RESUMEN
BACKGROUND: Talc, a hydrous magnesium silicate, often used for genital hygiene purposes, is associated with ovarian carcinoma in case-control studies. Its potential to cause inflammation, injury, and functional changes in cells has been described. A complication of such studies is that talc preparations may be contaminated with other materials. A previous study by (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) used a hamster model to study talc and granite dust exposure effects on various biochemical and cellular inflammatory markers. Our current study accessed key materials used in that 1987 study; we re-analyzed the original talc dust with contemporary scanning electron microscopy and energy dispersive x-ray analysis (SEM/EDX) for contaminants. We also examined the original bronchoalveolar lavage (BAL) cells with polarized light microscopy to quantify cell-associated birefringent particles to gain insight into the talc used. RESULTS: SEM/EDX analyses showed that asbestos fibers, quartz, and toxic metal particulates were below the limits of detection in the original talc powder. However, fibers with aspect ratios ≥3:1 accounted for 22% of instilled material, mostly as fibrous talc. Talc (based on Mg/Si atomic weight % ratio) was the most abundant chemical signature, and magnesium silicates with various other elements made up the remainder. BAL cell counts confirmed the presence of acute inflammation, which followed intratracheal instillation. Measurements of cell associated birefringent particles phagocytosis revealed significant differences among talc, granite, and control exposures with high initial uptake of talc compared to granite, but over the 14-day experiment, talc phagocytosis by lavaged cells was significantly less than that of granite. Phagocytosis of talc fibers by macrophages was observed, and birefringent particles were found in macrophages, neutrophils, and multinucleate giant cells in lavaged cells from talc-exposed animals. CONCLUSION: Our data support the contention that talc, even without asbestos and other known toxic contaminants, may elicit inflammation and contribute to lung disease. Our findings support the conclusions of (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) study. By analyzing particulate exposures with polarized light microscopy and SEM/EDX, fibrous talc was identified and a distinctive pattern of impaired particulate ingestion was demonstrated.
Asunto(s)
Exposición por Inhalación/efectos adversos , Pulmón/efectos de los fármacos , Macrófagos/efectos de los fármacos , Silicatos de Magnesio/toxicidad , Neutrófilos/efectos de los fármacos , Talco/toxicidad , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Células Cultivadas , Cricetinae , Polvo , Exposición por Inhalación/análisis , Pulmón/metabolismo , Pulmón/patología , Macrófagos/metabolismo , Macrófagos/ultraestructura , Silicatos de Magnesio/química , Silicatos de Magnesio/farmacocinética , Masculino , Microscopía Electrónica de Rastreo , Neutrófilos/metabolismo , Neutrófilos/ultraestructura , Tamaño de la Partícula , Cuarzo/química , Cuarzo/farmacocinética , Cuarzo/toxicidad , Dióxido de Silicio/química , Dióxido de Silicio/farmacocinética , Dióxido de Silicio/toxicidad , Espectrometría por Rayos X , Propiedades de Superficie , Talco/química , Talco/farmacocinéticaRESUMEN
The distribution of dust particles within the lungs and their excretion are highly associated with their pulmonary toxicity. Literature was reviewed to discern pulmonary translocation pathways for inhaled α-quartz compared to those for inhaled TiO2. Accordingly, it was hypothesized α-quartz particles in the alveoli were phagocytized by alveolar macrophages but silica-containing macrophages remained in the alveoli for longer time in contrast to the rapid elimination from the alveoli seen for TiO2-containing macrophages. In addition, it was presumed that free silica particles are translocated in the interstitium, possibly through the cytoplasm of Type I epithelial cells, as observed with TiO2. Free silica particles are presumed to be phagocytized by interstitial macrophages soon after the particles penetrate the interstitium; these dust cells are then translocated to the ciliated airway regions in the lumen through bronchus-associated lymphoid tissue (BALT). The pulmonary retention half-time of dust particles in rats exposed to α-quartz is several times longer than that of rats exposed to TiO2, as long as the lung dust burden is ≈ 3 mg. The reduced pulmonary particle clearance ability in rats exposed to α-quartz aerosol is presumably attributed to the long-term retention of dust cells both in the alveoli and in the interstitium; this retention may be caused by the reduced chemotactic abilities of α-quartz-containing dust cells. However, the accumulation of α-quartz-containing dust cells in the lungs is not associated with the occurrence of pulmonary inflammation.
Asunto(s)
Pulmón/metabolismo , Cuarzo/farmacocinética , Administración por Inhalación , Animales , Granuloma/inducido químicamente , Pulmón/efectos de los fármacos , Enfermedades Pulmonares/inducido químicamente , Ganglios Linfáticos/metabolismo , Cuarzo/toxicidad , RatasRESUMEN
Manufactured multi-walled carbon nanotubes (MWCNT) have attracted a great deal of attention due to their unique structural, chemical, and physical characteristics. This study utilized a 1x 6h inhalation exposure protocol followed by a 3 months post-exposure period. Wistar rats were nose-only exposed to 11 and 241 mg/m(3) MWCNT (Baytubes) of respirable, solid aerosol. MWCNT depleted of residual metals (depletion from 0.53% to 0.12% Co) were compared at 11 mg/m(3). Rats similarly exposed to air and alpha-quartz (248 mg/m(3)) served as negative and positive controls, respectively. Pulmonary response was characterized by bronchoalveolar lavage (BAL), lung histopathology, organ burden determinations, and gene expression analyses of lung homogenates with emphasis on extracellular matrix components. This acute inhalation exposure protocol was suitable to characterize and distinguish acute deposition-related effects from the long-term sequelae of retained MWCNT. Subtle differences in acute pulmonary toxic potency due to differences in metal contaminations could be revealed by this protocol. Consistent with the long retention halftime of poorly soluble particles, even short-term inhalation studies may require post-exposure periods of at least 3 months to reveal MWCNT-specific dispositional and toxicological characteristics relative to alpha-quartz. Distinct differences in the time course of pulmonary inflammation of MWCNT and alpha-quartz could be demonstrated. Transcriptomics proved to be a useful tool to analyze the etiopathology of collagen detected by BAL and histopathology. In summary, the pulmonary inflammogenicity following exposure to MWCNT was concentration-dependent with evidence of regression over time. Conversely, alpha-quartz resulted in progressive changes over time. The time course of pulmonary inflammation associated with retained MWCNT was independent on the concentration of residual cobalt. This supports the conclusion that the predominant response to inhaled MWCNT is principally related to the assemblage structure and not catalyst impurities (if in the range of < or = 0.5%).
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Pulmón/efectos de los fármacos , Nanotubos de Carbono/toxicidad , Neumonía/inducido químicamente , Cuarzo/toxicidad , Aerosoles , Remodelación de las Vías Aéreas (Respiratorias)/genética , Animales , Líquido del Lavado Bronquioalveolar/química , Análisis por Conglomerados , Relación Dosis-Respuesta a Droga , Contaminantes Ambientales/química , Contaminantes Ambientales/farmacocinética , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica/efectos de los fármacos , Exposición por Inhalación , Pulmón/metabolismo , Pulmón/patología , Masculino , Estructura Molecular , Nanotubos de Carbono/química , Análisis de Secuencia por Matrices de Oligonucleótidos , Tamaño de los Órganos , Neumonía/genética , Neumonía/metabolismo , Neumonía/patología , Cuarzo/química , Cuarzo/farmacocinética , Ratas , Ratas Wistar , Factores de Tiempo , Distribución TisularRESUMEN
The fate of nano-TiO(2) particles in the body was investigated after inhalation exposure or intravenous (i.v.) injection, and compared with pigmentary TiO(2) and quartz. For this purpose, a 5-day inhalation study (6h/day, head/nose exposure) was carried out in male Wistar rats using nano-TiO(2) (100mg/m(3)), pigmentary TiO(2) (250mg/m(3)) and quartz dust DQ 12 (100mg/m(3)). Deposition in the lung and tissue distribution was evaluated, and histological examination of the respiratory tract was performed upon termination of exposure, and 2 weeks after the last exposure. Broncho-alveolar lavage (BAL) was carried out 3 and 14 days after the last exposure. Rats were also injected with a single intravenous dose of a suspension of TiO(2) in serum (5mg/kg body weight), and tissue content of TiO(2) was determined 1, 14 and 28 days later. The majority of the inhaled nano-TiO(2) was deposited in the lung. Translocation to the mediastinal lymph nodes was also noted, although to smaller amounts than following inhalation of pigmentary TiO(2), but much higher amounts than after exposure to quartz. Systemically available nano-TiO(2), as simulated by the i.v. injection, was trapped mainly in the liver and spleen. The (agglomerate) particle size of lung deposited nano-TiO(2) was virtually the same as in the test atmosphere. Changes in BAL fluid composition and histological examination indicated mild neutrophilic inflammation and activation of macrophages in the lung. The effects were reversible for nano- and pigmentary TiO(2), but progressive for quartz. The effects observed after 5-day inhalation exposure to nano-TiO(2) were qualitatively similar to those reported in sub-chronic studies.
Asunto(s)
Colorantes/farmacocinética , Colorantes/toxicidad , Nanopartículas/toxicidad , Cuarzo/farmacocinética , Cuarzo/toxicidad , Titanio/farmacocinética , Titanio/toxicidad , Administración por Inhalación , Animales , Líquido del Lavado Bronquioalveolar/química , Colorantes/química , Inyecciones Intravenosas , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/metabolismo , Masculino , Nanopartículas/química , Nanopartículas/ultraestructura , Tamaño de la Partícula , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/ultraestructura , Cuarzo/química , Ratas , Ratas Wistar , Distribución Tisular , Titanio/químicaRESUMEN
Inhalation of quartz particles is associated with a variety of adverse lung effects. Since particle surface is considered to be crucial for particle pathogenicity, we investigated the influence of quartz surface properties on lung burden, inflammation (bronchoalveolar lavage cells), and cytotoxicity (protein, lactate dehydrogenase, beta-glucuronidase) 90 days after a single intratracheal instillation of 2 mg DQ12 into rats. The role of particle surface characteristics was investigated by comparative investigation of native versus surface-modified quartz, using polyvinylpyridine N-oxide (PVNO) or aluminum lactate (AL) coating. Uptake and subcellular localization of quartz samples as well as tumor necrosis factor (TNF)-alpha release were determined using NR8383 rat alveolar macrophages. Surface modification of quartz particles resulted in marked in vivo and in vitro changes. Compared to native quartz, modified quartz samples showed lower lung burden at 90 days, as well as decreased inflammatory and cytotoxic responses. Coating with polyvinylpyridine N-oxide (PVNO) appeared to be more effective than aluminium lactate (AL). PVNO-coating of quartz also resulted in an enhanced particle uptake by macrophages up to 24 h, whereas AL coating caused a transient reduction of quartz uptake at 2 h. At 24 h differences with the native quartz were absent. Subcellular localization of quartz particles was not affected by surface modifications. However, surface modification resulted in a reduced release of TNF-alpha. In conclusion, surface properties of quartz particles appear to be crucial for rate and extent of in vitro particle uptake in macrophages. Our in vivo findings also indicate that quartz surface properties may affect clearance kinetics. Particle surface-specific interactions between quartz and macrophages may therefore play a major role in the pulmonary pathogenicity of quartz.
Asunto(s)
Pulmón/metabolismo , Macrófagos Alveolares/metabolismo , Neumonía/metabolismo , Cuarzo/farmacocinética , Animales , Línea Celular Transformada , Femenino , Pulmón/efectos de los fármacos , Pulmón/patología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/patología , Tasa de Depuración Metabólica/efectos de los fármacos , Tasa de Depuración Metabólica/fisiología , Neumonía/inducido químicamente , Neumonía/patología , Cuarzo/toxicidad , Ratas , Ratas Wistar , Propiedades de Superficie/efectos de los fármacosRESUMEN
Quartz (crystalline silica) is not consistently carcinogenic across different industries where similar quartz exposure occurs. In addition, there are reports that surface modification of quartz affects its cytotoxicity, inflammogenicity, and fibrogenicity. Taken together, these data suggest that the carcinogenicity of quartz is also related to particle surface characteristics, and so we determined the genotoxic effects of DQ12 quartz particles versus DQ12 whose surface was modified by treating with either aluminum lactate or polyvinylpyridine-N-oxide (PVNO). The different particle preparations were characterized for hydroxyl-radical generation using electron spin resonance (ESR). DNA damage was determined by immunocytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG) and the alkaline comet-assay using A549 human lung epithelial cells. Cytotoxicity was measured using the LDH- and MTT-assays, and particle uptake by the A549 cells was quantified by light microscopy, using digital light imaging evaluation of 800 nm sections. The ability of quartz to generate hydroxyl-radicals in the presence of hydrogen peroxide was markedly reduced upon surface modification with aluminum lactate or PVNO. DNA strand breakage and 8-OHdG formation, as produced by quartz at nontoxic concentrations, could be completely prevented by both coating materials. Particle uptake into A549 cells appeared to be significantly inhibited by the PVNO-coating, and to a lesser extent by the aluminum-lactate coating. Our data demonstrate that respirable quartz particles induce oxidative DNA damage in human lung epithelial cells and indicates that surface properties of the quartz as well as particle uptake by these target cells are important in the cytotoxic and the genotoxic effects of quartz in vitro.
Asunto(s)
Daño del ADN , Pulmón/metabolismo , Cuarzo/efectos adversos , Cuarzo/antagonistas & inhibidores , Supervivencia Celular , Células Cultivadas , Ensayo Cometa , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análisis , Espectroscopía de Resonancia por Spin del Electrón , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Humanos , Radical Hidroxilo/análisis , Inmunohistoquímica , L-Lactato Deshidrogenasa/análisis , Pulmón/citología , Pulmón/efectos de los fármacos , Oxidación-Reducción , Tamaño de la Partícula , Cuarzo/farmacocinética , Propiedades de SuperficieRESUMEN
The review deals with the problems of development of analytical equipment based on piezoelectric crystals. Consideration is given to the philosophy of determining inorganic and organic compounds, biologically active compounds, viruses, and bacteria with piezoelectric resonators. Described are methods of immobilization of the biological component, immersion-and-drying analysis, and sensor-assisted detection in the soluble phase.
Asunto(s)
Absorción , Técnicas Biosensibles/métodos , Gases/análisis , Gases/farmacocinética , Periodicidad , Soluciones/análisis , Soluciones/farmacocinética , Anticuerpos/metabolismo , Toxinas Bacterianas/metabolismo , Electrodos , Compuestos Inorgánicos/análisis , Compuestos Inorgánicos/farmacocinética , Compuestos Orgánicos/análisis , Compuestos Orgánicos/farmacocinética , Cuarzo/análisis , Cuarzo/farmacocinéticaRESUMEN
Lung surfactant serves as a protective coating when adsorbed on particle surfaces, so its removal or rate of removal in vivo may affect expression of mineral cytotoxicity. Removal of phospholipid surfactant components from the surface of mineral particles ingested by alveolar macrophages (AM) was measured using fluorescence microscopy. Dipalmitoylphosphatidylcholine with a fluorescent label (BODIPY(trade mark)) substituted for C1-C4 on the second acyl chain (DPPC*), was mixed with dioleoylphosphatidylcholine (DOPC) to coat respirable quartz and kaolin particles. Fluorescence from quartz or kaolin particles of 3-4, 5-6 and 8-9 microm size decreased in intensity with increasing ratios of DOPC/DPPC* for the same DOPC concentration of 0.4 mg/ml. There was a direct correlation between fluorescence and residual phospholipid surfactant remaining on particles using phospholipase A2 (PLA(2)) digestion in a cell-free system, indicating that the presence of the fluorophore on DPPC did not hinder enzymatic recognition. Lavaged primary AM obtained from male Fischer rats were challenged in vitro with DOPC/DPPC* (10:1 mol:mol) coated particles at 50 microg particles/10(6) cells. In contrast to the biexponential response seen in cell-free experiments, the rate of fluorescence decay from ingested coated quartz or kaolin particles over 7 days was monoexponential, with the same t(1/2) (41 h) for each dust. This study suggests that the rate of phagolysosomal digestion and removal of the adsorbed surfactant is not a determinant of the different mineral-specific pathogenicities or toxicities of quartz and kaolin, although residual fluorescence remained on particles even after 7-8 days.
Asunto(s)
Caolín/farmacocinética , Macrófagos Alveolares/metabolismo , Surfactantes Pulmonares/farmacocinética , Cuarzo/farmacocinética , 1,2-Dipalmitoilfosfatidilcolina/farmacocinética , Animales , Disponibilidad Biológica , Células Cultivadas , Polvo , Caolín/toxicidad , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/fisiología , Masculino , Microscopía Fluorescente/métodos , Fagocitosis/efectos de los fármacos , Fagocitosis/fisiología , Fosfatidilcolinas/farmacocinética , Fosfolipasas A/metabolismo , Fosfolipasas A2 , Fosfolípidos/metabolismo , Cuarzo/toxicidad , Ratas , Ratas Endogámicas F344RESUMEN
The purpose of this study was to assess the bioavailability and pulmonary toxicity of ZnCdS in rats. Groups of 30 male Fischer 344 rats each were anesthetized and dosed via intratracheal instillation with 5 mg of either ZnCdS, quartz (positive control), or titanium dioxide (TiO(2), negative control) suspended in 0.5 ml saline. A vehicle control group received 0.5 ml saline. Ten animals from each test group were sacrificed at 1 day, 1 wk, and 14 wk after dosing for bronchoalveolar lavage fluid (BALF) analysis and histopathology. The BALF was analyzed for alkaline phosphatase, acid phosphatase, lactate dehydrogenase (LDH), beta-glucuronidase (beta-glu), total protein, and cell counts. Two separate groups of 24 rats each were dosed as already described with either ZnCdS or saline. Eight rats from each group were sacrificed at 1 day, 1 wk, and 14 wk after dosing for determination of cadmium (Cd) and zinc (Zn) concentrations in the lung, liver, kidney, and blood. Results indicate that at 1 day after dosing, all enzyme activities (except acid phosphatase) and cell counts in BALF from the quartz and ZnCdS groups were significantly higher than in the TiO(2) and saline groups. At 7 days after dosing, high enzyme activity persisted in the quartz group, while the ZnCdS group showed only LDH and total protein levels significantly higher than the saline group. At 14 wk after dosing, LDH, total protein, beta-glu, and cell counts in the quartz group were significantly higher than all other groups. Histologic examination revealed interstitial inflammation and accumulation of foreign material in the lungs and mediastinal lymph nodes of quartz-, TiO(2)-, and ZnCdS-treated rats. Metal analyses in tissues showed profuse Cd and Zn concentrations in the lung 1 day after dosing, followed by a successive decline at 7 days and 14 wk after dosing. A very small, but statistically significant, amount of Cd and Zn was found in the kidneys at 14 wk after dosing. In conclusion, ZnCdS appears to cause temporary lung inflammation, is cleared slowly, and is poorly bioavailable.
Asunto(s)
Pulmón/efectos de los fármacos , Sulfuros/toxicidad , Tráquea/efectos de los fármacos , Fosfatasa Ácida/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Disponibilidad Biológica , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Cadmio/administración & dosificación , Cadmio/toxicidad , Recuento de Células , Estudios de Factibilidad , Glucuronidasa/metabolismo , Intubación Intratraqueal , L-Lactato Deshidrogenasa/metabolismo , Pulmón/metabolismo , Pulmón/patología , Neumoconiosis/etiología , Neumoconiosis/patología , Cuarzo/administración & dosificación , Cuarzo/farmacocinética , Cuarzo/toxicidad , Ratas , Ratas Endogámicas F344 , Sulfuros/administración & dosificación , Titanio/administración & dosificación , Titanio/farmacocinética , Titanio/toxicidad , Zinc/administración & dosificación , Zinc/toxicidadRESUMEN
In recent years, a physiology-oriented multicompartmental kinetics (POCK) model was developed to simulate pulmonary retention data of biopersistent, noncytotoxic aerosols in long-term inhalation exposures of rats. Experimental data were successfully simulated for submicrometer-sized aerosols like carbon black, diesel soot, and titanium dioxide and for a micrometer-sized xerographic toner aerosol (Stöber et al., 1994, 1995). This article describes for various rat strains successful POCK model simulations of experimental pulmonary retention data of micrometer-sized aerosols of biopersistent cytotoxic SiO2 modifications like quartz and quartzite. In the past, the POCK model was not applied to cytotoxic aerosols and dusts. Cytotoxicity was considered incompatible with the model assumption of a constant macrophage lifetime independent of the macrophage aerosol load. The few relevant experimental retention studies with biopersistent silica found in the open literature showed particulate lung burdens up to some 15 mg per rat lung. Apparently, at these loads, pulmonary burdens could be simulated because the fraction of alveolar macrophages killed by the cytotoxic particles was possibly still small compared to the total number of viable macrophages. Of necessity, however, the classical alveolar clearance in these studies was exclusively performed by alveolar macrophages that were burdened with cytotoxic particles, and the cells appeared to suffer from a substantial initial decrease of their inherent mobility. Thus a sizeable reduction of the alveolar clearance rate coefficient in comparison to nontoxic aerosol was found. The results for the model parameters of several different exposure studies are shown and interpreted in comparison to nontoxic titanium dioxide retention parameters.
Asunto(s)
Simulación por Computador , Polvo/efectos adversos , Exposición por Inhalación/efectos adversos , Pulmón/metabolismo , Modelos Teóricos , Neumoconiosis/metabolismo , Cuarzo/farmacocinética , Administración por Inhalación , Aerosoles , Animales , Carga Corporal (Radioterapia) , Femenino , Pulmón/efectos de los fármacos , Pulmón/patología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patología , Masculino , Neumoconiosis/etiología , Cuarzo/administración & dosificación , Cuarzo/toxicidad , Ratas , Ratas Endogámicas F344 , Titanio/administración & dosificación , Titanio/farmacocinéticaRESUMEN
Respirable-sized quartz was treated with a saline dispersion of dipalmitoyl phosphatidylcholine (DPPC), a primary component of pulmonary surfactant, to model the adsorption of phospholipid surfactant onto quartz dust following particle deposition in the bronchoalveolar region of the lung. Control and surfactant-treated dusts were used to challenge lavaged rat pulmonary macrophages in vitro over a 1-week period, to determine the effects of adsorbed surfactant on the expression of quartz cytotoxicity and genotoxicity. DNA damage was determined by the single cell gel electrophoresis 'comet' assay. Untreated quartz induced DNA damage, increasing with dose and with time of incubation of dust with macrophages over a 5 day period. DPPC treatment of quartz suppressed DNA damage through 1 day of macrophage challenge. DNA damage then increased over a 5 day period, to approximately half the positive control (untreated quartz) values. Cytotoxicity was measured by trypan blue dye exclusion and by the Live-Dead fluorescence assay for cell viability. Cytotoxicity of surfactant-treated quartz measured one day after challenge of lavaged macrophages was suppressed to values near those of the negative controls, and then increased over a 1 week incubation period to levels near those expressed by native quartz positive controls. Quartz similarly treated with dioleoyl phosphatidylcholine mixed with DPPC substituted in one acyl group with a boron-containing fluorescent chromophore was used with confocal microscopy to measure particle-associated fluorescent surfactant in cells. Approximately half of the fluorescence intensity was lost over a 1 week period following challenge of lavaged macrophage. Results are discussed in terms of a model of restoration of quartz particle surface toxicity as prophylactic surfactant is removed from particle surface by cellular enzymatic digestion processes.
Asunto(s)
1,2-Dipalmitoilfosfatidilcolina/farmacocinética , 1,2-Dipalmitoilfosfatidilcolina/toxicidad , Daño del ADN , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Surfactantes Pulmonares/farmacocinética , Surfactantes Pulmonares/toxicidad , Cuarzo/farmacocinética , Cuarzo/toxicidad , Adsorción , Animales , Células Cultivadas , Masculino , Microscopía Fluorescente , Surfactantes Pulmonares/química , Cuarzo/química , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Toxic potency of quartz-containing dusts, including coal mine dusts, is usually inhibited by protective clay mineral layers on the surface of quartz particles. This investigation of 11 dusts recovered from lungs of coal miners with different silicosis grade shows that such layers persist during long-term contact with human lung tissues. On the other hand, the results suggest that an apparently preferential release of iron occurred in lungs with massive fibrosis. These preliminary results support the hypothesis of an iron-related harmfulness of coal mine dusts.
Asunto(s)
Minas de Carbón , Polvo , Hierro/metabolismo , Pulmón/metabolismo , Minerales/farmacocinética , Silicosis/metabolismo , Humanos , Cuarzo/farmacocinética , Factores de TiempoRESUMEN
Changes in the metabolism of rat alveolar macrophages exposed to quartz and coal dusts were studied by biochemical methods. The intratracheal administration of quartz and coal dusts in 6 hours induced the augmented storage of glycoproteins on the cell surface and the increased lysosomal enzymes (beta-galactosidase, beta-glucuronidase) activities. The quartz dust also induced the decrease of hexauronic acids level. The interaction of macrophage with the fibrogenic dust (quartz) may cause severe disorders in the balance of carbohydrate constituents of glycocalyx, which impairs the vitality of alveolar macrophages.
Asunto(s)
Carbón Mineral , Polvo , Glicoproteínas/metabolismo , Macrófagos Alveolares/metabolismo , Cuarzo/farmacocinética , Animales , Biotransformación , Glucuronidasa/efectos de los fármacos , Glucuronidasa/metabolismo , Glicoproteínas/efectos de los fármacos , Ácidos Hexurónicos/metabolismo , Intubación Intratraqueal , Macrófagos Alveolares/efectos de los fármacos , Ratas , Factores de Tiempo , beta-Galactosidasa/efectos de los fármacos , beta-Galactosidasa/metabolismoRESUMEN
Respirable-sized quartz, a well-established fibrogenic mineral dust, is compared with kaolin in erythrocyte hemolysis assays after treatment with saline dispersion of dipalmitoyl phosphatidylcholine, a primary phospholipid component of pulmonary surfactant. Both dusts are rendered inactive after treatment, but the membranolytic activity is partly to fully restored after treatment with phospholipase A2, an enzyme normally associated with cellular plasma membranes and lysosomes. Phospholipid-coated dusts were incubated for periods of 2-72 h at a series of applied enzyme concentrations, and the adsorbed lipid species and hemolytic activity were quantitated at each time for both dusts. Surfactant was lost more readily from quartz than from kaolin, with consequent more rapid restoration of mineral surface hemolytic activity for quartz. Interactions of surfactant and mineral surface functional groups responsible for the mineral-specific rate differences, and implications for determining the mineral surface bioavailability of silica and silicate dusts, are discussed.
Asunto(s)
1,2-Dipalmitoilfosfatidilcolina/farmacocinética , Membrana Eritrocítica/efectos de los fármacos , Caolín/farmacocinética , Caolín/toxicidad , Fosfolipasas A/metabolismo , Cuarzo/farmacocinética , Cuarzo/toxicidad , 1,2-Dipalmitoilfosfatidilcolina/metabolismo , Adsorción , Animales , Disponibilidad Biológica , Cromatografía en Capa Delgada , Polvo , Eritrocitos/efectos de los fármacos , Hemólisis , Lisofosfatidilcolinas/metabolismo , Lisofosfatidilcolinas/farmacocinética , Fosfolipasas A/efectos de los fármacos , Fosfolipasas A2 , OvinosRESUMEN
To investigate the long term effects of quartz, bronchoalveolar lavage (BAL) and analysis of lung silica were performed in rats (n = 20) one, four, and 12 months after exposure to intratracheally instilled crystalline silica. Total and relative concentrations of silica in the lungs were highest one month after exposure. At this time BAL fluid concentrations of total cells, macrophages, and lymphocytes increased five to 10-fold compared with saline instilled controls (n = 19). The number of polymorphonuclear cells (PMNs) increased about 200-fold. The increased number of PMNs persisted during the year. Furthermore, albumin and fibronectin concentrations increased continually during the year, about two to fivefold the values of controls. Hyaluronan, by contrast, increased during the four month period (about eightfold) but decreased after one year to the one month concentration. Phospholipids in BAL fluid, raised already after one month, remained high at one year. The findings suggest progressive damage of the alveolar and interstitial tissues. Moreover, the increases in components of the extracellular matrix capable of building fibrotic networks are in agreement with the microscopical findings of fibrosis. Because only total cells, macrophages, and albumin concentrations correlated weakly with the silica contents of the lung, it is unlikely that the relation between quartz burden and the reaction in the lung is simple.
Asunto(s)
Líquido del Lavado Bronquioalveolar/metabolismo , Matriz Extracelular/metabolismo , Pulmón/patología , Neumonía/etiología , Cuarzo/efectos adversos , Animales , Líquido del Lavado Bronquioalveolar/patología , Femenino , Fibrosis , Pulmón/metabolismo , Neumonía/metabolismo , Cuarzo/farmacocinética , Ratas , Ratas EndogámicasRESUMEN
The two silicon dioxide polymorphs, quartz and cristobalite, are known to have different toxicities. The clearance kinetics and biological response of two sources of quartz and one source of pure cristobalite were compared. Models were also developed to show the accumulation of cristobalite in the lungs of Fischer 344 rats as the result of short-term exposures at three different concentrations. The amount of cristobalite cleared from the lung was considerably less than that of the two quartz materials, with little or no clearance after the initial 30 days post exposure. As an indicator of the cellular biological response to the aerosols, total and differential cell counts were measured on bronchoalveolar lavage specimens. Cristobalite showed an early and sustained response with an elevated macrophage, neutrophil, and lymphocyte count through 180 days post exposure. The two quartz materials were not identical in their biological behavior even though they had identical crystal structure and similar trace element analysis. One quartz sample (MIN5) showed an increase in cell response (macrophage, neutrophils, and lymphocytes) approximately 30% that of cristobalite, whereas the other quartz material was not significantly different from control values. In addition, lung hydroxyproline content was greater in the cristobalite-exposed animals.
Asunto(s)
Pulmón/metabolismo , Cuarzo/farmacocinética , Dióxido de Silicio/farmacocinética , Animales , Recuento de Células Sanguíneas , Líquido del Lavado Bronquioalveolar/citología , Pulmón/fisiología , Masculino , Modelos Biológicos , Cuarzo/toxicidad , Ratas , Ratas Endogámicas F344 , Dióxido de Silicio/toxicidadRESUMEN
The purposes of this study were (1) to investigate the chronology of events in cellular and biochemical changes thought to be important in the development of silicosis, (2) to relate these to changes in lung function and radiograph, and (3) to evaluate the relation of quartz exposure and retention to individual response leading to early silicosis. Thirty-six sheep were exposed by repeated intratracheal infusion at 10-day intervals to 100 mg Minusil-5 in 100 ml saline (Si group), and 10 sheep were exposed at the same intervals to 100 ml saline (control). All sheep were investigated at 3-month intervals by chest radiograph, lung function, and lung lavage. At month 9, chest radiograph score of parenchymal opacities was significantly increased at 2.8 +/- 0.6 versus 0.4 +/- 0.4 in the Si group (p less than .05), establishing early radiologic silicosis. Lung function was significantly altered with reduction in lung compliance, vital capacity, and diffusion capacity (p less than .05). Lung lavage cellularity revealed significant increase in total cells (X 2.5), macrophages (X3), and neutrophils (X3). Albumin in BAL remained at the control level. Fibronectin production was significantly increased, as was the fibroblast growth activity, without significant change in procollagen 3 at this early stage of disease. Total phospholipids were significantly elevated in the Si-exposed sheep, and the profile demonstrated an increase in all the phospholipid components. Spontaneous release of hydrogen peroxide by alveolar cells was not increased, but in the presence of phorbol myristate acetate (PMA) higher levels of peroxide were found in the quartz-exposed sheep (p less than .05). The cellular and biochemical alterations of lung lavage preceded other changes. At month 12, there were good correlations (r greater than .49, p less than .001) between parameters evaluating related phenomena but poor correlations between measurements evaluating different aspects of the disorder. To investigate the heterogeneity in the individual response of sheep to the same exposure (susceptibility), individual quartz retention levels at month 12 were measured and found to correlate well with individual parameters of disease activity. We concluded that in early silicosis of sheep, cellular and biochemical changes in lung lavage preceded derangements of pulmonary function and radiographic abnormalities. Thereafter, parameters of lung lavage, lung function, and radiograph were significantly interrelated, but for a given exposure the degree of quartz retention appeared to determine the intensity of the silicotic process.
Asunto(s)
Pulmón/fisiopatología , Cuarzo/toxicidad , Dióxido de Silicio/toxicidad , Silicosis/metabolismo , Animales , Líquido del Lavado Bronquioalveolar , Células Cultivadas , Pulmón/citología , Pulmón/metabolismo , Masculino , Cuarzo/farmacocinética , Ovinos , Silicosis/fisiopatologíaRESUMEN
SPF F-344 rats were exposed 6 h/day 5 days/wk for up to 24 months to a special test toner at 0, 1, 4 and 16 mg/m3 or TiO2 at 5 mg/m3, or SiO2 at 1 mg/m3, by the inhalation route. The animals were kept for an additional 6 weeks in filtered air. Surviving animals were sacrificed at 25.5 months after start of exposure. Life-span and causes of death were independent of treatment and in accordance with published values. No evidence for systemic toxicity or any upper-respiratory system effects were found in the toner-exposed groups. The incidence of lung tumors was comparable in the control, 3 toner and TiO2-exposed groups. An incidence of 18%, combined benign and malignant tumors was observed in the quartz-treated rats. A slight to moderate degree of fibrosis was observed at the toner high exposure level in all animals, while a very slight degree of fibrosis was noted in 20% of the animals at the toner middle (4 mg/m3) exposure level. The fibrogenic potency of the test toner was calculated to be comparable to TiO2. No pulmonary changes were seen at the toner low (1 mg/m3) and environmentally most relevant exposure level.
Asunto(s)
Neoplasias Pulmonares/patología , Administración por Inhalación , Animales , Femenino , Neoplasias Pulmonares/inducido químicamente , Masculino , Metacrilatos/administración & dosificación , Metacrilatos/farmacocinética , Fibrosis Pulmonar/inducido químicamente , Cuarzo/administración & dosificación , Cuarzo/farmacocinética , Ratas , Ratas Endogámicas F344 , Factores de Tiempo , Titanio/administración & dosificación , Titanio/farmacocinéticaRESUMEN
A study is made on the adsorption capacity of several types silicates and quartz dusts, prepared from pure mineral standards with respect to methylene blue and fuchsin. There are differences in the adsorption capacity of the minerals referring to unit surface. The quantity of the adsorption for samples of the same mineral, broken to pieces of different dispersity, also differs. However, between the adsorption capacity of test samples, divided into 3 groups--quartz, zeolite and mixed from the work environment, with respect to methylene blue, and their biological aggressiveness, tested "in vivo" after intratracheal test and the subcutaneous pocket method and the zeolite dusts on diploid culture, an inverse dependence is established. The adsorption capacity of the test dusts from the work environment is many times higher than the examined quartz and zeolite dusts, because of the presence of mineral components in them, especially argillaceous, which have high affinity toward the dye. The inverse dependence established between the adsorption capacity with respect to methylene blue and the biological effect of the tested dusts give grounds to propose the adsorption capacity as one of the induces for studying and hygienic evaluation of different types dusts, which have no components manifesting specific affinity to the dye.