation compared to larger particles (Oberdörster et al., 2002; Shimida et al., 2006; Simeonova & Erdely, 2009; Zhu et al., 2009). It is speculated that inhaled nanoscaled particles may escape from phagocytosis by lung alveolar macrophages and enter into the blood circulation (Nemmar et al., 2001). "
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ABSTRACT: Abstract Histological and immunocytochemical methods were used to examine rats renal responses to intratracheal (i.t.) instillation of model cadmium-containing silica nanoparticles (Cd-SiNPs), also exploring whether these potential modifications would be associated with toxicogenomic changes. Renal effects of Cd-SiNPs (1mg/rat), CdCl2 (400µg/rat), SiNPs (600µg/rat), or 0.1 ml saline (control), assessed 7 and 30 days post-i.t., included (i) induction of apoptosis, (ii) cell proliferation, and (iii) the overall toxic response evaluated by TUNEL staining, PCNA immunohistochemistry, as well as PAS and Hematoxylin & Eosin, respectively. Area-specific apoptosis was observed in all treatment groups, the cortex and inner medulla being the most affected regions: the apoptotic changes were apparent 7 days post-exposure in both areas, and were still observable in inner medulla at day 30 (th). Apoptotic frequency increase was more pronounced in Cd-SiNP-treated animals compared to either CdCl2 or SiNPs groups. At day 7(th), the observed parallel increased number of PCNA immunopositive cells may be associated with an enhanced cell proliferation aimed at replacing the damaged cells. Histopathological findings demonstrated comparable morphological changes of the renal structure (at glomerular and tubular levels) occurring after all treatments at both time-points and more markedly 30 days after instillation. Both morphological and toxicogenomic evaluations confirmed long-lasting renal effects of Cd-SiNPs on apoptosis and regulatory processes. Bare SiNPs i.t. administration caused morphological and apoptotic changes but did not modify gene expression profile in kidney. These findings substantiate the notion that multiple assays and an integrated testing strategy should be recommended to characterize toxicological responses to nanoparticles in mammalian systems.
Available from: Vincent A. Hackley
- "It is well understood from epidemiological studies that pulmonary particulate matter (PM) exposure has been associated with adverse cardiovascular effects (Pope et al., 1995, 2002; Samet et al., 2000; Liao et al., 2011; Beckerman et al., 2012; Hsieh et al., 2010). More recently, respiratory exposure to various nanoparticles in animal models was also found to produce cardiovascular responses (Mann et al., 2012; Simeonova and Erdely, 2009), which are at times present in the absence of pulmonary measures toxicity (Nurkiewicz et al., 2008). Therefore both pulmonary and cardiovascular indices of toxicity were examined at 1 and 7 d after exposure to Ag sprays. "
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ABSTRACT: Exposure to wet aerosols generated during use of spray products containing silver (Ag) has not been evaluated. The goal was to assess the potential for cardiopulmonary toxicity following an acute inhalation of wet silver colloid. Rats were exposed by inhalation to a low concentration (100 μg/m(3) ) using an undiluted commercial antimicrobial product (20 mg/L total silver; approximately 33 nm mean aerodynamic diameter [MAD]) or to a higher concentration (1000 μg/m(3)) using a suspension (200 mg/L total silver; approximately 39 nm MAD) synthesized to possess a similar size distribution of Ag nanoparticles for 5 h. Estimated lung burdens from deposition models were 0, 1.4, or 14 μg Ag/rat after exposure to control aerosol, low, and high doses, respectively. At 1 and 7 d postexposure, the following parameters were monitored: pulmonary inflammation, lung cell toxicity, alveolar air/blood barrier damage, alveolar macrophage activity, blood cell differentials, responsiveness of tail artery to vasoconstrictor or vasodilatory agents, and heart rate and blood pressure in response to isoproterenol or norepinephrine, respectively. Changes in pulmonary or cardiovascular parameters were absent or nonsignificant at 1 or 7 d postexposure with the exceptions of increased blood monocytes 1 d after high-dose Ag exposure and decreased dilation of tail artery after stimulation, as well as elevated heart rate in response to isoproterenol 1 d after low-dose Ag exposure, possibly due to bioavailable ionic Ag in the commercial product. In summary, short-term inhalation of nano-Ag did not produce apparent marked acute toxicity in this animal model.
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