Variation in the Composition and In Vitro Proinflammatory Effect of Urban Particulate Matter from Different Sites

Spatial variation in particulate matter–related health and toxicological outcomes is partly due to its composition. We studied spatial variability in particle composition and induced cellular responses in Mexico City to complement an ongoing epidemiologic study. We measured elements, endotoxins, and polycyclic aromatic hydrocarbons in two particle size fractions collected in five sites. We compared the in vitro proinflammatory response of J774A.1 and THP‐1 cells after exposure to particles, measuring subsequent TNFα and IL‐6 secretion. Particle composition varied by site and size. Particle constituents were subjected to principal component analysis, identifying three components: C 1 (Si, Sr, Mg, Ca, Al, Fe, Mn, endotoxin), C 2 (polycyclic aromatic hydrocarbons), and C 3 (Zn, S, Sb, Ni, Cu, Pb). Induced TNFα levels were higher and more heterogeneous than IL‐6 levels. Cytokines produced by both cell lines only correlated with C 1 , suggesting that constituents associated with soil induced the inflammatory response and explain observed spatial differences. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:87‐97, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21471Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96321/1/jbt21471.pd

Nanomaterials Versus Ambient Ultrafine Particles: An Opportunity to Exchange Toxicology Knowledge

BACKGROUND: A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions in in vitro models. OBJECTIVES: NMs are available with a range of physicochemical characteristics, which allows a more systematic toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm in diameter) provides an opportunity to identify plausible health effects for NMs, and the study of NMs provides an opportunity to facilitate the understanding of the mechanism of toxicity of UFP. METHODS: A workshop of experts systematically analyzed the available information and identified 19 key lessons that can facilitate knowledge exchange between these discipline areas. DISCUSSION: Key lessons range from the availability of specific techniques and standard protocols for physicochemical characterization and toxicology assessment to understanding and defining dose and the molecular mechanisms of toxicity. This review identifies a number of key areas in which additional research prioritization would facilitate both research fields simultaneously. CONCLUSION: There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa.info:eu-repo/semantics/publishedVersio

Synthesis, Characterization and In Vitro Study of Synthetic and Bovine-Derived Hydroxyapatite Ceramics: A Comparison

The physicochemical properties and biological behavior of sintered-bovine-derived hydroxyapatite (BHAp) are here reported and compared to commercial synthetic-HAp (CHAp). Dense ceramics were sintered for 2 h and 4 h at 1200 °C to investigate their microstructure–structure–in-vitro behavior relationship for both HAp ceramics. Densification was directly proportional to sintering time, showing a grain coarsening behavior with a greater effect on BHAp. Lattice parameters, crystallite size, cell volume and Ca/P ratio were determined by Rietveld refinement of X-ray diffraction (XRD) patterns using GSAS®. Ionic substitutions (Na+, Mg2+, CO32−) related to BHAp structure were associated with their position changes in the vibrational modes and correlated with the structural parameters obtained from the XRD analysis. Variations in the structural parameters and surface morphology were also evaluated after different soaking periods in simulated body fluid, which is associated with the formation of bone-like apatite layer and thus bioactivity. Mitochondrial activity (MTS) and lactate dehydrogenase (LDH) assays showed that the material released by the ceramics does not induce toxicity after exposure in human fetal osteoblastic (hFOB) cells. Furthermore, no statistically significant differences were found between the HAp obtained from different sources. These results show that BHAp can be used with no restrictions for the same biomedical applications as CHAp

Aluminum enhances the oxidative damage of ZnO NMs in the human neuroblastoma SH-SY5Y cell line.

Bare and doped zinc oxide nanomaterials (ZnO NMs) are of great interest as multifunctional platforms for biomedical applications. In this study, we systematically investigate the physicochemical properties of Aluminum doped ZnO (AZO) and its bio-interactions with neuroblastoma (SH-SY5Y) and red blood (RBCs) cells. We provide a comprehensive chemical and structural characterization of the NMs. We also evaluated the biocompatibility of AZO NMs using traditional toxicity assays and advanced microscopy techniques. The toxicity of AZO NMs towards SH-SY5Y cells, decreases as a function of Al doping but is higher than the toxicity of ZnO NMs. Our results show that N-acetyl cysteine protects SH-SY5Y cells against reactive oxygen species toxicity induced by AZO NMs. ZnO and AZO NMs do not exert hemolysis in human RBCs at the doses that cause toxicity (IC50) in neuroblastoma cells. The Atomic force microscopy qualitative analysis of the interaction of SH-SY5Y cells with AZO NMs shows evidence that the affinity of the materials with the cells results in morphology changes and diminished interactions between neighboring cells. The holotomographic microscopy analysis demonstrates NMs internalization in SH-SY5Y cells, changes in their chemical composition, and the role of lipid droplets in the clearance of toxicants

Aluminum enhances the oxidative damage of ZnO NMs in the human neuroblastoma SH-SY5Y cell line

Abstract Bare and doped zinc oxide nanomaterials (ZnO NMs) are of great interest as multifunctional platforms for biomedical applications. In this study, we systematically investigate the physicochemical properties of Aluminum doped ZnO (AZO) and its bio-interactions with neuroblastoma (SH-SY5Y) and red blood (RBCs) cells. We provide a comprehensive chemical and structural characterization of the NMs. We also evaluated the biocompatibility of AZO NMs using traditional toxicity assays and advanced microscopy techniques. The toxicity of AZO NMs towards SH-SY5Y cells, decreases as a function of Al doping but is higher than the toxicity of ZnO NMs. Our results show that N-acetyl cysteine protects SH-SY5Y cells against reactive oxygen species toxicity induced by AZO NMs. ZnO and AZO NMs do not exert hemolysis in human RBCs at the doses that cause toxicity (IC50) in neuroblastoma cells. The Atomic force microscopy qualitative analysis of the interaction of SH-SY5Y cells with AZO NMs shows evidence that the affinity of the materials with the cells results in morphology changes and diminished interactions between neighboring cells. The holotomographic microscopy analysis demonstrates NMs' internalization in SH-SY5Y cells, changes in their chemical composition, and the role of lipid droplets in the clearance of toxicants. Graphical Abstrac

In utero exposure to ultrafine particles promotes placental stress-induced programming of renin-angiotensin system-related elements in the offspring results in altered blood pressure in adult mice

Abstract Background Exposure to particulate matter (PM) is associated with an adverse intrauterine environment, which can promote adult cardiovascular disease (CVD) risk. Ultrafine particles (UFP) (small size and large surface area/mass ratio) are systemically distributed, induce inflammation and oxidative stress, and have been associated with vascular endothelial dysfunction and arterial vasoconstriction, increasing hypertension risk. Placental stress and alterations in methylation of promoter regions of renin-angiotensin system (RAS)-related elements could be involved in UFP exposure-related programming of hypertension. We investigated whether in utero UFP exposure promotes placental stress by inflammation and oxidative stress, alterations in hydroxysteroid dehydrogenase 11b-type 2 (HSD11B2) and programming of RAS-related elements, and result in altered blood pressure in adult offspring. UFP were collected from ambient air using an aerosol concentrator and physicochemically characterized. Pregnant C57BL/6J p un/p un female mice were exposed to collected UFP (400 μg/kg accumulated dose) by intratracheal instillation and compared to control (nonexposed) and sterile H2O (vehicle) exposed mice. Embryo reabsorption and placental stress by measurement of the uterus, placental and fetal weights, dam serum and fetal cortisol, placental HSD11B2 DNA methylation and protein levels, were evaluated. Polycyclic aromatic hydrocarbon (PAH) biotransformation (CYP1A1 and NQO1 (NAD(P)H dehydrogenase (quinone)1)) enzymes, inflammation and oxidative stress in placentas and fetuses were measured. Postnatal day (PND) 50 in male offspring blood pressure was measured. Methylation and protein expression of (RAS)-related elements, angiotensin II receptor type 1 (AT1R) and angiotensin I-converting enzyme (ACE) in fetuses and lungs of PND 50 male offspring were also assessed. Results In utero UFP exposure induced placental stress as indicated by an increase in embryo reabsorption, decreases in the uterus, placental, and fetal weights, and HSD11B2 hypermethylation and protein downregulation. In utero UFP exposure induced increases in the PAH-biotransforming enzymes, intrauterine oxidative damage and inflammation and stimulated programming and activation of AT1R and ACE, which resulted in increased blood pressure in the PND 50 male offspring. Conclusions In utero UFP exposure promotes placental stress through inflammation and oxidative stress, and programs RAS-related elements that result in altered blood pressure in the offspring. Exposure to UFP during fetal development could influence susceptibility to CVD in adulthood

Effect of subchronic exposure to ambient fine and ultrafine particles on rat motor activity and ex vivo striatal dopaminergic transmission

Alterations in dopaminergic transmission are associated with neurological disorders, such as depression, autism, and Parkinson's disease. Exposure of rats to ambient fine (FP) or ultrafine (UFP) particles induces oxidative and inflammatory responses in the striatum, a neuronal nucleus with dense dopaminergic innervation and critically involved in the control of motor activity.Objectives: We used an ex vivo system to evaluate the effect of in&nbsp;vivo inhalation exposure to FP and UFP on motor activity and dopaminergic transmission.Materials and Methods: Male adult Wistar rats were exposed to FP, UFP, or filtered air for 8 weeks (subchronic exposure; 5 h/day, 5 days/week) in a particle concentrator. Motor activity was evaluated using the open-field test. Uptake and release of [3H]-dopamine were assessed in striatal synaptosomes, and dopamine D2 receptor (D2R) affinity for dopamine was evaluated by the displacement of [3H]-spiperone binding to striatal membranes.Results: Exposure to FP or UFP significantly reduced spontaneous motor activity (ambulatory distance: FP -25%, UFP -32%; ambulatory time: FP -24%, UFP -22%; ambulatory episodes: FP -22%, UFP -30%), decreased [3H]-dopamine uptake (FP -18%, UFP -24%), and increased, although not significantly, [3H]-dopamine release (113.3 ± 16.3 and 138.6 ± 17.3%). Neither FP nor UFP exposure affected D2R density or affinity for dopamine.Conclusions: These results indicate that exposure to ambient particulate matter reduces locomotion in rats, which could be related to altered striatal dopaminergic transmission: UFP was more potent than FP. Our results contribute to the evidence linking environmental factors to changes in brain function that could turn into neurological and psychiatric disorders.HIGHLIGHTSYoung adult rats were exposed to fine (FP) or ultrafine (UFP) particles for 40 days.Exposure to FP or UFP reduced motor activity.Exposure to FP or UFP reduced dopamine uptake by striatal synaptosomes.Neither D2R density or affinity for dopamine was affected by FP or UFP.UFP was more potent than FP to exert the effects reported