Acellular oxidative potential assay for screening of amorphous silica nanoparticles.

Silica nanoparticles (SiNPs) are used in a wide range of consumer products, engineering and medical applications, with likelihood of human exposure and potential health concerns. It is essential to generate toxicity information on SiNP forms and associated physicochemical determinants to conduct risk assessment on these new materials. To address this knowledge gap, we screened a panel of custom synthesized, well-characterized amorphous SiNPs pristine and surface-modified (-C3-COOH, -C11-COOH, -NH, -PEG) of 5 different sizes: (15, 30, 50, 75, 100 nm) for their oxidative potential using an acellular assay.

Physicochemical Properties Can Be Key Determinants of Mesoporous Silica Nanoparticle Potency in Vitro.

Nanoforms of mesoporous silica (mSiNPs) are increasingly applied in medicine, imaging, energy storage, catalysis, biosensors, and bioremediation. The impact of their physicochemical properties on health and the environment remain to be elucidated. In this work, newly synthesized mesoporous silica (sizes: 25, 70, 100, 170, and 600 nm; surface functionalization: pristine, C3-, and C11-COOH moieties) were assessed for cytotoxicity and induction of inflammatory responses in vitro (A549, THP-1, J774A.

A matrix-assisted laser desorption ionization-time-of-flight-time-of-flight-mass spectrometry-based toxicoproteomic screening method to assess in vitro particle potencies.

Knowledge of biological reactivity and underlying toxicity mechanisms of airborne particulate matter (PM) is central to the characterization of the risk associated with these pollutants. An integrated screening platform consisting of protein profiling of cellular responses and cytotoxic analysis was developed in this study for the estimation of PM potencies. Mouse macrophage (J774A.

Differential cytotoxic and inflammatory potency of amorphous silicon dioxide nanoparticles of similar size in multiple cell lines.

The likelihood of environmental and health impacts of silicon dioxide nanoparticles (SiNPs) has risen, due to their increased use in products and applications. The biological potency of a set of similarly-sized amorphous SiNPs was investigated in a variety of cells to examine the influence of physico-chemical and biological factors on their toxicity. Cellular LDH and ATP, BrdU incorporation, resazurin reduction and cytokine release were measured in human epithelial A549, human THP-1 and mouse J774A.

Contrasting biological potency of particulate matter collected at sites impacted by distinct industrial sources.

Background: Industrial sources contribute a significant proportion of anthropogenic particulate matter (PM) emissions, producing particles of varying composition that may differentially impact health. This study investigated the in vitro toxicity of ambient PM collected near industrial sites in relation to particle size and composition.

Methods: Size-fractionated particles (ultrafine, PM, PM, PM) were collected in the vicinity of steel, copper, aluminium, and petrochemical industrial sites.

Development of an integrated approach for comparison of in vitro and in vivo responses to particulate matter.

Background: Association of particulate matter with adverse health effects has been established in epidemiological studies and animal experiments. Epidemiological studies are difficult to undertake while animal studies are impractical for high-throughput toxicity testing. The ease and rapidity of in vitro tests emphasizes their potential for use in risk assessment of chemicals and particles.

Blood metal levels and third trimester maternal plasma matrix metalloproteinases (MMPs).

While it is known that in utero exposure to environmental toxicants, namely heavy metals, can adversely affect the neonate, there remains a significant paucity of information on maternal biological changes specific to metal exposures during pregnancy. This study aims at identifying associations between maternal metal exposures and matrix metalloproteinases (MMPs) that are known to be engaged in pregnancy process. Third trimester maternal plasma (n = 1533) from a pregnancy cohort (Maternal-Infant Research on Environmental Chemicals Study, MIREC) were analyzed for MMP-1,-2,-7,-9 and -10 by affinity-based multiplex protein array analyses.

Impact of Superoxide Dismutase Mimetic AEOL 10150 on the Endothelin System of Fischer 344 Rats.

Endothelin-1 is a potent vasoconstrictor and mitogenic peptide involved in the regulation of vasomotor tone and maintenance of blood pressure. Oxidative stress activates the endothelin system, and is implicated in pulmonary and cardiovascular diseases including hypertension, congestive heart failure, and atherosclerosis. Superoxide dismutase mimetics designed with the aim of treating diseases that involve reactive oxygen species in their pathophysiology may exert a hypotensive effect, but effects on the endothelin system are unknown.

Nitrative stress, oxidative stress and plasma endothelin levels after inhalation of particulate matter and ozone.

Background: While exposure to ambient air contaminants is clearly associated with adverse health outcomes, disentangling mechanisms of pollutant interactions remains a challenge.

Objectives: We aimed at characterizing free radical pathways and the endothelinergic system in rats after inhalation of urban particulate matter, ozone, and a combination of particles plus ozone to gain insight into pollutant-specific toxicity mechanisms and any effect modification due to air pollutant mixtures.

Methods: Fischer 344 rats were exposed for 4 h to a 3 × 3 concentration matrix of ozone (0, 0.

Cytotoxic and inflammatory potential of size-fractionated particulate matter collected repeatedly within a small urban area.

Background: Exposure to coarse, fine, and ultrafine particles is associated with adverse population health impacts. We investigated whether size-fractionated particles collected repeatedly in the vicinity of industrial (steel mills and associated coking operations, wastewater treatment), high traffic, and residential areas display systematic differences in biological potency.

Methods: Particulate matter (PM<0.

Correlation between Saliva and Plasma Levels of Endothelin Isoforms ET-1, ET-2, and ET-3.

Although saliva endothelins are emerging as valuable noninvasive cardiovascular biomarkers, reports on the relationship between isoforms in saliva and plasma remain scarce. We measured endothelins in concurrent saliva and plasma samples (n = 30 males; age 18-63) by HPLC-fluorescence. Results revealed statistically significant positive correlations among all isoforms between saliva and plasma: big endothelin-1 (BET-1, 0.

Cytotoxicity of carbon nanotube variants: a comparative in vitro exposure study with A549 epithelial and J774 macrophage cells.

While production of engineered carbon nanotubes (CNTs) has escalated in recent years, knowledge of risk associated with exposure to these materials remains unclear. We report on the cytotoxicity of four CNT variants in human lung epithelial cells (A549) and murine macrophages (J774). Morphology, metal content, aggregation/agglomeration state, pore volume, surface area and modifications were determined for the pristine and oxidized single-walled (SW) and multi-walled (MW) CNTs.

Nitrogen dioxide and ultrafine particles dominate the biological effects of inhaled diesel exhaust treated by a catalyzed diesel particulate filter.

We studied the impact of a catalyzed diesel particulate filter (DPF) on the toxicity of diesel exhaust. Rats inhaled exhaust from a Cummins ISM heavy-duty diesel engine, with and without DPF after-treatment, or HEPA-filtered air for 4h, on 1 day (single exposure) and 3 days (repeated exposures). Biological effects were assessed after 2h (single exposure) and 20h (single and repeated exposures) recovery in clean air.

Cardiovascular changes in atherosclerotic ApoE-deficient mice exposed to Co60 (γ) radiation.

Background: There is evidence for a role of ionizing radiation in cardiovascular diseases. The goal of this work was to identify changes in oxidative and nitrative stress pathways and the status of the endothelinergic system during progression of atherosclerosis in ApoE-deficient mice after single and repeated exposure to ionizing radiation.

Methods And Results: B6.

Current status and future perspectives of mass spectrometry imaging.

Mass spectrometry imaging is employed for mapping proteins, lipids and metabolites in biological tissues in a morphological context. Although initially developed as a tool for biomarker discovery by imaging the distribution of protein/peptide in tissue sections, the high sensitivity and molecular specificity of this technique have enabled its application to biomolecules, other than proteins, even in cells, latent finger prints and whole organisms. Relatively simple, with no requirement for labelling, homogenization, extraction or reconstitution, the technique has found a variety of applications in molecular biology, pathology, pharmacology and toxicology.

Respiratory burst in alveolar macrophages exposed to urban particles is not a predictor of cytotoxicity.

We examined the utility of respiratory burst measurements in alveolar macrophages to assess adverse cellular changes following exposure to urban particles. Cells were obtained by bronchioalveolar lavage of Fisher 344 rats and exposed (0-100 μg/well) to urban particles (EHC-93, SRM-1648, SRM-1649, PM2.5), the soluble (EHC-93sol) and insoluble (EHC-93insol) fractions of EHC-93 (EHC-93tot), mineral particles (TiO(2), SiO(2)) and metal oxides (iron III oxide, iron II/III oxide, copper II oxide, nickel II oxide).

Assessment of suitability of magnetic beads for purification of rat plasma in proteomic analyses by matrix-assisted laser desorption ionization-time-of-flight MS.

Plasma is a complex matrix and has to be clarified or fractionated to obtain informative MS data. Although there are a number of prefractionation methods to clean up complex biological matrixes before proteomic analysis, these methods require large sample volumes and are costly and time-consuming. Alternatively, recently introduced magnetic beads (MB) appear to be attractive in overcoming these difficulties.

A high performance liquid chromatography-electrochemical array method for the measurement of oxidative/nitrative changes in human urine.

Oxidative stress has been implicated in various pathologies as well as in environmental pollutant-induced negative health outcomes. In this work we have developed an analytical method to measure oxidative stress markers namely m-, o-tyrosine, 3-chlorotyrosine, 3-nitrotyrosine, and the DNA damage marker 8-hydroxy deoxyguanosine in human urine. The method involves the base hydrolysis of the urine sample followed by solid phase extraction of target analytes using a reverse phase polymeric sorbent column prior to the HPLC-EC analysis.

Effects of a cyclooxygenase-2 preferential inhibitor in young healthy dogs exposed to air pollution: a pilot study.

Residency in cities with high air pollution is associated with neuroinflammation and neurodegeneration in healthy children, young adults, and dogs. Nonsteroidal anti-inflammatory drugs may offer neuroprotection. The authors measured the plasma concentrations of 3-nitrotyrosine and the cerebro-spinal-fluid concentrations of prostaglandin E2 metabolite and the oligomeric form of amyloid derived diffusible ligand; measured the mRNA expression of cyclooxygenase-2, interleukin 1beta, CD14, and Aquaporin-4 in target brain areas; and evaluated brain MRI, cognition, and neuropathology in 8 dogs treated with a preferential cyclooxygenase-2 inhibitor (Nimesulide) versus 7 untreated litter-matched Mexico City dogs.

Changes in red cell ion transport, reduced intratumoral neovascularization, and some mild motor function abnormalities accompany targeted disruption of the Mouse Kell gene (Kel).

Kell (ECE-3), a highly polymorphic blood group glycoprotein, displays more than 30 antigens that produce allo-antibodies and, on red blood cells (RBCs), is complexed through a single disulfide bond with the integral membrane protein, XK. XK is a putative membrane transporter whose absence results in a late onset form of neuromuscular abnormalities known as the McLeod syndrome. Although Kell glycoprotein is known to be an endothelin-3-converting enzyme, the full extent of its physiological function is unknown.

Air pollution alters brain and pituitary endothelin-1 and inducible nitric oxide synthase gene expression.

Recent work suggests that air pollution is a risk factor for cerebrovascular and neurodegenerative disease. Effects of inhaled pollutants on the production of vasoactive factors such as endothelin (ET) and nitric oxide (NO) in the brain may be relevant to disease pathogenesis. Inhaled pollutants increase circulating levels of ET-1 and ET-3, and the pituitary is a potential source of plasma ET, but the effects of pollutants on the expression of ET and NO synthase genes in the brain and pituitary are not known.

Pulmonary expression of preproET-1 and preproET-3 mRNAs is altered reciprocally in rats after inhalation of air pollutants.

Perturbation of vascular homeostasis is an important mechanism related to the acute health effects of inhaled pollutants. Inhalation of urban particulate matter and ozone by rats has been shown to result in increased synthesis of the potent vasoactive peptide endothelin (ET)-1 in the lungs, with spillover into the circulation. In the present work, we have analyzed the interrelationships between responses of the three major endothelin isoforms, ET-1[1-21], ET-2[1-21], and ET-3[1-21], to inhaled pollutants at the peptide and gene expression levels.

Differential regulation of the lung endothelin system by urban particulate matter and ozone.

Periodic elevation of ambient particulate matter and ozone levels is linked to acute cardiac morbidity and mortality. Increased plasma levels of the potent vasoconstrictor endothelin (ET)-1, a prognostic indicator of cardiac mortality, have been detected in both animal models and humans after exposure to air pollutants. The lungs are the primary source of circulating ET-1, but the direct effects of individual air pollutants and their interaction in modulating the pulmonary endothelin system are unknown.

Air pollutants increase gene expression of the vasoconstrictor endothelin-1 in the lungs.

Inhalation of urban pollutants elevates the circulating levels of the vasoactive peptides endothelin (ET)-1 and ET-3 in rats. This effect could explain the association between episodic variations of urban pollutants and acute cardiopulmonary morbidity and mortality documented in epidemiological studies. Because the lungs are the primary source of circulating ET-1 and the main site of clearance from circulation, we investigated the response of endothelin system genes in the lungs of Fischer-344 rats after 4-h nose-only inhalation of 0.