RESUMEN
PURPOSE: To investigate the in vitro biocompatibility of human gingival fibroblasts with preformed paediatric crowns and resistance to acid exposure at levels that simulate the oral environment. METHODS: This laboratory study investigated primary HGFs viability, metabolic activity, cytotoxicity, and apoptotic events on preformed metal crown discs, composite resin-coated wells, and monolithic zirconia fragments at 24, 48, and 72 h using the ApoTox-Glo Triplex assay. The PPCs were also immersed in 0.1% lactic acid, 0.2% phosphoric acid, or 10% citric acid for 7 days at 37 °C to reproduce conditions associated with dietary intake or gastric reflux. Samples were then subject to inductively coupled plasma optical emission spectrometry to quantitate the release of ions. RESULTS: The viability of HGFs on stainless steel and CR significantly declined at 48 and 72 h, representing potential cytotoxicity (p < 0.05). Cytotoxicity of HGFs was also higher for stainless steel and ZR compared to control (p < 0.05). PMCs and ZR crowns gave minimal ion release. Meanwhile, significant quantities of metallic ions, including copper (Cu), iron (Fe), nickel (Ni), and zinc (Zn), were present in eluates from veneered-preformed metal crowns. CONCLUSION: As PPCs can be exposed to highly acidic environments for many years, thus the release of metallic ions from V-PMCs should form the further investigation in future studies.
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Materiales Biocompatibles , Coronas , Fibroblastos , Encía , Ensayo de Materiales , Acero Inoxidable , Circonio , Humanos , Fibroblastos/efectos de los fármacos , Acero Inoxidable/química , Acero Inoxidable/toxicidad , Encía/efectos de los fármacos , Encía/citología , Resinas Compuestas/toxicidad , Resinas Compuestas/química , Supervivencia Celular/efectos de los fármacos , Niño , Zinc , Ácido Cítrico , Técnicas In Vitro , Níquel , Cobre , Ácidos Fosfóricos , Ácido Láctico , Cromo/toxicidad , Materiales Dentales/toxicidad , Aleaciones Dentales/toxicidad , Aleaciones Dentales/química , Ácidos , HierroRESUMEN
Telomeres are inert DNA sequences (TTAGGG) at the end of chromosomes that protect genetic information and maintain DNA integrity. Emerging evidence has demonstrated that telomere alteration can be closely related to occupational exposure and the development of various disease conditions, including cancer. However, the functions and underlying molecular mechanisms of telomere alteration and shelterin dysregulation after welding fume exposures have not been broadly defined. In this study, we analyzed telomere length and shelterin complex proteins in peripheral blood mononuclear cells (PBMCs) and in lung tissue recovered from male Sprague-Dawley rats following exposure by intratracheal instillation (ITI) to 2 mg/rat of manual metal arc-stainless steel (MMA-SS) welding fume particulate or saline (vehicle control). PBMCs and lung tissue were harvested at 30 d after instillation. Our study identified telomere elongation and shelterin dysregulation in PBMCs and lung tissue after welding fume exposure. Mechanistically, telomere elongation was independent of telomerase reverse transcriptase (TERT) activation. Collectively, our findings demonstrated that welding fume-induced telomere elongation was (a) TERT-independent and (b) associated with shelterin complex dysregulation. It is possible that an alteration of telomere length and its regulatory proteins may be utilized as predictive biomarkers for various disease conditions after welding fume exposure. This needs further investigation.
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Pulmón , Ratas Sprague-Dawley , Acero Inoxidable , Telomerasa , Soldadura , Animales , Masculino , Ratas , Contaminantes Ocupacionales del Aire/toxicidad , Exposición por Inhalación/efectos adversos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Acero Inoxidable/toxicidad , Telomerasa/genética , Telomerasa/metabolismo , Telómero/efectos de los fármacos , Proteínas de Unión a Telómeros/genética , Proteínas de Unión a Telómeros/metabolismoRESUMEN
The comet assay was recently applied for the first time to test the genotoxicity of micrometric stainless steel and cement particles, representative of those produced in the dismantling of nuclear power plants. A large dataset was obtained from in vitro exposure of BEAS-2B lung cells to different concentrations of hydrogenated (non-radiative control) and tritiated particles, to assess the impact of accidental inhalation. Starting from the distributions of the number of nuclei scored at different extent of DNA damage (% tail DNA values), we propose a new comet data treatment designed to consider the inhomogeneity of the action of such particles. Indeed, due to particle behavior in biological media and concentration, a large fraction of cells remains undamaged, and standard averaging of genotoxicity indicators leads to a misinterpretation of experimental results. The analysis we propose reaches the following goals: genotoxicity in human lung cells is assessed for stainless steel and cement microparticles; the role of radiative damage due to tritium is disentangled from particulate stress; the fraction of damaged cells and their average level of DNA damage are assessed separately, which is essential for carcinogenesis implications and sets the basis for a better-informed risk management for human exposure to radioactive particles.
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Acero Inoxidable , Acero , Humanos , Ensayo Cometa , Acero/farmacología , Acero Inoxidable/toxicidad , Daño del ADN , PulmónRESUMEN
During the decommissioning of nuclear facilities, the tritiated materials must be removed. These operations generate tritiated steel and cement particles that could be accidentally inhaled by workers. Thus, the consequences of human exposure by inhalation to these particles in terms of radiotoxicology were investigated. Their cyto-genotoxicity was studied using two human lung models: the BEAS-2B cell line and the 3D MucilAirTM model. Exposures of the BEAS-2B cell line to particles (2 and 24 h) did not induce significant cytotoxicity. Nevertheless, DNA damage occurred upon exposure to tritiated and non-tritiated particles, as observed by alkaline comet assay. Tritiated particles only induced cytostasis; however, both induced a significant increase in centromere negative micronuclei. Particles were also assessed for their effects on epithelial integrity and metabolic activity using the MucilAirTM model in a 14-day kinetic mode. No effect was noted. Tritium transfer through the epithelium was observed without intracellular accumulation. Overall, tritiated and non-tritiated stainless steel and cement particles were associated with moderate toxicity. However, these particles induce DNA lesions and chromosome breakage to which tritium seems to contribute. These data should help in a better management of the risk related to the inhalation of these types of particles.
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Daño del ADN , Acero Inoxidable , Ensayo Cometa , Humanos , Pulmón/metabolismo , Acero Inoxidable/toxicidad , Tritio/farmacologíaRESUMEN
Thermal spray coating is an industrial process in which molten metal is sprayed at high velocity onto a surface as a protective coating. An automated electric arc wire thermal spray coating aerosol generator and inhalation exposure system was developed to simulate an occupational exposure and, using this system, male Sprague-Dawley rats were exposed to stainless steel PMET720 aerosols at 25 mg/m3 × 4 h/day × 9 day. Lung injury, inflammation, and cytokine alteration were determined. Resolution was assessed by evaluating these parameters at 1, 7, 14 and 28 d after exposure. The aerosols generated were also collected and characterized. Macrophages were exposed in vitro over a wide dose range (0-200 µg/ml) to determine cytotoxicity and to screen for known mechanisms of toxicity. Welding fumes were used as comparative particulate controls. In vivo lung damage, inflammation and alteration in cytokines were observed 1 day post exposure and this response resolved by day 7. Alveolar macrophages retained the particulates even after 28 day post-exposure. In line with the pulmonary toxicity findings, in vitro cytotoxicity and membrane damage in macrophages were observed only at the higher doses. Electron paramagnetic resonance showed in an acellular environment the particulate generated free radicals and a dose-dependent increase in intracellular oxidative stress and NF-kB/AP-1 activity was observed. PMET720 particles were internalized via clathrin and caveolar mediated endocytosis as well as actin-dependent pinocytosis/phagocytosis. The results suggest that compared to stainless steel welding fumes, the PMET 720 aerosols were not as overtly toxic, and the animals recovered from the acute pulmonary injury by 7 days.
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Contaminantes Ocupacionales del Aire , Soldadura , Ratas , Animales , Masculino , Acero Inoxidable/toxicidad , Contaminantes Ocupacionales del Aire/toxicidad , FN-kappa B , Actinas , Factor de Transcripción AP-1 , Ratas Sprague-Dawley , Aerosoles y Gotitas Respiratorias , Soldadura/métodos , Exposición por Inhalación/efectos adversos , Pulmón , Polvo , Inflamación/patología , Citocinas , Clatrina/farmacologíaRESUMEN
Stainless steels are widely used iron-based alloys that contain chromium and, typically, other alloying elements. The chromium(III)-rich surface oxide of stainless steels efficiently limits the release (bioaccessibility) of their metal constituents in most physiological environments, influencing the toxicity of the alloy. Of the constituents and impurities of stainless steels, nickel and cobalt are of particular interest, primarily due to skin sensitization and repeated-dose inhalation toxicity of nickel, and (inhalation) carcinogenicity of cobalt. A review of the available toxicological data on stainless steels, and the toxicological, mechanistic, and bioaccessibility data on their constituent metals supports the low toxicity and non-carcinogenicity of stainless steels. The comparative metal release, rather than the bulk composition of stainless steels, needs to be considered when assessing their health hazard classification according to the UN Globally Harmonized System, and the corresponding EU CLP regulation. As an illustrative example, a 28-day inhalation toxicity study on stainless steel powder showed no signs of lung toxicity at exposure levels at which significant toxicity would have been expected on the basis of its bulk nickel content. This finding is associated with the low bioaccessibility of nickel from the alloy in the lungs.
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Níquel , Acero Inoxidable , Aleaciones/toxicidad , Cromo/toxicidad , Cobalto , Níquel/toxicidad , Acero Inoxidable/toxicidad , AceroRESUMEN
Additive manufacturing (AM) or "3D-printing" is a ground-breaking technology that enables the production of complex 3D parts. Its rapid growth calls for immediate toxicological investigations of possible human exposures in order to estimate occupational health risks. Several laser-based powder bed fusion AM techniques are available of which many use metal powder in the micrometer range as feedstock. Large energy input from the laser on metal powders generates several by-products, like spatter and condensate particles. Due to often altered physicochemical properties and composition, spatter and condensate particles can result in different toxicological responses compared to the original powder particles. The toxicity of such particles has, however, not yet been investigated. The aim of the present study was to investigate the toxicity of condensate/spatter particles formed and collected upon selective laser melting (SLM) printing of metal alloy powders, including a nickel-chromium-based superalloy (IN939), a nickel-based alloy (Hastelloy X, HX), a high-strength maraging steel (18Ni300), a stainless steel (316L), and a titanium alloy (Ti6Al4V). Toxicological endpoints investigated included cytotoxicity, generation of reactive oxygen species (ROS), genotoxicity (comet and micronucleus formation), and inflammatory response (cytokine/chemokine profiling) following exposure of human bronchial epithelial cells (HBEC) or monocytes/macrophages (THP-1). The results showed no or minor cytotoxicity in the doses tested (10-100 µg/mL). Furthermore, no ROS generation or formation of micronucleus was observed in the HBEC cells. However, an increase in DNA strand breaks (detected by comet assay) was noted in cells exposed to HX, IN939, and Ti6Al4V, whereas no evident release of pro-inflammatory cytokine was observed from macrophages. Particle and surface characterization showed agglomeration in solution and different surface oxide compositions compared to the nominal bulk content. The extent of released nickel was small and related to the nickel content of the surface oxides, which was largely different from the bulk content. This may explain the limited toxicity found despite the high Ni bulk content of several powders. Taken together, this study suggests relatively low acute toxicity of condensates/spatter particles formed during SLM-printing using IN939, HX, 18Ni300, 316L, and Ti6Al4V as original metal powders.
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Aleaciones/toxicidad , Células Epiteliales/efectos de los fármacos , Pulmón/efectos de los fármacos , Macrófagos/efectos de los fármacos , Neumonía/inducido químicamente , Impresión Tridimensional , Aleaciones de Cromo/toxicidad , Citocinas/genética , Citocinas/metabolismo , Daño del ADN , Relación Dosis-Respuesta a Droga , Células Epiteliales/metabolismo , Células Epiteliales/patología , Humanos , Mediadores de Inflamación/metabolismo , Pulmón/metabolismo , Pulmón/patología , Macrófagos/metabolismo , Macrófagos/patología , Pruebas de Mutagenicidad , Estrés Oxidativo/efectos de los fármacos , Neumonía/genética , Neumonía/metabolismo , Neumonía/patología , Polvos , Especies Reactivas de Oxígeno/metabolismo , Medición de Riesgo , Acero Inoxidable/toxicidad , Células THP-1 , Titanio/toxicidadRESUMEN
Welding fumes induce lung toxicity and are carcinogenic to humans but the molecular mechanisms have yet to be clarified. The aim of this study was to evaluate the toxicity of stainless and mild steel particles generated via gas-metal arc welding using primary human small airway epithelial cells (hSAEC) and ToxTracker reporter murine stem cells, which track activation of six cancer-related pathways. Metal content (Fe, Mn, Ni, Cr) of the particles was relatively homogenous across particle size. The particles were not cytotoxic in reporter stem cells but stainless steel particles activated the Nrf2-dependent oxidative stress pathway. In hSAEC, both particle types induced time- and dose-dependent cytotoxicity, and stainless steel particles also increased generation of reactive oxygen species. The cellular metal content was higher for hSAEC compared to the reporter stem cells exposed to the same nominal dose. This was, in part, related to differences in particle agglomeration/sedimentation in the different cell media. Overall, our study showed differences in cytotoxicity and activation of cancer-related pathways between stainless and mild steel welding particles. Moreover, our data emphasizes the need for careful assessment of the cellular dose when comparing studies using different in vitro models.
Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Acero Inoxidable/toxicidad , Acero/toxicidad , Soldadura , Contaminantes Ocupacionales del Aire/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/ultraestructura , Humanos , Exposición por Inhalación/efectos adversos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Ratones , Microscopía Electrónica de Transmisión , Células Madre Embrionarias de Ratones/efectos de los fármacos , Células Madre Embrionarias de Ratones/metabolismo , Células Madre Embrionarias de Ratones/ultraestructura , Tamaño de la Partícula , Especies Reactivas de Oxígeno/metabolismo , Acero Inoxidable/química , Acero/química , Soldadura/métodosRESUMEN
The rationale behind the success of nickel free or with extremely low nickel austenitic high manganese and nitrogen stabilized stainless steels is adverse influences of nickel ion on human body. Replacement of nickel by nitrogen and manganese provides a stable microstructure and facilitates better biocompatibility in respect of the conventional 316L austenitic stainless steel (316L SS). In this investigation, biocompatibility of the high-manganese and nitrogen stabilized (Fe-18Cr-22Mn-0.65N) austenitic stainless steel was studied and found highly promising.In vitrocell culture and cell proliferation (MTT) assays were performed on this stainless steel and assessed in respect of the 316L SS. Both the steels exhibited similar cell growth behavior. Furthermore, an enhancement was observed in cell proliferation on the Fe-18Cr-22Mn-0.65N SS after surface modification by ultrasonic shot peening (USP). The mean percent proliferation of the MG-63 cells increased from ≈88% for Un-USP to 98% and 105% for USP 3-2 and USP 2-2 samples, respectively for 5 d of incubation. Interestingly,in vivoanimal study performed in rabbits for 3 and 6 weeks showed callus formation and sign of union without any allergic reaction.
Asunto(s)
Materiales Biocompatibles , Aleaciones Dentales , Prótesis e Implantes , Acero Inoxidable , Materiales Biocompatibles/química , Materiales Biocompatibles/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Aleaciones Dentales/química , Aleaciones Dentales/toxicidad , Humanos , Manganeso/química , Ensayo de Materiales , Nitrógeno/química , Acero Inoxidable/química , Acero Inoxidable/toxicidadRESUMEN
Welders are daily exposed to various levels of welding fumes containing several metals. This exposure can lead to an increased risk for different health effects which serves as a driving force to develop new methods that generate less toxic fumes. The aim of this study was to explore the role of released metals for welding particle-induced toxicity and to test the hypothesis that a reduction of Cr(VI) in welding fumes results in less toxicity by comparing the welding fume particles of optimized Cr(VI)-reduced flux-cored wires (FCWs) to standard FCWs. The welding particles were thoroughly characterized, and toxicity (cell viability, DNA damage and inflammation) was assessed following exposure to welding particles as well as their released metal fraction using cultured human bronchial epithelial cells (HBEC-3kt, 5-100 µg/mL) and human monocyte-derived macrophages (THP-1, 10-50 µg/mL). The results showed that all Cr was released as Cr(VI) for welding particles generated using standard FCWs whereas only minor levels (< 3% of total Cr) were released from the newly developed FCWs. Furthermore, the new FCWs were considerably less cytotoxic and did not cause any DNA damage in the doses tested. For the standard FCWs, the Cr(VI) released in cell media seemed to explain a large part of the cytotoxicity and DNA damage. In contrast, all particles caused rather similar inflammatory effects suggesting different underlying mechanisms. Taken together, this study suggests a potential benefit of substituting standard FCWs with Cr(VI)-reduced wires to achieve less toxic welding fumes and thus reduced risks for welders.
Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Cromo/toxicidad , Acero Inoxidable/toxicidad , Soldadura , Contaminantes Ocupacionales del Aire/análisis , Bronquios/citología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cromo/análisis , Cromo/química , Daño del ADN/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Humanos , Inflamación/inducido químicamente , Inflamación/patología , Macrófagos/efectos de los fármacos , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Acero Inoxidable/análisis , Células THP-1RESUMEN
Recent evidence has supported welding fume (WF)-derived ultrafine particles (UFP) could be the driving force of their adverse health effects. However, UFP have not yet been extensively studied and are currently not included in present air quality standards/guidelines. Here, attention was focused on the underlying genetic and epigenetic mechanisms by which the quasi-UFP (Q-UFP, i.e., ≤ 0.25 µm) of the WF emitted by gas metal arc welding-stainless steel (GMAW-SS) exert their toxicity in human bronchial epithelial BEAS-2B cells. The Q-UFP under study showed a monomodal size distribution in number centered on 104.4 ± 52.3 nm and a zeta potential of -13.8 ± 0.3 mV. They were enriched in Fe > Cr > Mn > Si, and displayed a relatively high intrinsic oxidative potential. Dose-dependent activation of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B signaling pathway, glutathione alteration, and DNA, protein and lipid oxidative damage were reported in BEAS-2B cells acutely (1.5 and 9 µg/cm2, 24 h) or repeatedly (0.25 and 1.5 µg/cm2, 3 × 24 h) exposed to Q-UFP (p < 0.05). Alterations of the Histone H3 acetylation were reported for any exposure (p < 0.05). Differentially regulated miRNA and mRNA indicated the activation of some critical cell signaling pathways related to oxidative stress, inflammation, and cell cycle deregulation towards apoptosis. Taken together, these results highlighted the urgent need to better evaluate the respective toxicity of the different metals and to include the Q-UFP fraction of WF in current air quality standards/guidelines relevant to the occupational settings.
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Soldadura , Epigénesis Genética , Gases , Humanos , Metales , Material Particulado/toxicidad , Acero Inoxidable/toxicidad , Soldadura/métodosRESUMEN
In 2017, the International Agency for Research on Cancer classified welding fumes as "carcinogenic to humans" (Group 1). Both mild steel (MS) welding, where fumes lack carcinogenic chromium and nickel, and stainless steel (SS) increase lung cancer risk in welders; therefore, further research to better understand the toxicity of the individual metals is needed. The objectives were to (1) compare the pulmonary toxicity of chromium (as Cr(III) oxide [Cr2O3] and Cr (VI) calcium chromate [CaCrO4]), nickel [II] oxide (NiO), iron [III] oxide (Fe2O3), and gas metal arc welding-SS (GMAW-SS) fume; and (2) determine if these metal oxides can promote lung tumors. Lung tumor susceptible A/J mice (male, 4-5 weeks old) were exposed by oropharyngeal aspiration to vehicle, GMAW-SS fume (1.7 mg), or a low or high dose of surrogate metal oxides based on the respective weight percent of each metal in the fume: Cr2O3 + CaCrO4 (366 + 5 µg and 731 + 11 µg), NiO (141 and 281 µg), or Fe2O3 (1 and 2 mg). Bronchoalveolar lavage, histopathology, and lung/liver qPCR were done at 1, 7, 28, and 84 days post-aspiration. In a two-stage lung carcinogenesis model, mice were initiated with 3-methylcholanthrene (10 µg/g; intraperitoneal; 1x) or corn oil then exposed to metal oxides or vehicle (1 x/week for 5 weeks) by oropharyngeal aspiration. Lung tumors were counted at 30 weeks post-initiation. Results indicate the inflammatory potential of the metal oxides was Fe2O3 > Cr2O3 + CaCrO4 > NiO. Overall, the pneumotoxic effects were negligible for NiO, acute but not persistent for Cr2O3 + CaCrO4, and persistent for the Fe2O3 exposures. Fe2O3, but not Cr2O3 + CaCrO4 or NiO significantly promoted lung tumors. These results provide experimental evidence that Fe2O3 is an important mediator of welding fume toxicity and support epidemiological findings and the IARC classification.
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Contaminantes Ocupacionales del Aire/toxicidad , Carcinógenos/toxicidad , Compuestos Férricos/toxicidad , Neoplasias Pulmonares/inducido químicamente , Soldadura/métodos , Animales , Compuestos de Calcio/toxicidad , Carcinogénesis/inducido químicamente , Cromatos/toxicidad , Compuestos de Cromo/toxicidad , Pulmón/efectos de los fármacos , Pulmón/patología , Neoplasias Pulmonares/patología , Masculino , Metilcolantreno/toxicidad , Ratones , Níquel/toxicidad , Acero Inoxidable/química , Acero Inoxidable/toxicidadRESUMEN
OBJECTIVES: Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese, and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. Bronchiolar epithelium Clara cells/club cells, coordinate these inflammatory responses. Clara cells secretory protein (CC16) with ant-inflammatory role. MATERIAL AND METHODS: The pulmonary toxicity of welding dust (WD) was assessed for Wistar rats exposed to 60 mg/m3 of respirable-size welding dust (mean diameter 1.17 µm for 1 and 2 weeks (6 h/day, 5 days/week)) or the aerosols of soluble form (SWD) in the nose-only exposure chambers. Additionally the effect of antiinflammatory betaine supplementation was assessed. Clara cells secretory protein, differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase - LDH) activities were determined in bronchoalveolar lavage fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) and prolactin concentrations were assessed in serum. Histopathology examination of lung, brain, liver, kidney, spleen was done. Additionally slices of brain and lung were exanimated in laser ablation inductively coupled plasma mass spectrometry. RESULTS: Both WD and SWD exposure evoked large bronchiolar infiltration shoved in histopathology examination. In this study, TBARS inversely correlated with a significant decrease of CC16 concentration that occurred after instillation of both WD and SWD indicating decreased anti- inflammatory potential in the lung. In WD exposed rats prolactin correlated with nuclear factor-kappa B (NF-κB), LDH, TBARS and serum levels Cr, Ni and inversely with c-Jun. In SWD exposed rats prolactin correlated with CC16 indicated effect of prolactin on the population of epithelial cells. CONCLUSIONS: In the current study, deleterious effects of repeated inhalation stainless steel welding dust form on club (Clara) cell secretory protein (CC16) were demonstrated. Clara cells secretory protein relation with prolactin in exposed rats to welding dust were shown and explored whether the NF-κB and c-Jun/activator protein 1 related pathway was involved. Int J Occup Med Environ Health 2018;31(5):613-632.
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Polvo , Células Epiteliales/efectos de los fármacos , Acero Inoxidable/toxicidad , Soldadura , Animales , Antiinflamatorios/farmacología , Betaína/farmacología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Corticosterona/sangre , Células Epiteliales/enzimología , Células Epiteliales/metabolismo , Exposición por Inhalación/efectos adversos , L-Lactato Deshidrogenasa/metabolismo , Masculino , FN-kappa B/metabolismo , Prolactina/sangre , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Factor de Transcripción AP-1/metabolismoRESUMEN
Welding fume inhalation causes pulmonary toxicity, including susceptibility to infection. We hypothesized that airway epithelial ion transport is a target of fume toxicity, and investigated the effects of fume particulates from manual metal arc-stainless steel (MMA-SS) and gas metal arc-mild steel (GMA-MS) on ion transport in normal human bronchial epithelium (NHBE) cultured in air-interface. MMA-SS particles, more soluble than GMA-MS particles, contain Cr, Ni, Fe and Mn; GMA-MS particles contain Fe and Mn. MMA-SS or GMA-MS particles (0.0167-166.7µg/cm2) were applied apically to NHBEs. After 18h transepithelial potential difference (Vt), resistance (Rt), and short circuit current (Isc) were measured. Particle effects on Na+ and Cl¯ channels and the Na+,K+,2Cl¯-cotransporter were evaluated using amiloride (apical), 5-nitro-2-[(3-phenylpropyl)amino]benzoic acid (NPPB, apical), and bumetanide (basolateral), respectively. MMA-SS (0.0167-16.7µg/cm2) increased basal Vt. Only 16.7µg/cm2 GMA-MS increased basal Vt significantly. MMA-SS or GMA-MS exposure potentiated Isc responses (decreases) to amiloride and bumetanide, while not affecting those to NPPB, GMA-MS to a lesser degree than MMA-SS. Variable effects on Rt were observed in response to amiloride, and bumetanide. Generally, MMA-SS was more potent in altering responses to amiloride and bumetanide than GMA-MS. Hyperpolarization occurred in the absence of LDH release, but decreases in Vt, Rt, and Isc at higher fume particulate doses accompanied LDH release, to a greater extent for MMA-SS. Thus, Na+ transport and Na+,K+,2Cl¯-cotransport are affected by fume exposure; MMA-MS is more potent than GMA-MS. Enhanced Na+ absorption and decreased airway surface liquid could compromise defenses against infection.
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Contaminantes Ocupacionales del Aire/toxicidad , Bronquios/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Agonistas del Canal de Sodio Epitelial/toxicidad , Canales Epiteliales de Sodio/efectos de los fármacos , Simportadores de Cloruro de Sodio-Potasio/efectos de los fármacos , Acero/toxicidad , Soldadura , Bronquios/metabolismo , Bronquios/patología , Células Cultivadas , Canales de Cloruro/efectos de los fármacos , Canales de Cloruro/metabolismo , Relación Dosis-Respuesta a Droga , Impedancia Eléctrica , Células Epiteliales/metabolismo , Células Epiteliales/patología , Canales Epiteliales de Sodio/metabolismo , Gases , Humanos , Exposición por Inhalación/efectos adversos , Transporte Iónico/efectos de los fármacos , L-Lactato Deshidrogenasa/metabolismo , Potenciales de la Membrana , Exposición Profesional/efectos adversos , Simportadores de Cloruro de Sodio-Potasio/metabolismo , Acero Inoxidable/toxicidad , Factores de TiempoRESUMEN
A persistent theme in biomaterials research comprises of surface engineering and modification of bare metallic substrates for improved cellular response and biocompatibility. Graphene Oxide (GO), a derivative of graphene, has outstanding chemical and mechanical properties; its large surface to volume ratio, ease of surface modification and processing make GO an attractive coating material. GO-coatings have been extensively studied as biosensors. Further owing to its surface nano-architecture, GO-coated surfaces promote cell adhesion and growth, making it suitable for tissue engineering applications. The need to improve the long-term durability and therapeutic effectiveness of commercially available bare 316L stainless steel (SS) surfaces led us to adopt a polymer-free approach which is cost-effective and scalable. GO was immobilized on to 316L SS utilizing amide linkage, to generate a strongly adherent uniform coating with surface roughness. GO-coated 316L SS surfaces showed increased hydrophilicity and biocompatibility with SHSY-5Y neuronal cells, which proliferated well and showed decreased reactive oxygen species (ROS) expression. In contrast, cells did not adhere to bare uncoated 316L SS meshes nor maintain viability when cultured in the vicinity of bare meshes. Therefore the combination of the improved surface properties and biocompatibility implies that GO-coating can be utilized to overcome pertinent limitations of bare metallic 316L SS implant surfaces, especially SS neural electrodes. Also, the procedure for making GO-based protective coatings can be applied to numerous other implants where the development of such protective films is necessary.
Asunto(s)
Materiales Biocompatibles Revestidos/farmacología , Grafito/farmacología , Hierro/toxicidad , Neurotoxinas/toxicidad , Acero Inoxidable/toxicidad , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/química , Módulo de Elasticidad/efectos de los fármacos , Grafito/química , Dureza , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Hierro/química , Ensayo de Materiales , Propilaminas/química , Reproducibilidad de los Resultados , Silanos/química , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie , Difracción de Rayos XRESUMEN
Epidemiologic studies suggest an increased risk of lung cancer with exposure to welding fumes, but controlled animal studies are needed to support this association. Oropharyngeal aspiration of collected "aged" gas metal arc-stainless steel (GMA-SS) welding fume has been shown by our laboratory to promote lung tumor formation in vivo using a two-stage initiation-promotion model. Our objective in this study was to determine whether inhalation of freshly generated GMA-SS welding fume also acts as a lung tumor promoter in lung tumor-susceptible mice. Male A/J mice received intraperitoneal (IP) injections of corn oil or the chemical initiator 3-methylcholanthrene (MCA; 10 µg/g) and 1 week later were exposed by whole-body inhalation to air or GMA-SS welding aerosols for 4 h/d × 4 d/w × 9 w at a target concentration of 40 mg/m3. Lung nodules were enumerated at 30 weeks post-initiation. GMA-SS fume significantly promoted lung tumor multiplicity in A/J mice initiated with MCA (16.11 ± 1.18) compared to MCA/air-exposed mice (7.93 ± 0.82). Histopathological analysis found that the increased number of lung nodules in the MCA/GMA-SS group were hyperplasias and adenomas, which was consistent with developing lung tumorigenesis. Metal deposition analysis in the lung revealed a lower deposited dose, approximately fivefold compared to our previous aspiration study, still elicited a significant lung tumorigenic response. In conclusion, this study demonstrates that inhaling GMA-SS welding fume promotes lung tumorigenesis in vivo which is consistent with the epidemiologic studies that show welders may be at an increased risk for lung cancer.
Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Exposición por Inhalación/efectos adversos , Neoplasias Pulmonares/inducido químicamente , Soldadura , Administración por Inhalación , Animales , Modelos Animales de Enfermedad , Neoplasias Pulmonares/patología , Masculino , Metilcolantreno/administración & dosificación , Ratones , Ratones Endogámicos , Enfermedades Profesionales/etiología , Enfermedades Profesionales/patología , Exposición Profesional/efectos adversos , Acero Inoxidable/toxicidadRESUMEN
Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese (Mn), and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. The principal objective of this study was to determine the dynamics of toxic effects of inhalation exposure to morphologically rated welding dust from stainless steel welding and its soluble form in TSE System with a dynamic airflow. We assessed the pulmonary toxicity of welding dust in Wistar rats exposed to 60.0 mg/m3 of respirable-size welding dust (mean diameter 1.17 µm) for 2 weeks (6 h/day, 5 days/week); the aerosols were generated in the nose-only exposure chambers (NOEC). An additional aim included the study of the effect of betaine supplementation on oxidative deterioration in rat lung during 2 weeks of exposure to welding dust or water-soluble dust form. The animals were divided into eight groups (n = 8 per group): control, dust, betaine, betaine + dust, soluble-form dust, soluble-form dust + betaine, saline and saline + betaine groups. Rats were euthanized 1 or 2 weeks after the last exposure for assessment of pulmonary toxicity. Differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase-LDH) activities were determined in bronchoalveolar lavage (BAL) fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) concentrations were assessed in serum. The increase in polymorphonuclear (PMN) leukocytes in BAL fluid (a cytological index of inflammatory responses of the lung) is believed to reflect pulmonary toxicity of heavy metals. Biomarkers of toxicity assessed in bronchoalveolar fluids indicate that the level of the toxic effect depends mainly on the solubility of studied metal compounds; biomarkers that showed treatment effects included: total cell, neutrophil and lymphocyte counts, total protein concentrations, and cellular enzyme (lactate dehydrogenase) activity. Betaine supplementation at 250 mg/kg/day in all study rats groups attenuated stress indices, and corticosterone and TBARS serum levels, and simultaneously stimulated increase of polymorphonuclear cells in BALF of rats. The study confirmed deleterious effect of transitory metals and particles during experimental inhalation exposure to welding dusts, evidenced in the lungs and brain by increased levels of total protein, higher cellular influx, rise of LDH in BALF, elevated TBARS and increased corticosterone in serum of rats. Our result confirm also the hypothesis about the effect of the welding dusts on the oxidative stress responsible for disturbed systemic homeostasis and impairment of calcium regulation.
Asunto(s)
Contaminantes Ocupacionales del Aire/efectos adversos , Exposición por Inhalación , Acero Inoxidable/toxicidad , Soldadura , Animales , Líquido del Lavado Bronquioalveolar/química , Modelos Animales de Enfermedad , Polvo , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/patología , Masculino , Ratas , Ratas WistarRESUMEN
The present study investigated the antibacterial performance, corrosion resistance and surface properties of antibacterial austenitic 317L-Cu stainless steel (317L-Cu SS). After 4.5wt% copper was added to 317L stainless steel (317L SS), the new alloy underwent solid solution and aging heat treatment. Fluorescent staining using 4',6-diamidino-2-phenylindole (DAPI) revealed that the 317L-Cu SS showed strong antibacterial efficacy, achieving a 99% inhibition rate of sessile Staphylococcus aureus cells after 5days. The corrosion data obtained by potentiodynamic polarization curves indicated that in comparison with 317L SS, the pitting potential and corrosion current density of 317L-Cu slightly decreased due to the addition of Cu. The 317L-Cu SS exhibited no cytotoxicity against zebrafish (Danio rerio) embryos. The experimental results in this study demonstrated that the new alloy has potential applications in medical and daily uses.
Asunto(s)
Biopelículas/efectos de los fármacos , Cobre/farmacología , Acero Inoxidable/farmacología , Staphylococcus aureus/efectos de los fármacos , Animales , Muerte Celular/efectos de los fármacos , Corrosión , Embrión no Mamífero/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Espectroscopía de Fotoelectrones , Polisacáridos Bacterianos/farmacología , Espectrometría por Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , Acero Inoxidable/toxicidad , Propiedades de Superficie , Pruebas de Toxicidad , Pez Cebra/embriologíaRESUMEN
The European chemical framework REACH requires that hazards and risks posed by chemicals, including alloys and metals, are identified and proven safe for humans and the environment. Therefore, differences in bioaccessibility in terms of released metals in synthetic biological fluids (different pH (1.5-7.4) and composition) that are relevant for different human exposure routes (inhalation, ingestion, and dermal contact) have been assessed for powder particles of an alloy containing high levels of nickel (Inconel 718, 57 wt% nickel). This powder is compared with the bioaccessibility of two nickel-containing stainless steel powders (AISI 316L, 10-12% nickel) and with powders representing their main pure alloy constituents: two nickel metal powders (100% nickel), two iron metal powders and two chromium metal powders. X-ray photoelectron spectroscopy, microscopy, light scattering, and nitrogen absorption were employed for the particle and surface oxide characterization. Atomic absorption spectroscopy was used to quantify released amounts of metals in solution. Cytotoxicity (Alamar blue assay) and DNA damage (comet assay) of the Inconel powder were assessed following exposure of the human lung cell line A549, as well as its ability to generate reactive oxygen species (DCFH-DA assay). Despite its high nickel content, the Inconel alloy powder did not release any significant amounts of metals and did not induce any toxic response. It is concluded, that this is related to the high surface passivity of the Inconel powder governed by its chromium-rich surface oxide. Read-across from the pure metal constituents is hence not recommended either for this or any other passive alloy.
Asunto(s)
Aleaciones de Cromo/toxicidad , Níquel/toxicidad , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Aleaciones de Cromo/química , Ensayo Cometa , Daño del ADN , Humanos , Concentración de Iones de Hidrógeno , Exposición por Inhalación/efectos adversos , Luz , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Microscopía Electrónica de Rastreo , Níquel/química , Espectroscopía de Fotoelectrones , Polvos , Especies Reactivas de Oxígeno/química , Medición de Riesgo , Dispersión del Ángulo Pequeño , Solubilidad , Espectrofotometría Atómica , Acero Inoxidable/química , Acero Inoxidable/toxicidad , Propiedades de Superficie , Pruebas de Toxicidad/métodosRESUMEN
OBJECTIVE: The effect of orange juice and Coca Cola(®) on the release of metal ions from fixed orthodontic appliances. MATERIALS AND METHODS: A continuous flow system designed for in vitro testing of orthodontic appliances was used. Orange juice/Coca Cola(®) was flowing through the system alternately with artificial saliva for 5.5 and 18.5h, respectively. The collected samples underwent a multielemental ICP-OES analysis in order to determine the metal ions release pattern in time. RESULTS: The total mass of ions released from the appliance into orange juice and Coca Cola(®) (respectively) during the experiment was calculated (µg): Ni (15.33; 37.75), Cr (3.604; 1.052), Fe (48.42; ≥ 156.1), Cu (57.87, 32.91), Mn (9.164; 41.16), Mo (9.999; 30.12), and Cd (0.5967; 2.173). CONCLUSIONS: It was found that orange juice did not intensify the release of metal ions from orthodontic appliances, whereas Coca Cola(®) caused increased release of Ni ions.