RESUMEN
Microplastics (MPs) have attracted significant attention due to their global distribution in living environments. Although some studies have reported MP-induced hepatotoxicity in mouse models, a systematic approach to MP-mediated liver toxicity was still lacking. Therefore, we used a mouse model to study the sub-chronic effects of MP exposure on the liver. Female C57BL/6 mice, aged 6 weeks, received an oral administration of 0.3 mg of Nile Red-labeled polystyrene (PS) microplastics, with particle sizes of 0.5 µm (submicron) and 5 µm (micron), via gavage, while control mice received vehicle only. Each mouse was exposed to MPs twice a week for 12 weeks. After sacrifice, the levels of MP accumulation, oxidative stress, inflammation, and pathological changes were measured in the mouse liver, and blood samples were collected for serum biochemistry analysis. Our results demonstrated that 0.5 µm PS-MPs were accumulated in mouse livers post-MP exposure, but not in the 5 µm MP exposure group. Simultaneously, increased levels of glucose, triglyceride, alanine transaminase (ALT), aspartate transaminase (AST), superoxide dismutase, 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), interleukin-6, and lipid droplets were found in the 0.5 µm MP exposure group, while the fewer responses, including elevated liver weight index, glucose, high-density lipoprotein, AST, and decreased HNE-MA were observed in 5 µm MP exposure group. These results indicate that sub-chronic exposure to submicron MPs causes MP deposition in mouse livers, which further induces oxidative stress, increases inflammatory cytokines and perturbs glucose and lipid homeostasis, which might trigger more severe metabolic dysfunction or non-alcoholic steatohepatitis-like hepatotoxicity.
RESUMEN
Microplastics (MPs), emerging environmental toxicants, have drawn attention because of their wide distribution in the environment. Exposure to MPs induces gut microbiota dysbiosis, intestinal barrier dysfunction, metabolic perturbations, and neurotoxicity in different rodents. However, the relationship between MPs, gut microbiota, and the metabolome of the gut and brain in mice remains unclear. In this study, female C57BL/6 mice were orally gavaged with vehicle, 200 nm MP, and 800 nm MP three times per week for four weeks. Cecal contents were collected for gut microbiota analysis using 16S rRNA gene sequencing. Intestinal and brain tissues from mice were used to determine metabolic profiles using liquid chromatography-mass spectrometry (LC-MS). The results showed that MP altered microbiota composition, accompanied by metabolic perturbations in the mouse gut and brain. Specifically, Firmicutes and Bacteroidetes were suggested to be important phyla for MP exposure, partially dominating further metabolite alterations. Simultaneously, MP-induced metabolic profiles were associated with energy homeostasis and bile acid, nucleotide, and carnitine metabolic pathways. The results of the mediation analysis further revealed an MP-microbiota-metabolite relationship. Our results indicate that MPs can induce gut dysbiosis and disturb metabolic dysfunction in the mouse brain and/or intestine. Integrative omics approaches have the potential to monitor MP-induced molecular responses in various organs and systematically elucidate the complex mechanisms of human health effects.
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Microbiota , Plásticos , Ratones , Femenino , Humanos , Animales , Plásticos/toxicidad , Microplásticos/toxicidad , Disbiosis/inducido químicamente , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Ratones Endogámicos C57BL , Metaboloma , Encéfalo/metabolismoRESUMEN
Although microplastics (MPs) have become a global issue, the biodistribution and toxicities of MPs were still unclear. In this study, c57BL/6 mice were treated with submicron-sized MPs labeled with Nile red fluorescence by oral gavage three times a week for four consecutive weeks. Flow cytometry and microscopy technique were used to examine the concentration and distribution of MPs in various tissues and biofluids. The oxidative stress and inflammation were assessed via liquid chromatography-mass spectrometry and enzyme-linked immunosorbent assay, respectively. Submicron-sized MP signals were found in the intestines, liver, spleen, kidney, lungs, blood, and urine of mice after MP exposure. Increased oxidative stress in mouse urine and elevated inflammatory cytokines in mouse kidney were also recorded. In conclusion, flow cytometry is a useful tool for examining the number concentrations of MPs. Increased oxidative stress and inflammation after MP treatment indicates that the toxicity of MP warrants further investigation.
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Plásticos , Contaminantes Químicos del Agua , Ratones , Animales , Distribución Tisular , Microplásticos/toxicidad , Contaminantes Químicos del Agua/toxicidadRESUMEN
Background: [18F]FEPPA is a potent TSPO imaging agent that has been found to be a potential tracer for imaging neuroinflammation. In order to fulfill the demand of this tracer for preclinical and clinical studies, we have developed a one-pot automated synthesis with simplified HPLC purification of this tracer, which was then used for PET imaging of neuroinflammation in fine particulate matter- (PM2.5-) exposed rats. Results: Using this automated synthesis method, the RCY of the [18F]FEPPA was 38 ± 4% (n = 17, EOB) in a synthesis time of 83 ± 8 min from EOB. The radiochemical purity and molar activities were greater than 99% and 209 ± 138 GBq/µmol (EOS, n = 15), respectively. The quality of the [18F]FEPPA synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]FEPPA was stable at 21 ± 2°C for up to 4 hr after the end of synthesis (EOS). Moreover, microPET imaging showed that increased tracer activity of [18F]FEPPA in the brain of PM2.5-exposed rats (n = 6) were higher than that of normal controls (n = 6) and regional-specific. Conclusions: Using the improved semipreparative HPLC purification, [18F]FEPPA has been produced in high quantity, high quality, and high reproducibility and, for the first time, used for PET imaging the effects of PM2.5 in the rat brain. It is ready to be used for imaging inflammation in various clinical or preclinical studies, especially for nearby PET centers without cyclotrons.
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Enfermedades Neuroinflamatorias , Tomografía de Emisión de Positrones , Animales , Estudios de Factibilidad , Radioisótopos de Flúor , Material Particulado/toxicidad , Tomografía de Emisión de Positrones/métodos , Ratas , Reproducibilidad de los ResultadosRESUMEN
Fine particulate matter (PM2.5) poses a significant risk to human health. The molecular mechanisms underlying low-level PM2.5-induced neurotoxicity in the central nervous system remain unclear. In addition, changes in lipids in response to PM2.5 exposure have not yet been fully elucidated. In this study, 3xTg-Alzheimer's disease (AD) mice experienced continuous whole-body exposure to non-concentrated PM2.5 for three consecutive months, while control mice inhaled particulate matter-filtered air over the same time span. A liquid chromatography-mass spectrometry-based lipidomic platform was used to determine the distinct lipid profiles of various brain regions. The average PM2.5 concentration during the exposure was 11.38 µg/m3, which was close to the regulation limits of USA and Taiwan. The partial least squares discriminant analysis model showed distinct lipid profiles in the cortex, hippocampus, and olfactory bulb, but not the cerebellum, of mice in the exposure group. Increased levels of fatty acyls, glycerolipids, and sterol lipids, as well as the decreased levels of glycerophospholipids and sphingolipids in PM2.5-exposed mouse brains may be responsible for the increased energy demand, membrane conformation, neuronal loss, antioxidation, myelin function, and cellular signaling pathways associated with AD development. Our research suggests that subchronic exposure to low levels of PM2.5 may cause neurotoxicity by changing the lipid profiles in a susceptible model. Lipidomics is a powerful tool to study the early effects of PM2.5-induced AD toxicity.
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Contaminantes Atmosféricos , Enfermedad de Alzheimer , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Animales , Encéfalo , Exposición por Inhalación/efectos adversos , Exposición por Inhalación/análisis , Lipidómica , Lípidos/análisis , Ratones , Material Particulado/análisis , Material Particulado/toxicidadRESUMEN
BACKGROUND: Air pollution, especially fine particulate matter (PM), can cause brain damage, cognitive decline, and an increased risk of neurodegenerative disease, especially alzheimer's disease (AD). Typical pathological findings of amyloid and tau protein accumulation have been detected in the brain after exposure in animal studies. However, these observations were based on high levels of PM exposure, which were far from the WHO guidelines and those present in our environment. In addition, white matter involvement by air pollution has been less reported. Thus, this experiment was designed to simulate the true human world and to discuss the possible white matter pathology caused by air pollution. RESULTS: 6 month-old female 3xTg-AD mice were divided into exposure and control groups and housed in the Taipei Air Pollutant Exposure System (TAPES) for 5 months. The mice were subjected to the Morris water maze test after exposure and were then sacrificed with brain dissection for further analyses. The mean mass concentration of PM2.5 during the exposure period was 13.85 µg/m3. After exposure, there was no difference in spatial learning function between the two groups, but there was significant decay of memory in the exposure group. Significantly decreased total brain volume and more neuronal death in the cerebral and entorhinal cortex and demyelination of the corpus callosum were noted by histopathological staining after exposure. However, there was no difference in the accumulation of amyloid or tau on immunohistochemistry staining. For the protein analysis, amyloid was detected at significantly higher levels in the cerebral cortex, with lower expression of myelin basic protein in the white matter. A diffuse tensor image study also revealed insults in multiple white matter tracts, including the optic tract. CONCLUSIONS: In conclusion, this pilot study showed that even chronic exposure to low PM2.5 concentrations still caused brain damage, such as gross brain atrophy, cortical neuron damage, and multiple white matter tract damage. Typical amyloid cascade pathology did not appear prominently in the vulnerable brain region after exposure. These findings imply that multiple pathogenic pathways induce brain injury by air pollution, and the optic nerve may be another direct invasion route in addition to olfactory nerve.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Sustancia Blanca , Enfermedad de Alzheimer/inducido químicamente , Animales , Femenino , Ratones , Ratones Transgénicos , Enfermedades Neurodegenerativas/inducido químicamente , Enfermedades Neurodegenerativas/patología , Material Particulado/toxicidad , Proyectos Piloto , Sustancia Blanca/patologíaRESUMEN
Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer's disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM2.5 via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM2.5 for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM2.5 exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM2.5 induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM2.5 exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM2.5 subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM2.5 after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM2.5-mediated development of AD.
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Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/genética , Encéfalo/metabolismo , Material Particulado/toxicidad , Proteínas tau/genética , Contaminantes Atmosféricos/toxicidad , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Cromatografía Liquida , Cognición/fisiología , Modelos Animales de Enfermedad , Hipocampo/diagnóstico por imagen , Hipocampo/efectos de los fármacos , Hipocampo/patología , Exposición por Inhalación/efectos adversos , Imagen por Resonancia Magnética , Malondialdehído/metabolismo , Espectrometría de Masas , Ratones , Ratones Transgénicos , Neuronas/metabolismo , Neuronas/patología , Bulbo Olfatorio/metabolismo , Bulbo Olfatorio/patología , Estrés Oxidativo/genética , Tamaño de la PartículaRESUMEN
Fine particulate matter (PM2.5) is able to pass through the respiratory barrier to enter the circulatory system and can consequently spread to the whole body to cause toxicity. Although our previous studies have revealed significantly altered levels of phosphorylcholine-containing lipids in the lungs of rats after chronic inhalation exposure to PM2.5, the effects of PM2.5 on phosphorylcholine-containing lipids in the extrapulmonary organs have not yet been elucidated. In this study, we examined the lipid effects of chronic PM2.5 exposure on various organs and serum by using a rat inhalation model followed by a mass spectrometry-based lipidomic approach. Male Sprague-Dawley rats were continuously exposed at the whole body level to nonfiltered and nonconcentrated ambient air from the outside environment of Taipei city for 8 months, while the control rats inhaled filtered air simultaneously. After exposure, serum samples and various organs, including the testis, pancreas, heart, liver, kidney, spleen, and epididymis, were collected for lipid extraction and analysis to examine the changes in phosphorylcholine-containing lipids after exposure. The results from the partial least squares discriminant analysis models demonstrated that the lipid profiles in the PM2.5 exposure group were different from those in the control group in the rat testis, pancreas, heart, liver, kidney and serum. The greatest PM2.5-induced lipid effects were observed in the testes. Decreased lyso-phosphatidylcholines (PCs) as well as increased unsaturated diacyl-PCs and sphingomyelins in the testes may be related to maintaining the membrane integrity of spermatozoa, antioxidation, and cell signaling. Additionally, our results showed that decreased PC(16:0/18:1) was observed in both the serum and testes. In conclusion, exposure to chronic environmental concentrations of PM2.5 caused lipid perturbation, especially in the testes of rats. This study highlighted the susceptibility of the testes and suggested possible molecular events for future study.
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Contaminantes Atmosféricos , Material Particulado , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Animales , Ciudades , Lípidos/análisis , Masculino , Material Particulado/análisis , Material Particulado/toxicidad , Ratas , Ratas Sprague-DawleyRESUMEN
Particle morphology can affect the performance of an electrostatic precipitator air-liquid interface (ESP-ALI) cell exposure system and the resulting cell toxicity. In this study, three types of monodisperse aerosols - spherical sucrose particles, nonspherical align soot aggregates, and nanosilver aggregates/agglomerates - were selected to evaluate the collection efficiency at flow rates ranging from 0.3 to 1.5 lpm. To quantify the particle morphology, the fractal dimensions (Df) of the tested aerosols were characterized. The penetration of fine particles (dp = 100-250 nm) under different operating conditions was correlated with a characteristic exponential curve using the dimensionless drift velocity (Vc/Vavg,r) as the scaling parameter. For nanoparticles (NPs, dp <100 nm) with different particle morphologies, the particle penetrations in the ESP-ALI were similar, but their diffusion losses were not negligible. In contrast, for fine particles, the collection efficiency of soot nanoaggregates (Df = 2.29) was higher than that of spherical sucrose particles. This difference might be due to the simultaneous influences of the electric field-induced and flow field-induced alignment. Furthermore, based on Zhibin and Guoquan's Deutsch model, a quadratic equation was applied to fit the experimental data and to predict the performance of the ESP-ALI.
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Nanopartículas , Electricidad Estática , Aerosoles/toxicidad , Contaminantes Atmosféricos/análisis , Nanopartículas/toxicidad , Tamaño de la PartículaRESUMEN
BACKGROUND: Epidemiological evidence has linked fine particulate matter (PM2.5) to neurodegenerative diseases; however, the toxicological evidence remains unclear. The objective of this study was to investigate the effects of PM2.5 on neuropathophysiology in a hypertensive animal model. We examined behavioral alterations (Morris water maze), lipid peroxidation (malondialdehyde (MDA)), tau and autophagy expressions, neuron death, and caspase-3 levels after 3 and 6 months of whole-body exposure to urban PM2.5 in spontaneously hypertensive (SH) rats. RESULTS: SH rats were exposed to S-, K-, Si-, and Fe-dominated PM2.5 at 8.6 ± 2.5 and 10.8 ± 3.8 µg/m3 for 3 and 6 months, respectively. We observed no significant alterations in the escape latency, distance moved, mean area crossing, mean time spent, or mean swimming velocity after PM2.5 exposure. Notably, levels of MDA had significantly increased in the olfactory bulb, hippocampus, and cortex after 6 months of PM2.5 exposure (p < 0.05). We observed that 3 months of exposure to PM2.5 caused significantly higher expressions of t-tau and p-tau in the olfactory bulb (p < 0.05) but not in other brain regions. Beclin 1 was overexpressed in the hippocampus with 3 months of PM2.5 exposure, but significantly decreased in the cortex with 6 months exposure to PM2.5. Neuron numbers had decreased with caspase-3 activation in the cerebellum, hippocampus, and cortex after 6 months of PM2.5 exposure. CONCLUSIONS: Chronic exposure to low-level PM2.5 could accelerate the development of neurodegenerative pathologies in subjects with hypertension.
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Contaminantes Atmosféricos/toxicidad , Material Particulado/toxicidad , Animales , Encéfalo/efectos de los fármacos , Femenino , Hipocampo/efectos de los fármacos , Exposición por Inhalación , Masculino , Neuropatología , Tamaño de la Partícula , Ratas , Ratas Endogámicas SHRRESUMEN
Reducing nosocomial transmission within health care facilities is important, but the number of negative-pressure airborne infection isolation rooms for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is limited. It is a daunting challenge to cope with a surge of suspected infectious patients in hospitals. We installed air exhaust fans on the windows to change the pressure direction within the wards rapidly. The best location for the fans was 90 cm from the floor and 90 cm from the edge of bed whether the indoor air conditioners were on or off. The noise level should be <60 dB(A) as per government regulations. General wards can be transformed into makeshift negative-pressure rooms easily and effectively within 24 hours, which is really the simple, fast, and effective way for the transformation being applied.
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Unidades de Observación Clínica/organización & administración , Infecciones por Coronavirus/prevención & control , Infección Hospitalaria/prevención & control , Pandemias/prevención & control , Aislamiento de Pacientes , Neumonía Viral/prevención & control , Ventilación/métodos , COVID-19 , Infecciones por Coronavirus/epidemiología , Humanos , Neumonía Viral/epidemiología , Taiwán/epidemiologíaRESUMEN
Recent studies have illustrated an association between ambient fine particulate matter (PM2.5) exposure and neuronal toxicity in epidemiological studies and animal models. However, the possible molecular effects on brains under real-world exposure to PM2.5 remain unclear. In this pilot study, male spontaneously hypertensive rats were whole-bodily exposed to ambient air from the outdoor environment of Taipei City for 3 months, while the control rats inhaled HEPA-filtered air. The PM2.5-induced phosphatidylcholine and sphingomyelin profiles in the hippocampus, cortex, medulla, cerebellum, and olfactory bulb were assessed by mass spectrometry (MS)-based lipidomics. Partial least squares discriminant analysis (PLS-DA) and the Wilcoxon rank sum test were used to examine the lipid changes between the exposed and control groups. The PLS-DA models showed that phosphatidylcholine and sphingomyelin profiles of the PM2.5 exposure group were different from those of the control group in each brain region except the cortex. More lipid changes were found in the hippocampus, while fewer lipid changes were observed in the olfactory bulb. The lipid alteration in the hippocampus may strengthen membrane integrity, modulate signaling pathways, and avoid accumulation of lipofuscin to counter the PM2.5-induced stress. The lipid changes in the cortex and medulla may respond to PM2.5-induced injury and inflammation; while the lipid changes in the cerebellum were associated with neuron protection. This study suggests that the MS-based lipidomics is a powerful approach to discriminate the brain lipid profiles even at the environmental level of ambient PM2.5 and has the potential to suggest possible adverse health effects in long-term PM2.5 exposure studies.
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Encéfalo , Contaminantes Atmosféricos , Animales , Ciudades , Exposición a Riesgos Ambientales , Lípidos , Masculino , Material Particulado , Proyectos Piloto , Ratas , Ratas Endogámicas SHRRESUMEN
Zinc oxide nanoparticles (ZnONPs) are widely used in the manufacturing of many commercial products. Workers exposed to ZnO particles may develop metal fume fever. Our previous study suggested that the oropharyngeal aspiration of ZnONPs could cause eosinophilic airway inflammation and increase T helper 2 (Th2) cytokine expression in the absence of allergens in mice. ZnO has been used topically as a sunscreen and a therapeutic agent for dermatological conditions. To understand whether inhalation and topically applied ZnONPs might cause or exert an adjuvant effect on the development of allergic airway inflammation in mice, C57BL/6â¯J mice were exposed to filtered air or 2.5â¯mg/m3 ZnONPs via whole-body inhalation for 5â¯h a day over 5â¯days, and BALB/c mice were topically exposed to ZnONPs using modified mouse models of atopic dermatitis (AD) and asthma. Ovalbumin (OVA) solution was used as an allergen in the topical exposure experiments. A significantly increased eosinophil count and mixed Th1/Th2 cytokine expression were detected in the bronchoalveolar lavage fluid (BALF) after ZnONP inhalation. However, only mild eosinophilia and low Th2 cytokine expression were detected in the BALF after oropharyngeal OVA aspiration in the high-dose ZnONP topical treatment group. These results suggest that ZnONP inhalation might play a role in the development of allergic airway inflammation in mice. However, topically applied ZnONPs only play a limited role in the development of allergic airway inflammation in mice.
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Asma/inducido químicamente , Dermatitis Atópica/inducido químicamente , Eosinofilia/inducido químicamente , Nanopartículas del Metal/toxicidad , Óxido de Zinc/toxicidad , Administración por Inhalación , Administración Tópica , Animales , Asma/diagnóstico , Asma/inmunología , Líquido del Lavado Bronquioalveolar/citología , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/inmunología , Modelos Animales de Enfermedad , Eosinofilia/diagnóstico , Eosinofilia/inmunología , Femenino , Humanos , Exposición por Inhalación/efectos adversos , Nanopartículas del Metal/administración & dosificación , Ratones , Óxido de Zinc/administración & dosificaciónRESUMEN
Neurotoxicity caused by particulate matter (PM) has been highlighted as being a potential risk factor for neurodegenerative diseases. However, the effects of brain inflammation in response to traffic-related PM remain unclear. The objective of this study was to investigate the effects of traffic-related PM on microglial responses. We determined the cytotoxicity, oxidative stress, lipid peroxidation, inflammation, activation, autophagy, and apoptosis due to exposure to carbon black (CB) and diesel exhaust particles (DEPs) in Bv2 microglial cells. Additionally, cells were pretreated with corticosteroid to determine alterations in microglial activation and inflammation. For in vivo confirmation, Sprague Dawley (SD) rats were whole-body exposed to traffic-related PM1 (PM with an aerodynamic diameter of <1⯵m) for 3 and 6 months. We observed that a decrease in cell viability and increases in dichlorodihydrofluorescein (DCFH), lactate dehydrogenase (LDH), and thiobarbituric acid-reactive substances (TBARSs) occurred due to CB and DEP. Production of interleukin (IL)-6 and soluble tumor necrosis factor (TNF)-α was significantly stimulated by CB and DEP, whereas production of cellular TNF-α was significantly stimulated by CB. Iba1 and prostaglandin E2 (PGE2) significantly increased due to CB and DEP. Consistently, we observed significant increases in Iba1 in the hippocampus of rats after 3 and 6 months of exposure to traffic-related PM1. We found that the light chain 3II (LC3II)/LC3I ratio and caspase-3 activity increased due to CB and DEP exposure. Subsequently, LDH, TBARS, LC3II/I, and caspase-3 activities did not clearly respond to corticosteroid pretreatment followed by DEP exposure in BV2 cells. Results of the present study suggested that traffic-related PM induced cytotoxicity, lipid peroxidation, microglial activation, and inflammation as well as autophagy and caspase-3 regulation in microglia. We demonstrated that microglial activation and inflammation may play important roles in the response of the brain to traffic-related PM.
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Inflamación/etiología , Microglía/efectos de los fármacos , Material Particulado/toxicidad , Animales , Autofagia/efectos de los fármacos , Encéfalo/patología , Proteínas de Unión al Calcio/análisis , Línea Celular , Supervivencia Celular/efectos de los fármacos , Dinoprostona/análisis , Interleucina-6/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Masculino , Proteínas de Microfilamentos/análisis , Microglía/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Emisiones de Vehículos/toxicidadRESUMEN
After the publication of this article [1] it was hihglighted that the number of deaths related to natural disasters was incorrectly reported in the second paragraph of the Hazards from Natural particulates and the evolution of the biosphere section. This correction article shows the correct and incorrect statement. This correction does not change the idea presented in the article that from an evolutionary view point, natural disasters account only for a small fraction of the people on the planet. The original article has been updated.
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BACKGROUND: Particles and fibres affect human health as a function of their properties such as chemical composition, size and shape but also depending on complex interactions in an organism that occur at various levels between particle uptake and target organ responses. While particulate pollution is one of the leading contributors to the global burden of disease, particles are also increasingly used for medical purposes. Over the past decades we have gained considerable experience in how particle properties and particle-bio interactions are linked to human health. This insight is useful for improved risk management in the case of unwanted health effects but also for developing novel medical therapies. The concepts that help us better understand particles' and fibres' risks include the fate of particles in the body; exposure, dosimetry and dose-metrics and the 5 Bs: bioavailability, biopersistence, bioprocessing, biomodification and bioclearance of (nano)particles. This includes the role of the biomolecule corona, immunity and systemic responses, non-specific effects in the lungs and other body parts, particle effects and the developing body, and the link from the natural environment to human health. The importance of these different concepts for the human health risk depends not only on the properties of the particles and fibres, but is also strongly influenced by production, use and disposal scenarios. CONCLUSIONS: Lessons learned from the past can prove helpful for the future of the field, notably for understanding novel particles and fibres and for defining appropriate risk management and governance approaches.
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Contaminantes Atmosféricos/toxicidad , Exposición por Inhalación/efectos adversos , Fibras Minerales/toxicidad , Nanopartículas/toxicidad , Material Particulado/toxicidad , Contaminantes Atmosféricos/química , Humanos , Nanopartículas/química , Tamaño de la Partícula , Material Particulado/química , Medición de Riesgo , Gestión de Riesgos , Propiedades de SuperficieRESUMEN
BACKGROUND: Effects of air pollution on neurotoxicity and behavioral alterations have been reported. The objective of this study was to investigate the pathophysiology caused by particulate matter (PM) in the brain. We examined the effects of traffic-related particulate matter with an aerodynamic diameter of < 1 µm (PM1), high-efficiency particulate air (HEPA)-filtered air, and clean air on the brain structure, behavioral changes, brainwaves, and bioreactivity of the brain (cortex, cerebellum, and hippocampus), olfactory bulb, and serum after 3 and 6 months of whole-body exposure in 6-month-old Sprague Dawley rats. RESULTS: The rats were exposed to 16.3 ± 8.2 (4.7~ 68.8) µg/m3 of PM1 during the study period. An MRI analysis showed that whole-brain and hippocampal volumes increased with 3 and 6 months of PM1 exposure. A short-term memory deficiency occurred with 3 months of exposure to PM1 as determined by a novel object recognition (NOR) task, but there were no significant changes in motor functions. There were no changes in frequency bands or multiscale entropy of brainwaves. Exposure to 3 months of PM1 increased 8-isoporstance in the cortex, cerebellum, and hippocampus as well as hippocampal inflammation (interleukin (IL)-6), but not in the olfactory bulb. Systemic CCL11 (at 3 and 6 months) and IL-4 (at 6 months) increased after PM1 exposure. Light chain 3 (LC3) expression increased in the hippocampus after 6 months of exposure. Spongiosis and neuronal shrinkage were observed in the cortex, cerebellum, and hippocampus (neuronal shrinkage) after exposure to air pollution. Additionally, microabscesses were observed in the cortex after 6 months of PM1 exposure. CONCLUSIONS: Our study first observed cerebral edema and brain impairment in adult rats after chronic exposure to traffic-related air pollution.
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Contaminantes Atmosféricos/toxicidad , Encéfalo/efectos de los fármacos , Exposición por Inhalación/efectos adversos , Material Particulado/toxicidad , Contaminación por Tráfico Vehicular/efectos adversos , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Edema Encefálico/inducido químicamente , Electroencefalografía , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo/efectos de los fármacos , Ratas Sprague-Dawley , Prueba de Desempeño de Rotación con Aceleración ConstanteRESUMEN
Zinc oxide (ZnO) nano- and fine-sized particles are associated with respiratory toxicity in humans, but the underlying molecular mechanisms remain unclear. Our previous nuclear magnetic resonance-based metabolomic study demonstrated that changes in phosphorylcholine-containing lipids (PC-CLs) in the respiratory system were associated with ZnO particle-induced respiratory toxicity. However, the details of the lipid species associated with adverse effects and possible biomarker signatures have not been identified. Thus, a liquid chromatography-mass spectrometry (LC-MS)-based lipidomics platform was applied to examine the alterations of PC-CL species in the lungs of rats treated with a series of concentrations of nano-sized (35 nm) or fine-sized (250 nm) ZnO particles via inhalation. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and the Mann-Whitney U (MWU) test with false discovery rate (FDR) control were conducted to explore the perturbed lipid species and to discriminate a potential pulmonary biomarker signature after ZnO particle exposure. The PCA and PLS-DA models revealed that the fine-sized ZnO particle-treated groups and the high-concentration nano-sized group were separated from the control groups as well as from the low and moderate nano-sized groups. The results from the MWU test further suggested that after FDR adjustment, numerous PC-CL species were altered in the high-concentration and moderate-concentration fine-sized groups. Furthermore, our results suggested that lipids involved in anti-oxidation, membrane conformation, and cellular signal transduction were altered in response to ZnO-induced oxidative stress and inflammation. One lipid, PC(18:0/18:1), exhibited good performance (AUC > 0.8) of discriminative ability in distinguishing ZnO particle exposure from the control. These findings not only provide a foundation for the exploration of possible ZnO particle-mediated mechanisms but also suggest a lipid biomarker for ZnO particle exposure.
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Lípidos/análisis , Pulmón/efectos de los fármacos , Metabolómica , Nanopartículas/toxicidad , Óxido de Zinc/toxicidad , Animales , Cromatografía Liquida , Humanos , Exposición por Inhalación , Pulmón/química , Masculino , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en TándemRESUMEN
The association between short-term exposure to particulate air pollution, especially fine particles, and cardiopulmonary health has been well-established in previous studies. However, previous findings regarding the effect of ultrafine particles (UFPs) on cardiopulmonary health are inconsistent. We repeatedly measured the mass concentrations of UFPs using a Micro-Orifice Uniform Deposit Impactor (MOUDI) in the apartments of 100 adult participants and collected the participants' health data from the pulmonary outpatient unit of Shuang-Ho Hospital to investigate the association between short-term exposure to UFPs and cardiopulmonary health using mixed-effects models from January 1, 2014 to August 31, 2017. We also collected ambient air pollution monitoring data from the Taiwan Environmental Protection Administration for data analysis. We observed that an interquartile range increase in the 24-hour mean UFPs (0.97⯵g/m3) was associated with a 6.3% [95% confidence interval (CI)â¯=â¯2.9, 9.7], 5.6% (95% CIâ¯=â¯4.1, 7.1) and 8.5% (95% CIâ¯=â¯3.9, 13.1) increase in systolic blood pressure, diastolic blood pressure and high sensitivity-C-reactive protein, respectively. We also observed the association of particulate matter less than or equal to 2.5⯵m in diameter and nitrogen dioxide with increased blood pressure and ozone with decreased lung function. A negative trend between UFPs and forced expiratory volume in the first second was observed. We concluded that short-term exposure to UFPs was associated with cardiovascular health in adult subjects in the urban areas of northern Taiwan.