RESUMO
Exposure to asbestos and asbestos-like minerals has been related to the development of severe lung diseases, including cancer and malignant mesothelioma (MM). A high incidence of non-occupational MM was observed in New Caledonia (France) in people living in proximity of serpentinite outcrops, containing chrysotile and fibrous antigorite. Antigorite is a magnesium silicate, which shares with chrysotile asbestos the chemical formula. To achieve information on antigorite toxicity, we investigated the physico-minero-chemical features relevant for toxicity and cellular effects elicited on murine macrophages (MH-S) and alveolar epithelial cells (A549) of three fibrous antigorites (f-Atg) collected in a Caledonian nickel lateritic ore and subjected to supergene alteration. Field Atg were milled to obtain samples suitable for toxicological studies with a similar particle size distribution. UICC chrysotile (Ctl) and a non-fibrous antigorite (nf-Atg) were used as reference minerals. A high variability in toxicity was observed depending on shape, chemical alteration, and surface reactivity. The antigorites shared with Ctl a similar surface area (16.3, 12.1, 20.3, 13.4, and 15.6 m2/g for f-Atg1, 2, 3, nf-Atg, and Ctl). f-Atg showed different level of pedogenetic weathering (Ni depletion f-Atg1 ⪠f-Atg2 and 3) and contained about 50% of elongated mineral particles, some of which exhibited high aspect ratios (AR > 10 µm, 20%, 26%, 31% for f-Atg1, 2, and 3, respectively). The minerals differed in bio-accessible iron at pH 4.5 (f-Atg1 ⪠f-Atg3, < f-Atg2, nf-Atg < Ctl), and surface reactivity (ROS release in solution, f-Atg1 ⪠f-Atg2, 3, nf-Atg, and Ctl). f-Atg2 and f-Atg3 induced oxidative stress and pro-inflammatory responses, while the less altered, poorly reactive sample (f-Atg1) induced negligible effects, as well nf-Atg. The slow dissolution kinetics observed in simulated body fluids may signal a high biopersistence. Overall, our work revealed a significative cellular toxicity of f-Atg that correlates with fibrous habit and surface reactivity.
Assuntos
Asbestos Serpentinas , Amianto , Humanos , Camundongos , Animais , Asbestos Serpentinas/toxicidade , Nova Caledônia , Amianto/toxicidade , Minerais/toxicidade , SilicatosRESUMO
Inhalation of silica particles can induce inflammatory lung reactions that lead to silicosis and/or lung cancer when the particles are biopersistent. This toxic activity of silica dusts is extremely variable depending on their source and preparation methods. The exact molecular moiety that explains and predicts this variable toxicity of silica remains elusive. Here, we have identified a unique subfamily of silanols as the major determinant of silica particle toxicity. This population of "nearly free silanols" (NFS) appears on the surface of quartz particles upon fracture and can be modulated by thermal treatments. Density functional theory calculations indicates that NFS locate at an intersilanol distance of 4.00 to 6.00 Å and form weak mutual interactions. Thus, NFS could act as an energetically favorable moiety at the surface of silica for establishing interactions with cell membrane components to initiate toxicity. With ad hoc prepared model quartz particles enriched or depleted in NFS, we demonstrate that NFS drive toxicity, including membranolysis, in vitro proinflammatory activity, and lung inflammation. The toxic activity of NFS is confirmed with pyrogenic and vitreous amorphous silica particles, and industrial quartz samples with noncontrolled surfaces. Our results identify the missing key molecular moieties of the silica surface that initiate interactions with cell membranes, leading to pathological outcomes. NFS may explain other important interfacial processes involving silica particles.
Assuntos
Silanos/química , Dióxido de Silício/química , Dióxido de Silício/toxicidade , Membrana Celular , Cristalização , Poeira , Tamanho da Partícula , Quartzo/química , Quartzo/toxicidade , Propriedades de SuperfícieRESUMO
BACKGROUND: Silica continues to represent an intriguing topic of fundamental and applied research across various scientific fields, from geology to physics, chemistry, cell biology, and particle toxicology. The pathogenic activity of silica is variable, depending on the physico-chemical features of the particles. In the last 50 years, crystallinity and capacity to generate free radicals have been recognized as relevant features for silica toxicity. The 'surface' also plays an important role in silica toxicity, but this term has often been used in a very general way, without defining which properties of the surface are actually driving toxicity. How the chemical features (e.g., silanols and siloxanes) and configuration of the silica surface can trigger toxic responses remains incompletely understood. MAIN BODY: Recent developments in surface chemistry, cell biology and toxicology provide new avenues to improve our understanding of the molecular mechanisms of the adverse responses to silica particles. New physico-chemical methods can finely characterize and quantify silanols at the surface of silica particles. Advanced computational modelling and atomic force microscopy offer unique opportunities to explore the intimate interactions between silica surface and membrane models or cells. In recent years, interdisciplinary research, using these tools, has built increasing evidence that surface silanols are critical determinants of the interaction between silica particles and biomolecules, membranes, cell systems, or animal models. It also has become clear that silanol configuration, and eventually biological responses, can be affected by impurities within the crystal structure, or coatings covering the particle surface. The discovery of new molecular targets of crystalline as well as amorphous silica particles in the immune system and in epithelial lung cells represents new possible toxicity pathways. Cellular recognition systems that detect specific features of the surface of silica particles have been identified. CONCLUSIONS: Interdisciplinary research bridging surface chemistry to toxicology is progressively solving the puzzling issue of the variable toxicity of silica. Further interdisciplinary research is ongoing to elucidate the intimate mechanisms of silica pathogenicity, to possibly mitigate or reduce surface reactivity.
Assuntos
Silanos/química , Silanos/toxicidade , Dióxido de Silício/química , Dióxido de Silício/toxicidade , Animais , Apoptose/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Química Computacional , Células Epiteliais/efeitos dos fármacos , Humanos , Imunidade Inata/efeitos dos fármacos , Simulação de Dinâmica Molecular , Propriedades de Superfície , Canais de Cátion TRPV/metabolismoRESUMO
The variability of quartz hazard stands as one of the most puzzling issues in particle toxicology, notwithstanding the fact that silicosis, the most ancient occupational disease, was the very topic from which the study of the toxicity of particulates developed. Over the years, other adverse effects of silica particles (i.e., lung cancer and autoimmune diseases) were detected and described. However, a few gaps are still present in the physicochemical determinants and cellular pathways involved in the mechanisms of silica pathogenicity. In this perspective, we illustrate how pooling together studies in occupational health and nanotoxicology might fill such gaps, yielding a consistent picture of what imparts toxicity to a given silica source. Recent investigations have shown that crystallinity is not implied in the pathogenic process of silica per se, while patches of disorganized silanols at the surface of both crystalline and amorphous particles can promote membrane damage and inflammation, a process at the origin of silica-related diseases. Introducing these new findings into the accepted multistep model of silica pathogenicity, we obtain a picture of the chemical features of silica governing each cellular step in agreement with the outcomes of major previous studies. We ascribe the origin of the variability of silica hazard mainly to the distribution of various moieties at the particle surface, with silanols playing the major role. Toxicity turns out to be likely predictable by an ad hoc surface characterization. Tailored modifications of the surface can be envisaged to prepare safe materials or blunt toxicity in existing ones.
Assuntos
Dióxido de Silício/toxicidade , Animais , Humanos , Dióxido de Silício/química , Propriedades de SuperfícieRESUMO
In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials. The findings of this review, in general, affirm those of the original evaluation on the inadequate or limited evidence of carcinogenicity for most types of CNTs and CNFs at this time, and possible carcinogenicity of one type of CNT (MWCNT-7). The key evidence gaps to be filled by research include: investigation of possible associations between in vitro and early-stage in vivo events that may be predictive of lung cancer or mesothelioma, and systematic analysis of dose-response relationships across materials, including evaluation of the influence of physico-chemical properties and experimental factors on the observation of nonmalignant and malignant endpoints.
Assuntos
Testes de Carcinogenicidade , Nanofibras/toxicidade , Nanotubos de Carbono/toxicidade , Animais , HumanosRESUMO
BACKGROUND: The eruptions of Eyjafjallajökull (2010) and Grímsvötn (2011), Iceland, triggered immediate, international consideration of the respiratory health hazard of inhaling volcanic ash, and prompted the need to estimate the potential hazard posed by future eruptions of Iceland's volcanoes to Icelandic and Northern European populations. METHODS: A physicochemical characterization and toxicological assessment was conducted on a suite of archived ash samples spanning the spectrum of past eruptions (basaltic to rhyolitic magmatic composition) of Icelandic volcanoes following a protocol specifically designed by the International Volcanic Health Hazard Network. RESULTS: Icelandic ash can be of a respirable size (up to 11.3 vol.% < 4 µm), but the samples did not display physicochemical characteristics of pathogenic particulate in terms of composition or morphology. Ash particles were generally angular, being composed of fragmented glass and crystals. Few fiber-like particles were observed, but those present comprised glass or sodium oxides, and are not related to pathogenic natural fibers, like asbestos or fibrous zeolites, thereby limiting concern of associated respiratory diseases. None of the samples contained cristobalite or tridymite, and only one sample contained quartz, minerals of interest due to the potential to cause silicosis. Sample surface areas are low, ranging from 0.4 to 1.6 m2 g-1, which aligns with analyses on ash from other eruptions worldwide. All samples generated a low level of hydroxyl radicals (HOâ¢), a measure of surface reactivity, through the iron-catalyzed Fenton reaction compared to concurrently analyzed comparative samples. However, radical generation increased after 'refreshing' sample surfaces, indicating that newly erupted samples may display higher reactivity. A composition-dependent range of available surface iron was measured after a 7-day incubation, from 22.5 to 315.7 µmol m-2, with mafic samples releasing more iron than silicic samples. All samples were non-reactive in a test of red blood cell-membrane damage. CONCLUSIONS: The primary particle-specific concern is the potential for future eruptions of Iceland's volcanoes to generate fine, respirable material and, thus, to increase ambient PM concentrations. This particularly applies to highly explosive silicic eruptions, but can also hold true for explosive basaltic eruptions or discrete events associated with basaltic fissure eruptions.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Material Particulado/efeitos adversos , Silicatos/efeitos adversos , Erupções Vulcânicas/efeitos adversos , Poluentes Atmosféricos/análise , Humanos , Islândia , Tamanho da Partícula , Material Particulado/análise , Silicatos/análise , Erupções Vulcânicas/análiseRESUMO
BACKGROUND: Exposure to some - but not all - quartz particles is associated to silicosis, lung cancer and autoimmune diseases. What imparts pathogenicity to any single quartz source is however still unclear. Crystallinity and various surface features are implied in toxicity. Quartz dusts used so far in particle toxicology have been obtained by grinding rocks containing natural quartz, a process which affects crystallinity and yields dusts with variable surface states. To clarify the role of crystallinity in quartz pathogenicity we have grown intact quartz crystals in respirable size. METHODS: Quartz crystals were grown and compared with a fractured specimen obtained by grinding the largest synthetic crystals and a mineral quartz (positive control). The key physico-chemical features relevant to particle toxicity - particle size distribution, micromorphology, crystallinity, surface charge, cell-free oxidative potential - were evaluated. Membranolysis was assessed on biological and artificial membranes. Endpoints of cellular stress were evaluated on RAW 264.7 murine macrophages by High Content Analysis after ascertaining cellular uptake by bio-TEM imaging of quartz-exposed cells. RESULTS: Quartz crystals were grown in the submicron (n-Qz-syn) or micron (µ-Qz-syn) range by modulating the synthetic procedure. Independently from size as-grown quartz crystals with regular intact faces did not elicit cellular toxicity and lysosomal stress on RAW 264.7 macrophages, and were non-membranolytic on liposome and red blood cells. When fractured, synthetic quartz (µ-Qz-syn-f) attained particle morphology and size close to the mineral quartz dust (Qz-f, positive control) and similarly induced cellular toxicity and membranolysis. Fracturing imparted a higher heterogeneity of silanol acidic sites and radical species at the quartz surface. CONCLUSIONS: Our data support the hypothesis that the biological activity of quartz dust is not due to crystallinity but to crystal fragmentation, when conchoidal fractures are formed. Besides radical generation, fracturing upsets the expected long-range order of non-radical surface moieties - silanols, silanolates, siloxanes - which disrupt membranes and induce cellular toxicity, both outcomes associated to the inflammatory response to quartz.
Assuntos
Poluentes Atmosféricos/toxicidade , Poeira , Macrófagos/efeitos dos fármacos , Nanopartículas/toxicidade , Quartzo/toxicidade , Dióxido de Silício/toxicidade , Poluentes Atmosféricos/química , Animais , Biomarcadores/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/ultraestrutura , Sobrevivência Celular/efeitos dos fármacos , Fenômenos Químicos , Cristalização , Hemólise/efeitos dos fármacos , Humanos , Macrófagos/imunologia , Macrófagos/ultraestrutura , Camundongos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Fenômenos Físicos , Quartzo/química , Células RAW 264.7 , Dióxido de Silício/química , Propriedades de Superfície , Testes de ToxicidadeRESUMO
In the course of studies of the interaction of proteins with TiO2 nanoparticles, we have investigated the role of the medium employed in cellular tests, by measuring the variation of ζ-potential vs pH in the range 2-9 and bovine serum albumin adsorption on TiO2 P25 in the presence of either HEPES or PBS as buffers, both mimicking the physiological pH, but with different chemical nature. The two buffers yield remarkably dissimilar surface charges and protein uptake, i.e., they impart different surface characteristics to the particles which could affect the contact with cells or tissues. This may account for dissimilar toxicological outcomes among in vitro tests and particularly between in vitro vs in vivo tests, considering the high amount of phosphate ions present in body fluids.
Assuntos
HEPES/química , Nanopartículas/química , Fosfatos/química , Soroalbumina Bovina/química , Titânio/química , Testes de Toxicidade/métodos , Adsorção , Soluções Tampão , Técnicas de Cultura de Células , Concentração de Íons de Hidrogênio , Nanopartículas/toxicidade , Propriedades de Superfície , Titânio/toxicidadeRESUMO
Titanium dioxide (TiO2) is widely used as ingredient in several products in the nanoform. TiO2-nanoparticles (NPs) are also currently studied for different medical applications. A large debate exists on possible adverse health effects related to their exposure. While there is some evidence of TiO2-NP central nervous system toxicity, their effects on peripheral neurons have been poorly explored. In this study we investigated the effects of TiO2-NPs on dorsal root ganglion (DRG) sensory neurons and satellite glial cells that may be reached by nanoparticles from the bloodstream. We found that TiO2-NPs are internalized in DRG cells and induce apoptosis in a dose dependent manner in both types of cells, ROS production and changes in expression of proinflammatory cytokine IL-1ß. Furthermore, we found that the axonal retrograde transport is altered in neurons upon exposure to TiO2-NPs. Overall, the results indicate a potential neurotoxic effect of TiO2-NPs on DRG cells. FROM THE CLINICAL EDITOR: Exposure to titanium dioxide nanoparticles is increasing in medical practice. Little is known about their potential toxic effects on the peripheral nervous system. The authors studied this aspect and showed that titanium nanoparticles might potentially cause toxicity over long term.
Assuntos
Apoptose/efeitos dos fármacos , Gânglios Espinais/metabolismo , Nanopartículas Metálicas , Titânio/metabolismo , Animais , Embrião de Galinha , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Interleucina-1beta/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Titânio/farmacologiaRESUMO
High-aspect-ratio nanomaterials (HARN) (typically, single-walled carbon nanotubes (SWCNT) or multiwalled carbon nanotubes (MWCNT)) impair airway barrier function and are toxic to macrophages. Here, we assess the biological effects of nanotubes of imogolite (INT), a hydrated alumino-silicate [(OH)3Al2O3SiOH] occurring as single-walled NT, on murine macrophages and human airway epithelial cells. Cell viability was assessed with resazurin. RT-PCR was used to study the expression of Nos2 and Arg1, markers of classical or alternative macrophage activation, respectively, and nitrite concentration in the medium was determined to assess NO production. Epithelial barrier integrity was evaluated from the trans-epithelial electrical resistance (TEER). Potential genotoxicity of INT was assessed with comet and cytokinesis-block micronucleus cytome assays. Compared to MWCNT and SWCNT, INT caused much smaller effects on RAW264.7 and MH-S macrophage viability. The incubation of macrophages with INT at doses as high as 120 µg/cm(2) for 72 h did not alter either Nos2 or Arg1 expression nor did it increase NO production, whereas IL6 was induced in RAW264.7 cells but not in MH-S cells. INT did not show any genotoxic effect in RAW264.7 and A549 cells except for a decrease in DNA integrity observed in epithelial A549 cells after treatment with the highest dose (80 µg/cm(2)). No significant change in permeability was recorded in Calu-3 epithelial cell monolayers exposed to INT, whereas comparable doses of both SWCNT and MWCNT lowered TEER. Thus, in spite of their fibrous nature, INT appear not to be markedly toxic for in vitro models of lung-blood barrier cells.
Assuntos
Silicatos de Alumínio/toxicidade , Nanotubos/toxicidade , Silicatos de Alumínio/química , Animais , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Formiatos/química , Radicais Livres/química , Humanos , Peróxido de Hidrogênio/química , Camundongos , Testes para Micronúcleos , Nanotubos/química , Nanotubos de Carbono/toxicidade , Óxido Nítrico/metabolismoRESUMO
BACKGROUND: The hemolytic activity of inhaled particles such as silica has been widely investigated in the past and represents a usual toxicological endpoint to characterize particle reactivity despite the fact that red blood cells (RBCs) are not involved in the pathogenesis of pulmonary inflammation or fibrosis caused by some inhaled particles. The inflammatory process induced by silica starts with the activation of the inflammasome, which leads to the release of mature IL-1ß. One of the upstream mechanisms causing activation of the inflammasome is the labilization of the phagolysosomal membrane after particle phagocytosis. Considering RBC lysis as a model of membrane damage, we evaluated the relationship between hemolytic activity and inflammasome-dependent release of IL-1ß for a panel of selected silica particles, in search of the toxicological significance of the hemolytic activity of an inhaled particle. METHODS: Well-characterized silica particles, including four quartz samples and a vitreous silica, with different surface properties and hemolytic potential were tested for their capacity to induce inflammasome-dependent release of IL-1ß in LPS-primed primary murine peritoneal macrophages by ELISA and Western blot analysis. The mechanisms of IL-1ß maturation and release were clarified by using ASC-deficient cells and inhibitors of phagocytosis and cathepsin B. RESULTS: The silica samples induced dose-dependent hemolysis and IL-1ß release of different amplitudes. A significant correlation between IL-1ß release and hemolytic activity was evidenced (r = 0.827) by linear regression analysis. IL-1ß release was completely abolished in ASC-deficient cells and reduced by inhibitors, confirming the involvement of the inflammasome and the requirement of phagocytosis and cathepsin B for activation. CONCLUSIONS: The same physico-chemical properties of silica particles which are relevant for the lysis of the RBC membrane also appear implicated in the labilization of the phagolysosome, leading to inflammasome activation and release of the pro-inflammatory cytokine IL-1ß. These findings strengthen the relevance of the hemolysis assay to predict the pro-inflammatory activity of silica dusts.
Assuntos
Poluentes Atmosféricos/toxicidade , Proteínas Reguladoras de Apoptose/metabolismo , Hemolíticos/toxicidade , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Modelos Biológicos , Dióxido de Silício/toxicidade , Poluentes Atmosféricos/química , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Adaptadoras de Sinalização CARD , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fenômenos Químicos , Hemolíticos/química , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Tamanho da Partícula , Quartzo/química , Quartzo/toxicidade , Dióxido de Silício/química , Propriedades de SuperfícieRESUMO
Boehmite (γ-AlOOH) nanoparticles (NPs) are used in a wide range of industrial applications. However, little is known about their potential toxicity. This study aimed at a better understanding of the relationship between the physico-chemical properties of these NPs and their in vitro biological activity. After an extensive physico-chemical characterization, the cytotoxicity, pro-inflammatory response and oxidative stress induced by a bulk industrial powder and its ultrafine fraction were assessed using RAW264.7 macrophages. Although the bulk powder did not trigger a significant biological activity, pro-inflammatory response was highly enhanced with the ultrafine fraction. This observation was confirmed with boehmite NPs synthesized at the laboratory scale, with well-defined and tightly controlled physico-chemical features: toxicity was increased when NPs were dispersed. In conclusion, the agglomerates size of boehmite NPs has a major impact on their toxicity, highlighting the need to study not only raw industrial powders containing NPs but also the ultrafine fractions representative of respirable particles.
Assuntos
Hidróxido de Alumínio/toxicidade , Óxido de Alumínio/toxicidade , Macrófagos/efeitos dos fármacos , Nanopartículas/química , Hidróxido de Alumínio/química , Óxido de Alumínio/química , Animais , Linhagem Celular , Fenômenos Químicos , Inflamação , Macrófagos/citologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Testes de ToxicidadeRESUMO
Sugarcane combustion generates fine-grained particulate that has the potential to be a respiratory health hazard because of its grain size and composition. In particular, conversion of amorphous silica to crystalline forms during burning may provide a source of toxic particles. In this study, we investigate and evaluate the toxicity of sugarcane ash and bagasse ash formed from commercial sugarcane burning. Experiments to determine the main physicochemical properties of the particles, known to modulate biological responses, were combined with cellular toxicity assays to gain insight into the potential reactions that could occur at the particle-lung interface following inhalation. The specific surface area of the particles ranged from â¼16 to 90 m(2) g(-1) . The samples did not generate hydroxyl- or carbon-centered radicals in cell-free tests. However, all samples were able to 'scavenge' an external source of hydroxyl radicals, which may be indicative of defects on the particle surfaces that may interfere with cellular processes. The bioavailable iron on the particle surfaces was low (2-3 µmol m(-2) ), indicating a low propensity for iron-catalyzed radical generation. The sample surfaces were all hydrophilic and slightly acidic, which may be due to the presence of oxygenated (functional) groups. The ability to cause oxidative stress and membrane rupture in red blood cells (hemolysis) was found to be low, indicating that the samples are not toxic by the mechanisms tested. Cytotoxicity of sugarcane ash was observed, by measuring lactate dehydrogenase release, after incubation of relatively high concentrations of ash with murine alveolar macrophage cells. All samples induced nitrogen oxide release (although only at very high concentrations) and reactive oxygen species generation (although the bagasse samples were less potent than the sugarcane ash). However, the samples induced significantly lower cytotoxic effects and nitrogen oxide generation when compared with the positive control.
Assuntos
Celulose/toxicidade , Eritrócitos/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Saccharum/toxicidade , Dióxido de Silício/toxicidade , Animais , Carbono/química , Células Cultivadas , Cristalização , Incêndios , Radical Hidroxila/química , Ferro/química , Camundongos , Estresse Oxidativo , Tamanho da PartículaRESUMO
Nanometric TiO2 is largely employed in cosmetics, but in vitro toxic effects have been reported when nano-TiO2 is exposed to UV light. The photoreactivity of TiO2 largely depends on its crystal phase, namely, anatase and rutile. Surface acidity, which is also dependent on crystal structure, may impart a positive or negative charge to the nanomaterial surface and ultimately modulate particle adhesion to tissues. Three nanometric TiO2 powders with a different crystal lattice and surface charge (anatase, rutile, and anatase/rutile) have been employed here to investigate their interaction with the skin and to examine the molecular mechanisms of the TiO2-induced oxidative damage. The strength of the interaction of nano-TiO2 with skin has been revealed by chemiometric mapping (µ-XRF and SEM-EDS) after tissue washing. Positively charged anatase and anatase/rutile, but not negatively charged rutile, were strongly held on the skin surface and were able to promote a structural rearrangement of the lipid bilayer in the stratum corneum (DSC and Raman) under controlled indoor illumination (UVA < 1 mW/m²). Under the same conditions, cell-free reactivity tests (ROS-mediated free-radical release and lipoperoxidation) indicated that anatase and anatase/rutile are more reactive than rutile, suggesting a ROS-mediated oxidative mechanism that may alter the structure of the stratum corneum. Both the higher oxidative potential and the stronger adhesion to skin of anatase and anatase/rutile TiO2 may explain the stronger disorganization induced by these two samples and suggests the use of rutile to produce safer TiO2-based cosmetic and pharmaceutical products.
Assuntos
Epiderme/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Titânio/química , Raios Ultravioleta , Animais , Varredura Diferencial de Calorimetria , Cristalização , Epiderme/efeitos da radiação , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Nanopartículas Metálicas/química , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Análise Espectral Raman , Propriedades de Superfície , SuínosRESUMO
To evaluate the effect of carbonaceous materials on the pathogenic activity of quartz dusts, mixtures of carbon soot (1 and 10%) and quartz (Min-U-Sil) were prepared and then milled so to attain an intimate association of carbon and the quartz surface. Both cellular and cell-free tests show that carbon associated to quartz completely inhibits the typical free radical generation of quartz dusts (through Fenton activity and homolytic cleavage of a C-H bond) and suppresses the oxidative stress and inflammation induced by quartz alone on MH-S murine macrophage cells (lipid peroxidation, nitric oxide release, and tumor necrosis factor-α synthesis). The cytotoxic response to quartz is also largely reduced. An extremely pure quartz milled with 10% of soot showed inactivating effects on the adverse reactions to quartz similar to Min-U-Sil quartz. None of these effects takes place when the same experiments are carried out with mechanically mixed samples, which suggests that carbon acts not just as a radical quencher but because of its association to the quartz surface.
Assuntos
Carbono/química , Poeira/análise , Quartzo/química , Dióxido de Silício/química , Animais , Linhagem Celular , Radical Hidroxila/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Quartzo/toxicidade , Dióxido de Silício/toxicidade , Propriedades de Superfície , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The membranolytic activity of silica particles toward red blood cells (RBCs) has been known for a long time and is sometimes associated with silica pathogenicity. However, the molecular mechanism and the reasons why hemolysis differs according to the silica form are still obscure. A panel of 15 crystalline (pure and commercial) and amorphous (pyrogenic, precipitated from aqueous solutions, vitreous) silica samples differing in size, origin, morphology, and surface chemical composition were selected and specifically prepared. Silica particles were grouped into six groups to compare their potential in disrupting RBC membranes so that one single property differed in each group, while other features were constant. Free radical production and crystallinity were not strict determinants of hemolytic activity. Particle curvature and morphology modulated the hemolytic effect, but silanols and siloxane bridges at the surface were the main actors. Hemolysis was unrelated to the overall concentration of silanols as fully rehydrated surfaces (such as those obtained from aqueous solution) were inert, and one pyrogenic silica also lost its membranolytic potential upon progressive dehydration. Overall results are consistent with a model whereby hemolysis is determined by a defined surface distribution of dissociated/undissociated silanols and siloxane groups strongly interacting with specific epitopes on the RBC membrane.
Assuntos
Eritrócitos/efeitos dos fármacos , Dióxido de Silício/toxicidade , Alumínio/química , Cristalização , Eritrócitos/metabolismo , Radicais Livres/metabolismo , Hemólise , Temperatura Alta , Humanos , Íons/química , Tamanho da Partícula , Dióxido de Silício/química , Propriedades de SuperfícieRESUMO
Malignant mesothelioma is closely connected to asbestos exposure, with epidemiological patterns closely reshaping the geography and history of asbestos exposure. Mechanisms of causation and of interaction of asbestos fibres with pleura are complex and currently not yet completely understood. Curative efforts so far provided little results. Italy shows one of the highest incidence of MM and developed a network of specialized cancer registries in order to monitor disease occurrence and describe its epidemiology in details. The second Italian Consensus Conference on Pleural Mesothelioma convened in Torino on November 24th-25th, 2011. Besides the main consensus report summarizing the contribution of the different expertises, that was published elsewhere, the participants in 'Public Health and Epidemiology' section decided to report in major details the evidence and the conclusions regarding epidemiology, causative mechanisms and the public health impact of the disease.
Assuntos
Mesotelioma/epidemiologia , Neoplasias Pleurais/epidemiologia , Saúde Pública , Humanos , Itália/epidemiologia , Mesotelioma/etiologia , Neoplasias Pleurais/etiologiaRESUMO
Two samples of highly pure multiwalled carbon nanotubes (MWCNTs) similar in hydrophobicity and surface reactivity were prepared with similar length, <5 µm, but markedly different diameter (9.4 vs 70 nm). The samples were compared for their cytotoxic activity, uptake, and ability to induce oxidative stress (ROS production and intracellular GSH depletion) in vitro in murine alveolar macrophages (MH-S). The in vivo toxicity was evaluated by measuring biochemical (LDH activity and total proteins) and cellular responses in bronchoalveolar lavage (BAL) after intratracheal instillation in rats. Both samples were internalized in MH-S cells. However, thin MWCNTs appeared significantly more toxic than the thicker ones, both in vitro and in vivo, when compared on a mass-dose basis. The data reported herein suggest that the nanotube diameter is an important parameter to be considered in the toxicological assessment of CNTs.
Assuntos
Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Nanotubos de Carbono/química , Nanotubos de Carbono/toxicidade , Animais , Transporte Biológico , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Feminino , Glutationa/metabolismo , L-Lactato Desidrogenase/metabolismo , Pulmão/metabolismo , Macrófagos Alveolares/metabolismo , Camundongos , Microscopia Eletrônica de Transmissão , Nanotubos de Carbono/ultraestrutura , Tamanho da Partícula , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Análise Espectral Raman , Propriedades de SuperfícieRESUMO
Three hematite samples were synthesized by precipitation from a FeCl3 solution under controlled pH and temperature conditions in different morphology and dimensions: (i) microsized (average diameter 1.2 µm); (ii) submicrosized (250 nm); and (iii) nanosized (90 nm). To gain insight into reactions potentially occurring in vivo at the particle-lung interface following dust inhalation, several physicochemical features relevant to pathogenicity were measured (free radical generation in cell-free tests, metal release, and antioxidant depletion), and cellular toxicity assays on human lung epithelial cells (A549) and murine alveolar macrophages (MH-S) were carried out (LDH release, apoptosis detection, DNA damage, and nitric oxide synthesis). The decrease in particles size, from 1.2 µm to 90 nm, only caused a slight increase in structural defects (disorder of the hematite phase and the presence of surface ferrous ions) without enhancing surface reactivity or cellular responses in the concentration range between 20 and 100 µg cm⻲.
Assuntos
Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Compostos Férricos/toxicidade , L-Lactato Desidrogenase/metabolismo , Macrófagos Alveolares/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Óxido Nítrico/metabolismo , Animais , Linhagem Celular , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Células Epiteliais/metabolismo , Compostos Férricos/química , Humanos , Concentração de Íons de Hidrogênio , Macrófagos Alveolares/citologia , Macrófagos Alveolares/metabolismo , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Camundongos , Tamanho da Partícula , TemperaturaRESUMO
High aspect-ratio nanomaterials (HARNs) have recently attracted great attention from nanotoxicologists because of their similarity to asbestos. However, the actual risk associated with the exposure to nanosized asbestos, which escapes most regulations worldwide, is still unknown. Nanometric fibers of chrysotile asbestos have been prepared from two natural sources to investigate whether nanosize may modulate asbestos toxicity and gain insight on the hazard posed by naturally occurring asbestos, which may be defined as HARNs because of their dimensions. Power ultrasound was used to obtain nanofibers from two different chrysotile specimens, one from the dismissed asbestos mine in Balangero (Italian Western Alps) and the other from a serpentine outcrop in the Italian Central Alps. Electron microscopy, X-ray diffraction, and fluorescence spectroscopy revealed that the procedure does not affect mineralogical and chemical composition. Surface reactions related to oxidative stress, free radical generation, bioavailability of iron, and antioxidant depletion, revealed a consistent reduction in reactivity upon reduction in size. When tested on A549 human epithelial cells, the pristine but not the nanosized fibers proved cytotoxic (LDH release), induced NO production, and caused lipid peroxidation. However, nanofibers still induced some toxicity relevant oxidative stress activity (ROS production) in a dose-dependent fashion. The reduction in length and a lack of poorly coordinated bioavailable iron in nanochrysotile may explain this behavior. The present study provides a one-step procedure for the preparation of a homogeneous batch of natural asbestos nanofibers and shows how a well-known toxic material might not necessarily become more toxic than its micrometric counterpart when reduced to the nanoscale.