Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity in male Sprague-Dawley rats

Nalabotu, Siva K.; Kolli, Madhukar B.; Triest, William E.; Jane, Y. C.; Manne, Nandini D.P.K.; Katta, Anjaiah; Addagarla, Hari S.; Rice, Kevin M.; Blough, Eric R.

doi:10.2147/ijn.s25119

Cited by 117 publications

(88 citation statements)

References 29 publications

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“…[24][25][26] In contrast, other in vitro and in vivo experiments suggest that CeO 2 nanoparticles produce inflammation, reactive oxygen species, lipid peroxidation, liver and lung damage, acute and chronic fibrotic effects, and altered macrophage phenotypes. [27][28][29][30][31] Variation in target species/ cell type, experimental design (exposure concentration and duration) and nanoparticle characteristics (shape, size, purity, Figure 1, stained with propidium iodide and analyzed using flow cytometry. Notes: Data are presented as the mean ± standard error of the mean and analyzed by analysis of variance, followed by Tukey's post hoc test.…”

Section: Discussionmentioning

confidence: 99%

Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes

Hussain¹,

Al-Nsour²,

Rice³

et al. 2012

IJN

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Background: Cerium dioxide (CeO 2 ) nanoparticles have potential therapeutic applications and are widely used for industrial purposes. However, the effects of these nanoparticles on primary human cells are largely unknown. The ability of nanoparticles to exacerbate pre-existing inflammatory disorders is not well documented for engineered nanoparticles, and is certainly lacking for CeO 2 nanoparticles. We investigated the inflammation-modulating effects of CeO 2 nanoparticles at noncytotoxic concentrations in human peripheral blood monocytes. Methods: CD14+ cells were isolated from peripheral blood samples of human volunteers. Cells were exposed to either 0.5 or 1 µg/mL of CeO 2 nanoparticles over a period of 24 or 48 hours with or without lipopolysaccharide (10 ng/mL) prestimulation. Modulation of the inflammatory response was studied by measuring secreted tumor necrosis factor-alpha, interleukin-1beta, macrophage chemotactic protein-1, interferon-gamma, and interferon gamma-induced protein 10. Results: CeO 2 nanoparticle suspensions were thoroughly characterized using dynamic light scattering analysis (194 nm hydrodynamic diameter), zeta potential analysis (−14 mV), and transmission electron microscopy (irregular-shaped particles). Transmission electron microscopy of CD14 + cells exposed to CeO 2 nanoparticles revealed that these nanoparticles were efficiently internalized by monocytes and were found either in vesicles or free in the cytoplasm. However, no significant differences in secreted cytokine profiles were observed between CeO 2 nanoparticletreated cells and control cells at noncytotoxic doses. No significant effects of CeO 2 nanoparticle exposure subsequent to lipopolysaccharide priming was observed on cytokine secretion. Moreover, no significant difference in lipopolysaccharide-induced cytokine production was observed after exposure to CeO 2 nanoparticles followed by lipopolysaccharide exposure. Conclusion: CeO 2 nanoparticles at noncytotoxic concentrations neither modulate pre-existing inflammation nor prime for subsequent exposure to lipopolysaccharides in human monocytes from healthy subjects.

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Section: Discussionmentioning

confidence: 99%

Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes

Hussain¹,

Al-Nsour²,

Rice³

et al. 2012

IJN

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“…route resulted in the accumulation of NMs in the liver, elevations in serum alanine transaminase levels and a reduction in albumin levels (Nalabotu et al, 2012). The authors also showed that the animals exposed to the NMs had a reduced overall liver weight, enlarged hepatocytes, sinusoidal dilatations and an accumulation of granular materials.…”

Section: Intratracheal Instillation (It) Routementioning

confidence: 92%

Toxicological effect of engineered nanomaterials on the liver

Kermanizadeh

Gaiser

Johnston

et al. 2014

British J Pharmacology

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The liver has a crucial role in metabolic homeostasis, as it is responsible for the storage, synthesis, metabolism and redistribution of carbohydrates, fats and vitamins, and numerous essential proteins. It is also the principal detoxification centre of the body, removing xenobiotics and waste products by metabolism or biliary excretion. An increasing number of studies have shown that some nanomaterials (NMs) are capable of distributing from the site of exposure (e.g. lungs, gut) to a number of secondary organs, including the liver. As a secondary exposure site the liver has been shown to preferentially accumulate NMs (>90% of translocated NMs compared with other organs), and alongside the kidneys may be responsible for the clearance of NMs from the blood. Research into the toxicity posed by NMs to the liver is expanding due to the realization that NMs accumulate in this organ following exposure via a variety of routes (e.g. ingestion, injection and inhalation). Thus it is critical to consider what advances have been made in the investigation of NM hepatotoxicity, as well as appraising the quality of the information available and gaps in the knowledge that still exist. The overall aim of this review is to outline what data are available in the literature for the toxicity elicited by NMs to the liver in order to establish a weight of evidence approach (for risk assessors) to inform on the potential hazards posed by NMs to the liver. LINKED ARTICLESThis article is part of a themed section on Nanomedicine. To view the other articles in this section visit http://dx

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“…nanomaterial clearance from blood and sequestration and is the only organ that showed signs of injury (Nalabotu et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Persistent Hepatic Structural Alterations Following Nanoceria Vascular Infusion in the Rat

Tseng

Lor

et al. 2013

Toxicol Pathol

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Understanding the long-term effects and possible toxicity of nanoceria, a widely utilized commercial metal oxide, is of particular importance as it is poised for development as a therapeutic agent based on its autocatalytic redox behavior. We show here evidence of acute and subacute adverse hepatic responses, after a single infusion of an aqueous dispersion of 85 mg/kg, 30 nm nanoceria into Sprague Dawley rats. Light and electron microscopic evidence of avid uptake of nanoceria by Kupffer cells was detected as early as 1 hr after infusion. Biopersistent nanoceria stimulated cluster of differentiation 3 þ lymphocyte proliferation that intermingled with nanoceria-containing Kupffer cells to form granulomata that were observed between days 30 and 90. Ultrastructural tracking of ceria nanoparticles revealed aggregated nanoceria in phagolysosomes. An increased formation of small nanoceria over time observed in the latter suggests possible dissolution and precipitation of nanoceria. However, the pathway for nanoceria metabolism/secretion remains unclear. Although frank hepatic necrosis was not observed, the retention of nanoceria increased hepatic apoptosis acutely, this persisted to day 90. These findings, together with our earlier reports of 5-nm ceria-induced liver toxicity, provide additional guidance for nanoceria development as a therapeutic agent and for its risk assessment.

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Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity in male Sprague-Dawley rats

Cited by 117 publications

References 29 publications

Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes

Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes

Toxicological effect of engineered nanomaterials on the liver

Persistent Hepatic Structural Alterations Following Nanoceria Vascular Infusion in the Rat

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