RESUMEN
Informal e-waste recycling activities results in serious environmental pollution of PAHs. We evaluated the body burden of 16 PAH congeners and potential health risks for children. A total of 167 children from exposed and reference area entered this study. Child blood samples were collected; height, weight, head and chest circumferences were measured. Blood PAH and lead concentrations were determined. The blood median of total PAHs from the exposed group was significantly higher than the reference group (68.53µg/L vs. 26.92µg/L, P<0.01). The major sources of Σ16-PAH and Σ7 carcinogenic-PAH were residence adjacent to e-waste workshop, paternal occupation related to e-waste recycling and house as a workshop. Inverse correlations were observed in the age and milk consumption with these two PAH groups, while a positive association was found between BMI and Σ7 carcinogenic-PAH, and between child height and blood lead. When divided into high and low exposure groups by Σ16-PAH, a significant negative association was found between body height and blood PAHs (ß and 95%CI: -3.838, -6.469 to -1.206), while for weight and chest circumferences, negative associations were obtained only in the male subgroup before adjustment. After adjustment by sex, age, child milk products consumption per month and blood lead, child height was negatively associated with Σ16-PAH (ß and 95%CI: -3.884, -6.736 to -1.033). Same trends were observed for child chest circumference (ß and 95%CI: -1.147, -2.229 to -0.065). We suggest a negative association of PAHs and child height and chest circumference, while the correlation is more obvious in boys.
Asunto(s)
Desarrollo Infantil/efectos de los fármacos , Residuos Electrónicos/análisis , Contaminantes Ambientales/análisis , Plomo/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Reciclaje , Estatura/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Niño , Preescolar , China , Ciudades , Monitoreo del Ambiente , Contaminantes Ambientales/farmacocinética , Femenino , Humanos , Plomo/farmacocinética , Masculino , Hidrocarburos Policíclicos Aromáticos/farmacocinéticaRESUMEN
In utero co-exposure to endocrine disrupting compounds can perturb fetal development. However, the effect of co-exposure on pivotal regulatory genes has seldom been investigated. We explored the effects of in utero co-exposure to cadmium (Cd), bisphenol A (BPA) and polychlorinated biphenyls (PCBs) on master regulator genes. We recruited 284 healthy pregnant women, of whom 262 provided both cord blood and placenta samples, and 200 had all measurements taken. Placental Cd, cord blood BPA and total PCBs in the exposed group were higher than a reference group. KISS1 expression level in placental tissue was threefold higher in the exposed group than in the reference, and was positively associated with all toxicants. Leptin and leptin receptor expression were also significantly higher, but were only associated with BPA. From our findings, we conclude that lower birth weight is correlated with Cd and PCBs, and may result from the increased KISS1 mRNA expression.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Cadmio/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Fenoles/toxicidad , Placenta/efectos de los fármacos , Bifenilos Policlorados/toxicidad , Resultado del Embarazo , Compuestos de Bencidrilo/sangre , Cadmio/sangre , Femenino , Sangre Fetal/química , Expresión Génica/efectos de los fármacos , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Kisspeptinas/genética , Leptina/genética , Masculino , Fenoles/sangre , Placenta/química , Placenta/metabolismo , Bifenilos Policlorados/sangre , Embarazo , Estudios Prospectivos , ARN Mensajero/análisis , Receptores de Leptina/genéticaRESUMEN
ZnO nanoparticles (ZnO-NPs) are widely used in the engineering and cosmetic industries, and inhaled airborne particles pose a known hazard to human health; their translocation into humans is a recognized public health concern. The pulmonary-blood pathway for ZnO-NP toxicity is well documented, but whether translocation of these particles can also occur via an olfactory bulb-brain route remains unclear. The potential toxicity of ZnO-NPs for the human central nervous system (CNS) is predicated on the possibility of their translocation. Our study investigated translocation of ZnO-NPs both in vitro using the neuronal cell line PC12 and in vivo in a Sprague-Dawley rat model. Our findings indicate that the zinc-binding dye, Newport-Green DCF, binds ZnO stoichiometrically and that ZnO-NP concentration can therefore be measured by the fluorescence intensity of the bound dye in confocal fluorescence microscopy. Confocal data obtained using Newport-Green DCF-2 K(+)-conjugated ZnO-NPs along with the membrane probe FM1-43 demonstrated endocytosis of ZnO-NPs by PC12 cells. In addition, Fluozin-3 measurement showed elevation of cytosolic Zn(2+) concentration in these cells. Following in vivo nasal exposure of rats to airborne ZnO-NPs, olfactory bulbs and brains that were examined by Newport-Green fluorescence and TEM particle measurement clearly showed the presence of ZnO-NPs in brain. We conclude that an olfactory bulb-brain translocation pathway for airborne ZnO-NPs exists in rats, and that endocytosis is required for interneuron translocation of these particles.
Asunto(s)
Endocitosis/fisiología , Nanopartículas/toxicidad , Bulbo Olfatorio/efectos de los fármacos , Neuronas Receptoras Olfatorias/efectos de los fármacos , Óxido de Zinc/toxicidad , Animales , Endocitosis/efectos de los fármacos , Nanopartículas/administración & dosificación , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Bulbo Olfatorio/citología , Neuronas Receptoras Olfatorias/metabolismo , Neuronas Receptoras Olfatorias/ultraestructura , Células PC12 , Material Particulado/administración & dosificación , Material Particulado/farmacocinética , Material Particulado/toxicidad , Ratas , Ratas Sprague-Dawley , Óxido de Zinc/administración & dosificación , Óxido de Zinc/farmacocinéticaRESUMEN
The complex composition of welding fumes, multiplicity of molecular targets, diverse cellular effects, and lifestyles associated with laborers vastly complicate the assessment of welding fume exposure. The urinary metabolomic profiles of 35 male welders and 16 male office workers at a Taiwanese shipyard were characterized via (1)H NMR spectroscopy and pattern recognition methods. Blood samples for the same 51 individuals were also collected, and the expression levels of the cytokines and other inflammatory markers were examined. This study dichotomized the welding exposure variable into high (welders) versus low (office workers) exposures to examine the differences of continuous outcome markers-metabolites and inflammatory markers-between the two groups. Fume particle assessments showed that welders were exposed to different concentrations of chromium, nickel, and manganese particles. Multivariate statistical analysis of urinary metabolomic patterns showed higher levels of glycine, taurine, betaine/TMAO, serine, S-sulfocysteine, hippurate, gluconate, creatinine, and acetone and lower levels of creatine among welders, while only TNF-α was significantly associated with welding fume exposure among all cytokines and other inflammatory markers measured. Of the identified metabolites, the higher levels of glycine, taurine, and betaine among welders were suspected to play some roles in modulating inflammatory and oxidative tissue injury processes. In this metabolomics experiment, we also discovered that the association of the identified metabolites with welding exposure was confounded by smoking, but not with drinking, which is a finding consistent with known modified response of inflammatory markers among smokers. Our results correspond with prior studies that utilized nonmetabolomic analytical techniques and suggest that the metabolomic profiling is an efficient method to characterize the overall effect of welding fume exposure and other confounders.
Asunto(s)
Contaminantes Ocupacionales del Aire , Metales Pesados , Exposición Profesional/análisis , Contaminantes Ocupacionales del Aire/análisis , Consumo de Bebidas Alcohólicas/metabolismo , Biomarcadores/sangre , Biomarcadores/orina , Citocinas/metabolismo , Monitoreo del Ambiente , Humanos , Recuento de Leucocitos , Espectroscopía de Resonancia Magnética , Masculino , Metabolómica , Metales Pesados/análisis , Análisis Multivariante , Líquido del Lavado Nasal/citología , Fumar/metabolismo , Taiwán , SoldaduraRESUMEN
The toxicological effects of zinc oxide nanoparticles (ZnO-NPs) are attracting increasing concern as the field of nanotechnology progresses. Although the literature suggests that toxicity of ZnO-NPs may be related to their dissolution, the mechanism for ZnO-NP perturbation of cytosolic zinc concentration ([Zn(2+)](c)) homeostasis remains obscure. Using FluoZin-3 and RhodZin-3, this study investigated changes in both [Zn(2+)](c) and mitochondrial free Zn(2+) concentration ([Zn(2+)](m)) under conditions of ZnO-NP treatment in vivo and in vitro. In human leukemia Jurkat cells and human lung carcinoma H1355 cells, ZnO-NP treatment resulted in an elevation of both [Zn(2+)](c) and [Zn(2+)](m). In H1355 cells, ZnO-NP treatment induced depolarization of mitochondrial membrane potential, as well as caspase-3 activation and lactic dehydrogenase (LDH) release. In our in vivo experiments, when rats were exposed to ZnO-NPs, higher [Zn(2+)](c) and [Zn(2+)](m) were recorded in both broncho-alveolar lavage (BAL) cells and white blood cells isolated from ZnO-NP-exposed rats, compared with high efficiency particulate air-filter-protected controls LDH levels were also elevated in the BAL of ZnO-NP-exposed rats compared with controls. A mechanical toxicological pathway for ZnO-NP toxicity is suggested by these results: an elevation in [Zn(2+)](c) resulting from ZnO-NP dissolution in the intracellular endosome; cytosolic Zn(2+) sequestration by mitochondria; and elevated [Zn(2+)](m) leading to mitochondrial dysfunction, caspase activation, and cell apoptosis. We conclude that exposure to ZnO-NPs interferes with the homeostasis of [Zn(2+)](c,) and that elevated [Zn(2+)](c) results in cell apoptosis.
Asunto(s)
Leucocitos/efectos de los fármacos , Pulmón/efectos de los fármacos , Nanopartículas , Óxido de Zinc/toxicidad , Animales , Apoptosis/efectos de los fármacos , Líquido del Lavado Bronquioalveolar/química , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Homeostasis , Humanos , Exposición por Inhalación , Células Jurkat , L-Lactato Deshidrogenasa/metabolismo , Leucocitos/metabolismo , Leucocitos/patología , Pulmón/metabolismo , Pulmón/patología , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Óxido de Zinc/metabolismoRESUMEN
Occupational exposure to toluene diisocyanats (TDI) may cause asthma. In asthma patients, the allergic syndromes correlate cytokine production with the elevation in cytosolic calcium concentration [Ca(2+)](c) of lymphocytes in airway. We previously found TDI induces calcium signaling in neuronal cells. TDI mainly gets into human body via inhalation; therefore this study investigated the possibility of TDI inducing the changes in [Ca(2+)](c) in airway. We used human lung epithelial cell line H1355, human T-cell line Jurkat, and human neuroblastoma SH-SY5Y cells to present the kinds of cells existing in airway. The changes of [Ca(2+)](c) were measured by Fura-2 fluorescent dye. Results show that TDI induced an elevation in [Ca(2+)](c )in those cell lines and two primary isolated cells, bovine adrenal chromaffin cells and human white blood cells. Cytokine release and their gene expressions of Jurkat cells and human white blood cells were measured by ELISA and reverse transcription polymerase chain reaction. TDI acutely promoted the interleukine-4 (IL-4) release significantly in both Jurkat cells and human white blood cells. TDI-induced IL-4 release was suppressed in the presence of 1,2-bis- (O-aminophenoxy)ethane-N,N,N',N'- tetraacetic acid (BAPTA), an intracellular Ca(2+) chelator, in Jurkat cells. In the hand of gene expression, TDI induced an increase in the mRNA level of TNF-alpha and IL-4 in Jurkat cells. We conclude that the release of IL-4 were coupled with the elevation in [Ca(2+)](c) induced by TDI. Further studies are required to clarify the roles of TDI-induced IL-4 secretion in acute inflammation.
Asunto(s)
Calcio/metabolismo , Interleucina-4/biosíntesis , 2,4-Diisocianato de Tolueno/toxicidad , Animales , Bovinos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Humanos , Hipersensibilidad/inmunología , Interleucina-4/genética , Células Jurkat , ARN Mensajero/análisisRESUMEN
PURPOSE: To investigate the effects of 1,4-dichlorobenzene (1,4-DCB) on kidney, liver, and hematological functions of workers in insect repellent factories in Taiwan. METHODS: A cross-sectional study was performed comparing 46 exposed workers and 29 non-exposed workers. Health information was collected using questionnaires and biochemical tests. The concentration of urinary 2,5-dichlorophenol (2,5-DCP), the major metabolite of 1,4-DCB, was analyzed by gas chromatography with electron-capture detection. RESULTS: Urinary 2,5-DCP concentration, white blood cell (WBC) count, and serum alanine aminotransferase (ALT) level were higher in exposed workers than in non-exposed ones (P < 0.05). Furthermore, the WBC count and ALT level were significantly correlated with the concentration of 2,5-DCP in urine (P < 0.05). The blood urea nitrogen was significantly higher in on-site exposed workers (P < 0.05). Urinary 2,5-DCP concentration was significantly lower in workers who wore personal protective equipment (PPE) during work than in those who did not (P < 0.05). CONCLUSIONS: The higher urinary 2,5-DCP concentration in exposed (105.38 µg/L) than non-exposed (1.08 µg/L) workers suggests that 1,4-DCB exposure may increase the 2,5-DCP concentration in urine. Moreover, exposure to 1,4-DCB may also increase WBC count and ALT activity, and PPE may protect workers from 1,4-DCB exposure.
Asunto(s)
Clorobencenos/toxicidad , Clorofenoles/orina , Riñón/efectos de los fármacos , Recuento de Leucocitos , Hígado/efectos de los fármacos , Exposición Profesional , Adulto , Alanina Transaminasa/análisis , Alanina Transaminasa/sangre , Nitrógeno de la Urea Sanguínea , Clorobencenos/metabolismo , Clorofenoles/metabolismo , Estudios Transversales , Femenino , Humanos , Repelentes de Insectos/efectos adversos , Repelentes de Insectos/metabolismo , Masculino , Persona de Mediana Edad , Taiwán , Adulto JovenRESUMEN
para-Dichlorobenzene (DCB), a deodorant and an industrial chemical, is a highly volatile compound and is known to be an indoor air contaminant. Because of its widespread use and volatility, the toxicity of DCB presents a concern to industrial workers and public. Some toxic aspects of DCB have already been focused but its effects on neuronal signal transduction have been hitherto unknown. The effects of DCB on the cytosolic calcium homeostasis are investigated in human neuroblastoma SH-SY5Y cells in this study. DCB, above 200 microM, was found to induce a rise in cytosolic calcium concentration that could not be counteracted by nicotinic acetylcholine receptor (nAChR) and muscarinic acetylcholine receptor (mAChR) antagonists but was partially inhibited by thapsigargin. To understand the actions of DCB on the acetylcholine receptors, we investigated its effects on the changes of cytosolic calcium concentration following nicotinic AChR stimulation with epibatidine and muscarinic AChR stimulation with methacholine in human neuroblastoma SH-SY5Y cells. DCB inhibited the cytosolic calcium concentration rise induced by epibatidine and methacholine with respective IC(50)s of 34 and 294 microM. The inhibitions of DCB were not the same as thapsigargin's inhibition. In the electrophysiological observations, DCB blocked the influx currents induced by epibatidine. Our findings suggest that DCB interferes with the functional activities of AChR, including its coupling influx currents and cytosolic calcium elevations.
Asunto(s)
Calcio/metabolismo , Clorobencenos/toxicidad , Receptores Muscarínicos/efectos de los fármacos , Receptores Nicotínicos/efectos de los fármacos , Canales de Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Citosol/metabolismo , Relación Dosis-Respuesta a Droga , Homeostasis/efectos de los fármacos , Humanos , Microelectrodos , Agonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/farmacología , Neuroblastoma , Agonistas Nicotínicos/farmacología , Antagonistas Nicotínicos/farmacología , Técnicas de Placa-Clamp , Receptores Muscarínicos/metabolismo , Receptores Nicotínicos/metabolismo , Células Tumorales CultivadasRESUMEN
The urinary benzene metabolites, trans, trans-muconic acid (ttMA) and S-phenylmercapturic acid (SPMA), are widely used as benzene exposure biomarkers. The influence of the glutathione S-transferase (GST) genetic polymorphism on the excretion levels of urinary ttMA and/or SPMA has been investigated. The association between dose-related production of urinary benzene metabolites and benzene exposure level was also reported. However, the association between the dose-related productions of urinary benzene metabolites and GST genetic polymorphism was not described in the literature. The purpose of this study was to investigate the association between the GST genetic polymorphism and dose-related production of the two widely used biomarkers, urinary ttMA and SPMA. Seventy male workers in a chemical factory were measured for their benzene exposure levels and provided blood and urine specimens at the end of work-shift. The atmospheric benzene exposure levels of these workers were determined by passive samplers with gas chromatograph mass spectrometer. The urinary ttMA and SPMA levels were quantitated by an online dual-loop cleanup device with an electrospray ionization tandem mass spectrometer. The analyses of GST genotypes, including M(1), T(1), and P(1), were done using PCR. Mean (+/- SD) of benzene exposure levels in participants was 7.2 +/- 15 ppm. The ttMA and SPMA levels in the high benzene exposure group (> or =1 ppm) were higher than those in the low benzene exposure group (<1 ppm; P < 0.001). Among the GST genotypes investigated in this study, the results showed that only the GSTT1 genotype was related to the level and dose-related production of SPMA. Using SPMA for evaluating benzene exposure, the results suggest that the GSTT1 genetic polymorphism, especially in a comparison study between two populations with different GSTT1 genotype frequencies, should be considered. Additionally, the biological exposure index value of SPMA should be set based on the levels of subjects with GSTT1-deficient genotypes for protection of all subjects.
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Acetilcisteína/análogos & derivados , Derivados del Benceno/orina , Glutatión Transferasa/genética , Exposición Profesional/efectos adversos , Polimorfismo Genético , Ácido Sórbico/análogos & derivados , Acetilcisteína/orina , Adulto , Biomarcadores/orina , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Ácido Sórbico/metabolismo , Estadísticas no ParamétricasRESUMEN
The mechanisms of TDI (2,4-toluene diisocyanate)-induced occupational asthma are not fully established. Previous studies have indicated that TDI induces non-specific bronchial hyperreactivity to methacholine and induces contraction of smooth muscle tissue by activating 'capsaicin-sensitive' nerves resulting asthma. Cytosolic-free calcium ion concentrations ([Ca(2+)](c)) are elevated when either capsaicin acts at vanilloid receptors, or methacholine at muscarinic receptors. This study therefore investigated the effects of TDI on Ca(2+) mobilization in human neuroblastoma SH-SY5Y cells. TDI was found to elevate [Ca(2+)](c) by releasing Ca(2+) from the intracellular stores and extracellular Ca(2+) influx. 500 microM TDI induced a net [Ca(2+)](c) increase of 112+/-8 and 78+/-6 nM in the presence and absence of extracellular Ca(2+), respectively. In Ca(2+)-free buffer, TDI induced Ca(2+) release from internal stores to reduce their Ca(2+) content and this reduction was evidenced by a suppression occurring on the [Ca(2+)](c) rise induced by thapsigargin, ionomycin, and methacholine after TDI incubation. In the presence of extracellular Ca(2+), simultaneous exposure to TDI and methacholine led a higher level of [Ca(2+)](c) compared to single methacholine stimulation, that might explain that TDI induces bronchial hyperreactivity to methacholine. We conclude that TDI is capable of interfering the [Ca(2+)](c) homeostasis including releasing Ca(2+) from internal stores and inducing extracellular Ca(2+) influx. The interaction of this novel character and bronchial hyperreactivity need further investigation.
Asunto(s)
Calcio/metabolismo , Homeostasis/efectos de los fármacos , 2,4-Diisocianato de Tolueno/farmacología , Atropina/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Señalización del Calcio/efectos de los fármacos , Línea Celular Tumoral , Citosol/efectos de los fármacos , Citosol/metabolismo , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Ácido Egtácico/farmacología , Retículo Endoplásmico/metabolismo , Hexametonio/farmacología , Humanos , Líquido Intracelular/efectos de los fármacos , Líquido Intracelular/metabolismo , Ionomicina/farmacología , Cloruro de Metacolina/farmacología , Neuroblastoma/metabolismo , Neuroblastoma/patología , Potasio/farmacología , Piridinas/farmacología , Receptor Muscarínico M3/metabolismo , Tapsigargina/farmacología , Verapamilo/farmacologíaRESUMEN
Toluene diisocyanate (TDI) is widely used as a chemical intermediate in the production of polyurethane. TDI-induced asthma is related to its disturbance of acetylcholine activity in most affected workers, but the relevant mechanisms are unclear. Toluene diamine (TDA) is the main metabolite of TDI. TDI and TDA have in common the basic toluene structure. Toluene is an abused solvent affecting neuronal signal transduction by influencing the function of ligand gated ion channel receptors, including nicotinic acetylcholine receptors (nAChR), P2X purinoceptors, [gamma]-aminobutyric acid type A (GABAA) receptors, etc. To understand the actions of TDI and TDA on ligand gated ion channels, we investigated their effects on the changes of cytosolic calcium concentration ([Ca2+]c) while stimulating nAChR in human neuroblastoma SH-SY5Y cells, P2 purinoceptors in PC12 cells, and GABAA receptors in bovine adrenal chromaffin cells. Our results showed that both TDI and TDA suppressed the [Ca2+]c rise induced by the potent nicotinic ligand, epibatidine, in human SH-SY5Y cells. Similar but stronger suppression of ATP-induced [Ca2+]c rise occurred in PC12 cells. TDI and TDA also partially suppressed the [Ca2+] c rise induced by GABA in bovine adrenal chromaffin cells. We conclude that TDI and TDA can act on ligand gated ion channel receptors. Our findings suggest that TDI and TDA might have some neurotoxicity that will need to be investigated.
Asunto(s)
Señalización del Calcio/efectos de los fármacos , Activación del Canal Iónico/efectos de los fármacos , Canales Iónicos/efectos de los fármacos , 2,4-Diisocianato de Tolueno/farmacología , Animales , Calcio/química , Calcio/metabolismo , Catecolaminas/metabolismo , Bovinos , Línea Celular Tumoral , Células Cromafines/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Células HeLa , Humanos , Ligandos , Células PC12 , Fenilendiaminas/farmacología , Ratas , Receptores Colinérgicos/efectos de los fármacos , Receptores de GABA-A/efectos de los fármacos , Receptores Purinérgicos P2/efectos de los fármacosRESUMEN
A recombinant plasmid, pYL-1, containing a tyrosinase gene whose expression is under the control of a phage T5 promoter and 2 lac operators, was constructed. Escherichia coli JM109 harboring pYL-1 was used for production of bacterial melanin. A simple procedure for the isolation and purification of melanin was developed. The ultraviolet (UV)-visible light absorption spectra of melanin prepared by chemical synthesis and derived from different organisms, including bacteria, a plant and an animal source, were determined. Melanins produced by both bacteria and chemical synthesis showed a steady increase of absorption at wavelengths of UV light ranging from approximately 200-400 nm, while melanin derived either from plant or animal sources showed an additional discrete absorption peak at wavelength 280 nm upon a similar steady increase of absorption. This additional absorption peak could be due to the presence of protein-bound melanins in animal and plant sources while a free form of melanin was obtained from bacteria and chemical synthesis. Analysis of the effect of bacterial melanin on the activity of antibiotics against E. coli revealed that the activities of polymyxin B, kanamycin, tetracycline, and ampicillin were markedly reduced in the presence of melanin, whereas the activity of norfloxacin was not affected. The reduction of the antibacterial activity may result directly from the interaction of antibiotics with melanin. However, the mechanism of this interaction remains to be demonstrated.
Asunto(s)
Antibacterianos/farmacología , Melaninas/farmacología , Ampicilina/farmacología , Farmacorresistencia Bacteriana , Escherichia coli/genética , Escherichia coli/metabolismo , Kanamicina/farmacología , Melaninas/química , Melaninas/genética , Melaninas/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Norfloxacino/farmacología , Plásmidos/genética , Polimixina B/farmacología , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacología , Análisis Espectral , Tetraciclina/farmacologíaRESUMEN
Toluene diisocyanate (TDI) is widely used as a chemical intermediate in the production of polyurethane products such as foams, coatings, and elastomers. In exposed workers, chronic inhalation of TDI has resulted in significant decreases in lung function. TDI-induced asthma is related to its disturbance of acetylcholine in most affected workers but the actions of TDI on nicotinic acetylcholine receptors (nAChR) are unclear. In order to understand the role of TDI acting on nAChR, we used human neuroblastoma SH-SY5Y cells to investigate the effects of TDI on cytosolic free calcium concentration ([Ca2+]c) changes under the stimulation of nAChR. The results showed that TDI was capable of inhibiting the [Ca2+]c rise induced by nicotinic ligands, epibatidine, DMPP and nicotine. The inhibition was remained, even increased after chronic treatment of TDI. Our study of TDI acting on human nAChR suggests a possibility that the human nerve system plays some role in the toxicity of TDI in the pulmonary system.