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Valdiglesias V.,University of La Coruna | Costa C.,Portuguese National Institute of Health | Sharma V.,Indian Institute of Toxicology Research | Kilic G.,University of La Coruna | And 5 more authors.
Food and Chemical Toxicology

Titanium dioxide (TiO2) are among most frequently used nanoparticles (NPs). They are present in a variety of consumer products, including food industry in which they are employed as an additive. The potential toxic effects of these NPs on mammal cells have been extensively studied. However, studies regarding neurotoxicity and specific effects on neuronal systems are very scarce and, to our knowledge, no studies on human neuronal cells have been reported so far. Therefore, the main objective of this work was to investigate the effects of two types of TiO2 NPs, with different crystalline structure, on human SHSY5Y neuronal cells. After NPs characterization, a battery of assays was performed to evaluate the viability, cytotoxicity, genotoxicity and oxidative damage in TiO2 NP-exposed SHSY5Y cells. Results obtained showed that the behaviour of both types of NPs resulted quite comparable. They did not reduce the viability of neuronal cells but were effectively internalized by the cells and induced dose-dependent cell cycle alterations, apoptosis by intrinsic pathway, and genotoxicity not related with double strand break production. Furthermore, all these effects were not associated with oxidative damage production and, consequently, further investigations on the specific mechanisms underlying the effects observed in this study are required. © 2013 Elsevier Ltd. Source

Valdiglesias V.,University of La Coruna | Kilic G.,University of La Coruna | Costa C.,Portuguese National Institute of Health | Costa C.,University of Porto | And 5 more authors.
Environmental and Molecular Mutagenesis

Iron oxide nanoparticles (ION) with superparamagnetic properties hold great promise for use in various biomedical applications; specific examples include use as contrast agents for magnetic resonance imaging, in targeted drug delivery, and for induced hyperthermia cancer treatments. Increasing potential applications raise concerns over their potential effects on human health. Nevertheless, very little is currently known about the toxicity associated with exposure to these nanoparticles at different levels of biological organization. This article provides an overview of recent studies evaluating ION cytotoxicity, genotoxicity, developmental toxicity and neurotoxicity. Although the results of these studies are sometimes controversial, they generally indicate that surface coatings and particle size seem to be crucial for the observed ION-induced effects, as they are critical determinants of cellular responses and intensity of effects, and influence potential mechanisms of toxicity. The studies also suggest that some ION are safe for certain biomedical applications, while other uses need to be considered more carefully. Overall, the available studies provide insufficient evidence to fully assess the potential risks for human health related to ION exposure. Additional research in this area is required including studies on potential long-term effects. © 2014 Wiley Periodicals, Inc. Source

Carvalho V.,IBB Institute for Biotechnology And Bioengineering | Castanheira P.,Molecular Biotechnology Unit | Madureira P.,Abel Salazar Biomedical Sciences Institute | Madureira P.,Institute Biologia Molecular e Celular | And 8 more authors.
Biotechnology and Bioengineering

Interleukin-10 (IL-10) is an anti-inflammatory cytokine, which active form is a non-covalent homodimer. Given the potential of IL-10 for application in various medical conditions, it is essential to develop systems for its effective delivery. In previous work, it has been shown that a dextrin nanogel effectively incorporated and stabilized rIL-10, enabling its release over time. In this work, the delivery system based on dextrin nanogels was further analyzed. The biocompatibility of the nanogel was comprehensively analyzed, through cytotoxicity (lactate dehydrogenase (LDH) release, MTS, Live, and Dead) and genotoxicity (comet) assays. The release profile of rIL-10 and its biological activity were evaluated in vivo, using C57BL/6 mice. Although able to maintain a stable concentration of IL-10 for at least 4h in mice serum, the amount of protein released was rather low. Despite this, the amount of rIL-10 released from the complex was biologically active inhibiting TNF-α production, in vivo, by LPS-challenged mice. In spite of the significant stabilization achieved using the nanogel, rIL-10 still denatures rather quickly. An additional effort is thus necessary to develop an effective delivery system for this cytokine, able to release active protein over longer periods of time. Nevertheless, the good biocompatibility, the protein stabilization effect and the ability to perform as a carrier with controlled release suggest that self-assembled dextrin nanogels may be useful protein delivery systems. © 2011 Wiley Periodicals, Inc. Source

Kilic G.,University of La Coruna | Costa C.,Portuguese National Institute of Health | Costa C.,University of Porto | Fernandez-Bertolez N.,University of La Coruna | And 5 more authors.
Toxicology Research

Iron oxide nanoparticles (ION) have been widely used in biomedical applications, for both diagnosis and therapy, due to their unique magnetic properties. They are intensively explored in neuromedicine mostly because of their ability to cross the blood brain barrier. Hence, their potential harmful effects on neuronal cells need to be carefully assessed. The objective of this study was to evaluate the toxicity of silica-coated ION (S-ION) (10-200 μg ml-1) on human neuronal SHSY5Y cells. Alterations in the cell cycle, cell death by apoptosis or necrosis, and membrane integrity were assessed as cytotoxicity parameters. Genotoxicity was determined by a γH2AX assay, a micronucleus (MN) test, and a comet assay. Complementarily, possible effects on DNA damage repair were also analysed by means of a DNA repair competence assay. All analyses were performed in complete and serum-free cell culture media. Iron ion release from the nanoparticles was notable only in complete medium. Despite being effectively internalized by the neuronal cells, S-ION presented in general low cytotoxicity; positive results were only obtained in some assays at the highest concentrations and/or the longest exposure time tested (24 h). Genotoxicity evaluations in serum-free medium were negative for all conditions assayed; in complete medium, dose and time-dependent increase in DNA damage not related to the production of double strand breaks or chromosome loss (according to the results of the γH2AX assay and MN test), was obtained. The presence of serum slightly influenced the behaviour of S-ION; further studies to investigate the formation of a protein corona and its role in nanoparticle toxicity are necessary. © The Royal Society of Chemistry 2016. Source

Tchepel O.,University of Coimbra | Dias D.,University of Coimbra | Costa C.,Portuguese National Institute of Health | Costa C.,University of Porto | And 3 more authors.
Journal of Toxicology and Environmental Health - Part A: Current Issues

Urban areas characterized by high spatial and temporal variability in air pollution levels require implementation of comprehensive approaches to address exposure of individuals. The main objective of this study was to implement a quantitative assessment of individual exposure to benzene in urban environments. For this purpose, ExPOSITION model based on a global positioning system (GPS) tracking approach was applied to estimate individual exposure in different microenvironments. The current investigation provides an application example and validation of the modeling approach against personal and biological exposure measurements collected during the measurements campaign. The probabilistic approach using the Johnson system of distributions was implemented to characterize variability of indoor concentrations. The results obtained for daily average individual exposure to benzene corresponded to mean levels of 1.6 and 0.8-2.7 μg/m3 in terms of 5th-95th percentiles. Validation of the model results against several personal exposure samples collected for the selected individuals revealed a Pearsons correlation coefficient of.66. This modeling approach explicitly addressed the temporal and spatial variability in the exposure and established a source-receptor relationship. Copyright © 2014 Taylor & Francis Group, LLC. Source

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