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

Distribution, Toxicity and Mode of Action of The Novel Copper-Based Anticancer Compound: Casiopeina II.

The in vivo fate and toxicity of the novel copper-based anticancer agent casiopeina II ([Cu(4,7-dimethyl-l,10-phenanthroline)(glycine)NO3]), and in vitro mode of cell death induced in two cancer cell lines were investigated. After a single intravenous administration of 3H-casiopeina II (5mg/kg dose) in the rat the complex was rapidly distributed to tissues, the 3H-phenanthroline was excreted via urine and faeces whilst the copper appeared to be predominantly retained with a small amount being excreted via faeces. Differences in tissue copper retention and 3H-phenanthroline elimination suggest an in vivo dissociation of the complex. The major toxic effect attributed to casiopeina II administration was haemolytic anaemia (reduced haemoglobin concentration, red blood cell count and packed cell volume as well as leukocytosis and neutrophilia) observed at 12 hours and 5 days after administration can be attributable to direct erythrocyte oxidative damage. Increased reticulocyte levels and the presence of normoblasts in peripheral blood 5 days after administration indicated an effective erythropoietic response and tendency towards recovery at 15 days. Increase in spleen weight was attributed to an increased uptake of damaged erythrocytes by the reticuloendothelial system. Older rats (10-week old) appeared to be more susceptible to the haemolytic damage than younger rats (6-week old) possibly due to a reduced erythrocytic tolerance. Erythropoietin pretreament before casiopeina II administration reduced the haematological effects. Cell death by apoptosis, induced in vitro in CH1 human ovarian carcinoma and L1210 murine leukaemia cells after casiopeina II treatment, was observed by cell morphology, DNA integrity and caspase activation. Cisplatin resistant and susceptible forms of CH1 and L1210 cells were equally sensitive to casiopeina II apoptosis induction. The mechanism by which casiopeina II activates caspases in the two cell lines, although unclear, suggests an intracellular trigger such as intramitochondrial ROS generation by the Cu(II) moiety of casiopeina II

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