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Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats.

ABSTRACT: Titanium dioxide (TiO?) and carbon black (CB) nanoparticles (NPs) have biological effects that could aggravate pulmonary emphysema. The aim of this study was to evaluate whether pulmonary administration of TiO? or CB NPs in rats could induce and/or aggravate elastase-induced emphysema, and to investigate the underlying molecular mechanisms.On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg?¹ pancreatic porcine elastase or saline. On day 7, they received an intratracheal instillation of TiO? or CB (at 100 and 500??g) dispersed in bovine serum albumin or bovine serum albumin alone. Animals were sacrificed at days 8 or 21, and bronchoalveolar lavage (BAL) cellularity, histological analysis of inflammation and emphysema, and lung mRNA expression of heme oxygenase-1 (HO-1), interleukin-1? (IL-1?), macrophage inflammatory protein-2, monocyte chemotactic protein-1, and matrix metalloprotease (MMP)-1, and -12 were measured. In addition, pulmonary MMP-12 expression was also analyzed at the protein level by immunohistochemistry.TiO? NPs per se did not modify the parameters investigated, but CB NPs increased perivascular/peribronchial infiltration, and macrophage MMP-12 expression, without inducing emphysema. Elastase administration increased BAL cellularity, histological inflammation, HO-1, IL-1? and macrophage MMP-12 expression and induced emphysema. Exposure to TiO? NPs did not modify pulmonary responses to elastase, but exposure to CB NPs aggravated elastase-induced histological inflammation without aggravating emphysema.TiO? and CB NPs did not aggravate elastase-induced emphysema. However, CB NPs induced histological inflammation and MMP-12 mRNA and protein expression in macrophages.

SUBMITTER: Roulet A

PROVIDER: S-EPMC3499434 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats.

Roulet Agnès A Armand Lucie L Dagouassat Maylis M Rogerieux Françoise F Simon-Deckers Angélique A Belade Esther E Van Nhieu Jeanne Tran JT Lanone Sophie S Pairon Jean-Claude JC Lacroix Ghislaine G Boczkowski Jorge J

BMC pulmonary medicine 20120731

<h4>Background</h4>Titanium dioxide (TiO₂) and carbon black (CB) nanoparticles (NPs) have biological effects that could aggravate pulmonary emphysema. The aim of this study was to evaluate whether pulmonary administration of TiO₂ or CB NPs in rats could induce and/or aggravate elastase-induced emphysema, and to investigate the underlying molecular mechanisms.<h4>Methods</h4>On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg⁻¹ pancreatic porcine elastase or saline. On day 7 ...[more]

PMID: 22849372

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Project description:The toxicokinetics of nanomaterials are an important factor in toxicity, which may be affected by slow clearance and/or distribution in the body.Four types of nickel oxide (NiO) nanoparticles were single-administered intratracheally to male F344 rats at three doses of 0.67-6.0 mg/kg body weight. The rats were sacrificed under anesthesia and the lung, thoracic lymph nodes, bronchoalveolar lavage fluid, liver, and other organs were sampled for Ni burden measurement 3, 28, and 91 days post-administration; Ni excretion was measured 6 and 24 h after administration. Solubility of NiO nanoparticles was determined using artificial lysosomal fluid, artificial interstitial fluid, hydrogen peroxide solution, pure water, and saline. In addition, macrophage migration to trachea and phagosome-lysosome-fusion rate constants were estimated using pulmonary clearance and dissolution rate constants.The wire-like NiO nanoparticles were 100% dissolved by 24 h when mixed with artificial lysosomal fluid (dissolution rate coefficient: 0.18/h); spherical NiO nanoparticles were 12% and 35% dissolved after 216 h when mixed with artificial lysosomal fluid (1.4?×?10-3 and 4.9?×?10-3/h). The largest irregular-shaped NiO nanoparticles hardly dissolved in any solution, including artificial lysosomal fluid (7.8?×?10-5/h). Pulmonary clearance rate constants, estimated using a one-compartment model, were much higher for the NiO nanoparticles with a wire-shape (0.069-0.078/day) than for the spherical and irregular-shaped NiO nanoparticles (0-0.012/day). Pulmonary clearance rate constants of the largest irregular-shaped NiO nanoparticles showed an inverse correlation with dose. Translocation of NiO from the lungs to the thoracic lymph nodes increased in a time- and dose-dependent manner for three spherical and irregular-shaped NiO nanoparticles, but not for the wire-like NiO nanoparticles. Thirty-five percent of the wire-like NiO nanoparticles were excreted in the first 24 h after administration; excretion was 0.33-3.6% in that time frame for the spherical and irregular-shaped NiO nanoparticles.These findings suggest that nanomaterial solubility differences can result in variations in their pulmonary clearance. Nanoparticles with moderate lysosomal solubility may induce persistent pulmonary inflammation.

Project description:BackgroundEpidemiological emerging evidence shows that human exposure to some nanosized materials present in the environment would contribute to the onset and/or progression of Alzheimer's disease (AD). The cellular and molecular mechanisms whereby nanoparticles would exert some adverse effects towards neurons and take part in AD pathology are nevertheless unknown.ResultsHere, we provide the prime evidence that titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) bind the cellular form of the prion protein (PrPC), a plasma membrane protein well known for its implication in prion diseases and prion-like diseases, such as AD. The interaction between TiO2- or CB-NPs and PrPC at the surface of neuronal cells grown in culture corrupts PrPC signaling function. This triggers PrPC-dependent activation of NADPH oxidase and subsequent production of reactive oxygen species (ROS) that alters redox equilibrium. Through PrPC interaction, NPs also promote the activation of 3-phosphoinositide-dependent kinase 1 (PDK1), which in turn provokes the internalization of the neuroprotective TACE α-secretase. This diverts TACE cleavage activity away from (i) TNFα receptors (TNFR), whose accumulation at the plasma membrane augments the vulnerability of NP-exposed neuronal cells to TNFα -associated inflammation, and (ii) the amyloid precursor protein APP, leading to overproduction of neurotoxic amyloid Aβ40/42 peptides. The silencing of PrPC or the pharmacological inhibition of PDK1 protects neuronal cells from TiO2- and CB-NPs effects regarding ROS production, TNFα hypersensitivity, and Aβ rise. Finally, we show that dysregulation of the PrPC-PDK1-TACE pathway likely occurs in the brain of mice injected with TiO2-NPs by the intra-cerebro-ventricular route as we monitor a rise of TNFR at the cell surface of several groups of neurons located in distinct brain areas.ConclusionOur in vitro and in vivo study thus posits for the first time normal cellular prion protein PrPC as being a neuronal receptor of TiO2- and CB-NPs and identifies PrPC-coupled signaling pathways by which those nanoparticles alter redox equilibrium, augment the intrinsic sensitivity of neurons to neuroinflammation, and provoke a rise of Aβ peptides. By identifying signaling cascades dysregulated by TiO2- and CB-NPs in neurons, our data shed light on how human exposure to some NPs might be related to AD.

Dataset Information

Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats.

Publications

Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats.

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