Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 83
Filtrar
1.
Exp Lung Res ; 46(3-4): 64-74, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32067522

RESUMEN

Purpose: Aluminum is the third most abundant metal in the earth's crust and is widely used in industry. Chronic contact with aluminum results in a reduction in the activity of electron transport chain complexes, leading to excessive production of reactive oxygen species (ROS) and oxidative stress. This study aimed to evaluate the effects of short-term exposure of aluminum hydroxide on oxidative stress and pulmonary inflammatory response.Materials and methods: Male BALB/c mice were divided into three groups: control group (CG); phosphate buffered saline group (PBSG) and aluminum hydroxide group (AHG). CG was exposed to ambient air, while PBSG and AHG were exposed to PBS or aluminum hydroxide solutions via nebulization, three times per day for five consecutive days. Twenty-four hours after the last exposure, all animals were euthanized for subsequent analysis.Results: Exposure to aluminum hydroxide in the blood resulted in lower platelet levels, higher neutrophils, and lower monocytes compared to CG and PBSG. Aluminum hydroxide promoted the recruitment of inflammatory cells to the lung. Macrophage, neutrophil and lymphocyte counts were higher in AHG compared to CG and PBSG. Protein oxidation and superoxide dismutase activity were higher, while catalase activity and reduced and oxidizes glutathione ratio in AHG were lower compared to CG and PBSG. Furthermore, there was an increase in the inflammatory markers CCL2 and IFN-γ in AHG compared to CG and PBSG.Conclusion: In conclusion, short-term nebulization with aluminum hydroxide induces the influx of inflammatory cells and oxidative stress in adult BALB/c mice.


Asunto(s)
Hidróxido de Aluminio/toxicidad , Exposición por Inhalación/efectos adversos , Pulmón/efectos de los fármacos , Exposición Profesional/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Animales , Masculino , Ratones Endogámicos BALB C , Nanopartículas/efectos adversos , Distribución Aleatoria
2.
Ecotoxicol Environ Saf ; 145: 359-366, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28759765

RESUMEN

The objective of this study was to examine the impact of aluminium on the perennial macroalgae Chara hispida L. and its bioaccumulation capacities. Aluminium (Al) was introduced into the environment in the form of polyaluminium chloride, an agent utilized in the restoration of waterbodies. Research was conducted in an experimental setting using mesocosms (volume 0.8m3) placed in the littoral zone of a lake with C. hispida. Three doses of the coagulant were applied, each with a different volume: low - 6.1g Al m-3, medium - 12.2gm-3 and high - 24.5g Al m-3. A significant acidification of environment was determined, which would imply the presence of toxic Al3+ ions. It has been demonstrated that aluminium penetrates and accumulates in the cells of the charophyte. This caused damage to the thalli, which manifested itself in chloroses, necroses, flaking of the cortex cells and softening of the thallus, whose severity was proportionate to the dose of the coagulant. The first negative signs were observed after 24h. The study shows that C. hispida is a poor accumulator of aluminium (bioconcentration factor < 200), while bioaccumulation capacity was inhibited at the concentration of approx. 2.0mg Al g-1 d.w. Accumulation in the thalli of the charophytes accounted for 58% of variation following removal of aluminium from the environment. The results of the experiment demonstrate a negative impact of aluminium on charophytes at concentrations used in aggressive restoration of lakes.


Asunto(s)
Hidróxido de Aluminio/toxicidad , Chara/efectos de los fármacos , Lagos/química , Algas Marinas/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Biodegradación Ambiental , Chara/metabolismo , Algas Marinas/metabolismo
3.
J Appl Toxicol ; 36(3): 424-33, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26437923

RESUMEN

With the rapid development of the nano-industry, concerns about their potential adverse health effects have been raised. Thus, ranking accurately their toxicity and prioritizing for in vivo testing through in vitro toxicity test is needed. In this study, we used three types of synthesized aluminum oxide nanoparticles (AlONPs): γ-aluminum oxide hydroxide nanoparticles (γ-AlOHNPs), γ- and α-AlONPs. All three AlONPs were spherical, and the surface area was the greatest for γ-AlONPs, followed by the α-AlONPs and γ-AlOHNPs. In mice, γ-AlOHNPs accumulated the most 24 h after a single oral dose. Additionally, the decreased number of white blood cells (WBC), the increased ratio of neutrophils and the enhanced secretion of interleukin (IL)-8 were observed in the blood of mice dosed with γ-AlOHNPs (10 mg kg(-1)). We also compared their toxicity using four different in vitro test methods using six cell lines, which were derived from their potential target organs, BEAS-2B (lung), Chang (liver), HACAT (skin), H9C2 (heart), T98G (brain) and HEK-293 (kidney). The results showed γ-AlOHNPs induced the greatest toxicity. Moreover, separation of particles was observed in a transmission electron microscope (TEM) image of cells treated with γ-AlOHNPs, but not γ-AlONPs or α-AlONPs. In conclusion, our results suggest that the accumulation and toxicity of AlONPs are stronger in γ-AlOHNPs compared with γ-AlONPs and α-AlONPs owing their low stability within biological system, and the presence of hydroxyl group may be an important factor in determining the distribution and toxicity of spherical AlONPs.


Asunto(s)
Hidróxido de Aluminio/toxicidad , Óxido de Aluminio/toxicidad , Nanopartículas del Metal/toxicidad , Adenosina Trifosfato/metabolismo , Administración Oral , Hidróxido de Aluminio/metabolismo , Óxido de Aluminio/metabolismo , Animales , Bioensayo , Biomarcadores/sangre , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/ultraestructura , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células HEK293 , Humanos , Interleucina-8/sangre , Riñón/efectos de los fármacos , Riñón/ultraestructura , L-Lactato Deshidrogenasa/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/ultraestructura , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/ultraestructura , Masculino , Ratones Endogámicos ICR , Microscopía Electrónica de Transmisión , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/ultraestructura , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/metabolismo , Tamaño de la Partícula , Ratas , Medición de Riesgo , Piel/efectos de los fármacos , Piel/metabolismo , Piel/ultraestructura , Propiedades de Superficie , Factores de Tiempo , Distribución Tisular
4.
Int J Toxicol ; 35(3 suppl): 16S-33S, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27913785

RESUMEN

This is a safety assessment of alumina and aluminum hydroxide as used in cosmetics. Alumina functions as an abrasive, absorbent, anticaking agent, bulking agent, and opacifying agent. Aluminum hydroxide functions as a buffering agent, corrosion inhibitor, and pH adjuster. The Food and Drug Administration (FDA) evaluated the safe use of alumina in several medical devices and aluminum hydroxide in over-the-counter drugs, which included a review of human and animal safety data. The Cosmetic Ingredient Review (CIR) Expert Panel considered the FDA evaluations as part of the basis for determining the safety of these ingredients as used in cosmetics. Alumina used in cosmetics is essentially the same as that used in medical devices. This safety assessment does not include metallic or elemental aluminum as a cosmetic ingredient. The CIR Expert Panel concluded that alumina and aluminum hydroxide are safe in the present practices of use and concentration described in this safety assessment.


Asunto(s)
Hidróxido de Aluminio/toxicidad , Óxido de Aluminio/toxicidad , Seguridad de Productos para el Consumidor , Cosméticos/normas , Hidróxido de Aluminio/análisis , Hidróxido de Aluminio/farmacocinética , Óxido de Aluminio/análisis , Óxido de Aluminio/farmacocinética , Animales , Seguridad de Productos para el Consumidor/legislación & jurisprudencia , Cosméticos/química , Equipos y Suministros/normas , Regulación Gubernamental , Humanos , Estructura Molecular , Pruebas de Toxicidad/métodos , Toxicocinética , Estados Unidos , United States Food and Drug Administration
5.
J Appl Toxicol ; 35(12): 1577-85, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25752809

RESUMEN

The human papillomavirus (HPV)-16/18 vaccine (Cervarix®) is a prophylactic vaccine for the prevention of cervical cancer. The vaccine contains recombinant virus-like particles assembled from the L1 major capsid proteins of the cervical cancer-causing viral types HPV-16 and HPV-18, and Adjuvant System 04 (AS04), which contains the immunostimulant MPL and aluminium salt. To evaluate potential local and systemic toxic effects of the HPV-16/18 vaccine or AS04 alone, three repeated-dose studies were performed in rabbits and rats. One rabbit study also included a single-dose evaluation. In rabbits (~2.5 kg), the full human dose (HD) of the vaccine was evaluated (0.5 ml per injection site), and in rats (~250 g), 1/5 HD of vaccine was evaluated, corresponding to ≥ 12 times the dosage in humans relative to body weight. In both animal models, the treatment-related changes included a slight transient increase in the number of circulating neutrophils as well as a local inflammatory reaction at the injection site. These treatment-related changes were less pronounced after four doses of AS04 alone than after four doses of the HPV-16/18 vaccine. Additional treatment-related changes in the rat included lower albumin/globulin ratios and microscopic signs of inflammation in the popliteal lymph nodes. In both animal models, 13 weeks after the fourth dose, recovery was nearly complete, although at the injection site in some animals there were signs of discoloration, muscle-fibre regeneration and focal points of macrophage infiltration. Therefore, in these non-clinical models, the single and repeated dose administrations of the HPV-16/18 vaccine or AS04 alone were safe and well tolerated.


Asunto(s)
Hidróxido de Aluminio/toxicidad , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Lípido A/análogos & derivados , Vacunas contra Papillomavirus/toxicidad , Hidróxido de Aluminio/administración & dosificación , Hidróxido de Aluminio/inmunología , Animales , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Femenino , Inyecciones Intramusculares , Lípido A/administración & dosificación , Lípido A/inmunología , Lípido A/toxicidad , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Vacunas contra Papillomavirus/inmunología , Conejos , Ratas , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/prevención & control
6.
Crit Rev Toxicol ; 44 Suppl 4: 1-80, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25233067

RESUMEN

Abstract Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007) . Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of "total Al"assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al(+3) to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)(+2) and Al(H2O)6 (+3)] that after complexation with O2(•-), generate Al superoxides [Al(O2(•))](H2O5)](+2). Semireduced AlO2(•) radicals deplete mitochondrial Fe and promote generation of H2O2, O2 (•-) and OH(•). Thus, it is the Al(+3)-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer's disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances.


Asunto(s)
Hidróxido de Aluminio/toxicidad , Óxido de Aluminio/toxicidad , Aluminio/toxicidad , Nanopartículas/toxicidad , Exposición Profesional/efectos adversos , Animales , Carcinogénesis/efectos de los fármacos , Sistema Cardiovascular/efectos de los fármacos , Sistema Nervioso Central/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Sistema Endocrino/efectos de los fármacos , Europa (Continente) , Tracto Gastrointestinal/efectos de los fármacos , Guías como Asunto/normas , Humanos , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Sistema Respiratorio/efectos de los fármacos , Medición de Riesgo , Factores de Riesgo
7.
Inhal Toxicol ; 26(9): 545-53, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24992651

RESUMEN

Boehmite (γ-AlOOH) nanoparticles (NPs) are used in a wide range of industrial applications. However, little is known about their potential toxicity. This study aimed at a better understanding of the relationship between the physico-chemical properties of these NPs and their in vitro biological activity. After an extensive physico-chemical characterization, the cytotoxicity, pro-inflammatory response and oxidative stress induced by a bulk industrial powder and its ultrafine fraction were assessed using RAW264.7 macrophages. Although the bulk powder did not trigger a significant biological activity, pro-inflammatory response was highly enhanced with the ultrafine fraction. This observation was confirmed with boehmite NPs synthesized at the laboratory scale, with well-defined and tightly controlled physico-chemical features: toxicity was increased when NPs were dispersed. In conclusion, the agglomerates size of boehmite NPs has a major impact on their toxicity, highlighting the need to study not only raw industrial powders containing NPs but also the ultrafine fractions representative of respirable particles.


Asunto(s)
Hidróxido de Aluminio/toxicidad , Óxido de Aluminio/toxicidad , Macrófagos/efectos de los fármacos , Nanopartículas/química , Hidróxido de Aluminio/química , Óxido de Aluminio/química , Animales , Línea Celular , Fenómenos Químicos , Inflamación , Macrófagos/citología , Ratones , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , Pruebas de Toxicidad
8.
J Environ Manage ; 139: 146-53, 2014 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-24685456

RESUMEN

Four iron and aluminium-based products, including red mud (RM), hematite (Fe2O3), an iron-rich water treatment residual (Fe-WTR) and amorphous Al hydroxide (Al-OH), were evaluated for their effectiveness at stabilising As and heavy metals (i.e. Cd, Cu, Pb, Zn) in a circumneutral contaminated soil [As (2105 mg kg(-1)), Cd (18 mg kg(-1)), Cu (264 mg kg(-1)), Pb (710 mg kg(-1)), Zn (522 mg kg(-1))]. Treatment impacts on soil microbial and biochemical features (i.e. microbial biomass-C, microbial counts, 16S rRNA PCR-TTGE of culturable bacteria, dehydrogenase, urease and ß-glucosidase activity, Biolog derived parameters-AWCD and richness) as well as bean (Phaseolus vulgaris) and wheat (Triticum vulgare) growth were also assessed. After 6 months equilibration, all the amendments (application rate 3% w/w) but RM reduced labile As while only Al-OH reduced the concentration of water-soluble heavy metals. Despite the highest bioavailability of contaminants, most of the soil microbial and biochemical features monitored (i.e. microbial biomass-C, total bacterial counts, dehydrogenase activity and AWCD) were significantly higher in the RM-soil. Bean germination was completely inhibited in RM-soil while wheat growth was similar to that of the control. The Al-OH treatment was best overall, promoting microbial abundance, diversity and activity while increasing bean and wheat growth and reducing As accumulated in plant shoots. Results suggest that Al-OH is a suitable candidate for field evaluations while the use of RM in the remediation of circumneutral or subalkaline contaminated soils should be reconsidered.


Asunto(s)
Hidróxido de Aluminio/química , Arsénico/química , Compuestos Férricos/química , Hierro/química , Metales Pesados/química , Contaminantes del Suelo/química , Hidróxido de Aluminio/toxicidad , Carga Bacteriana , Biomasa , Compuestos Férricos/toxicidad , Hierro/toxicidad , Phaseolus/efectos de los fármacos , Phaseolus/crecimiento & desarrollo , ARN Ribosómico 16S/análisis , Microbiología del Suelo , Triticum/efectos de los fármacos , Triticum/crecimiento & desarrollo
9.
Arch Razi Inst ; 77(1): 221-228, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35891766

RESUMEN

Aluminum hydroxide nanoparticles have been employed in many industries, which are widely abundant in many aspects of human life. The role of the aluminum hydroxide nanoparticles adjuvant is to enhance the immune response. However, the impact of nanoparticles exposure has not been perfectly investigated yet. Accordingly, some questions have been raised about their potentially harmful effects, based on which the current research aims to answer them. This study aimed to investigate the histological effects of aluminum hydroxide nanoparticles and bulk-aluminum hydroxide (bulk Al[OH]3) on the liver, lung, heart, and kidney tissues. For this reason, an experiment was implemented on the aluminum hydroxide nanoparticles adjuvant in five neonatal mice. Intramuscularly, the mice were injected with 0.125 mL of adjuvanted vaccine, while five neonatal mice were injected with bulk and nanoparticles of Al (OH)3 and then sacrificed after one and two months, respectively. Vaccines were controlled by evaluating the histopathological response in neonatal mice. Subsequently, the pathological effect of both adjuvants was surveyed using the histological study of the lung, liver, heart, and kidney of the animals. The obtained recorded data indicated that both types of vaccine adjuvants caused pathological lesions on the histology sections of the liver, lung, heart, and kidney tissues. Moreover, bulk Al (OH)3 adjuvant vaccine was more effective and had a higher pathological response than aluminum hydroxide nanoparticles adjuvant vaccine. In addition, the total DNA content in both groups was estimated using Fluorometer from Promega. Compared to aluminum hydroxide nanoparticles groups, the tissues indicated a decrease in total DNA content obtained in bulk Al (OH)3 groups. Therefore, it can be concluded that the exposure to aluminum hydroxide nanoparticles would result in less pronounced toxicity, as well as systemic inflammation, compared to the bulk Al (OH)3 aluminum hydroxide.


Asunto(s)
Nanopartículas , Vacunas , Adyuvantes Inmunológicos/toxicidad , Hidróxido de Aluminio/toxicidad , Animales , Animales Recién Nacidos , ADN , Ratones , Nanopartículas/toxicidad
10.
Environ Health Prev Med ; 16(1): 16-24, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21432213

RESUMEN

OBJECTIVES: Aluminum is notorious as a neurotoxic metal. The aim of our study was to determine whether endoplasmic reticulum (ER) stress is involved in aluminum-induced apoptosis in astrocytes. METHODS: Mitochondrial RNA (mRNA) was analyzed by reverse transcription (RT)-PCR following pulse exposure of aluminum glycinate to primary cultured astrocytes. Tunicamycin was used as a positive control. RESULTS: Gene expression analysis revealed that Ire1ß was up-regulated in astrocytes exposed to aluminum while Ire1α was up-regulated by tunicamycin. Exposure to aluminum glycinate, in contrast to tunicamycin, seemed to down-regulate mRNA expression of many genes, including the ER resident molecular chaperone BiP/Grp78 and Ca(2+)-binding chaperones (calnexin and calreticulin), as well as stanniocalcin 2 and OASIS. The down-regulation or non-activation of the molecular chaperons, whose expressions are known to be protective by increasing protein folding, may spell doom for the adaptive response. Exposure to aluminum did not have any significant effects on the expression of Bax and Bcl2 in astrocytes. CONCLUSIONS: The results of this study demonstrate that aluminum may induce apoptosis in astrocytes via ER stress by impairing the protein-folding machinery.


Asunto(s)
Hidróxido de Aluminio/toxicidad , Apoptosis/efectos de los fármacos , Astrocitos/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Glicina/análogos & derivados , Chaperonas Moleculares/genética , Pliegue de Proteína/efectos de los fármacos , Hidróxido de Aluminio/metabolismo , Animales , Astrocitos/metabolismo , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Chaperón BiP del Retículo Endoplásmico , Endorribonucleasas/metabolismo , Glicina/metabolismo , Glicina/toxicidad , Ratones , Chaperonas Moleculares/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , ARN/efectos de los fármacos , ARN Mitocondrial , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Tunicamicina/metabolismo , Regulación hacia Arriba/efectos de los fármacos
11.
Int Immunopharmacol ; 97: 107637, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33895479

RESUMEN

Asthma is characterized by airway remodeling. Glucocorticoid induced transcript 1 (GLCCI1) was reported to be associated with the development of asthma, while its exact mechanism is still not clear. In our study, ovalbumin (OVA) combined with aluminum hydroxide were used to establish asthmatic mouse model. ELISA assay was fulfilled to ensure the concentration of inflammatory factors in both bronchoalveolar lavage fluid and serum. The pathological changes and collagen deposition in lung tissues were analyzed using H&E staining and Masson staining, respectively. The expression of proteins was measured using western blot, and the expression of GLCCI1 mRNA was ensured by qRT-PCR. Here, we demonstrated that OVA-induced inflammation, lung structural remodeling and collagen deposition in asthmatic mice was notably improved by hydroprednisone treatment or GLCCI1 overexpressing. The expression of GLCCI1 was decreased, while IL-13, periostin and TGF-ß1 were increased in the lung tissue of asthmatic mice. Importantly, upregulation of GLCCI1 suppressed the expression of IL-13, periostin and TGF-ß1, phosphorylation of Smad2 and Smad3, and extracellular matrix (ECM) deposition-related proteins expression. IL-13-induced upregulation of periostin and TGF-ß1 expression, phosphorylation of Smad2 and Smad3, and ECM deposition in airway epithelial cells (AECs) was repressed by GLCCI1 increasing. Furthermore, our results showed that overexpression of GLCCI1 repressed the effect of IL-13 on AECs via inhibiting periostin expression. Overall, our data revealed that GLCCI1 limited the airway remodeling in mice with asthma through inhibiting IL-13/periostin/TGF-ß1 signaling pathway. Our data provided a novel target for asthma treatment.


Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/inmunología , Asma/inmunología , Pulmón/patología , Receptores de Glucocorticoides/metabolismo , Hidróxido de Aluminio/administración & dosificación , Hidróxido de Aluminio/toxicidad , Animales , Asma/inducido químicamente , Asma/tratamiento farmacológico , Asma/patología , Moléculas de Adhesión Celular/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Interleucina-13/metabolismo , Pulmón/efectos de los fármacos , Pulmón/inmunología , Ratones , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunología , Prednisona/administración & dosificación , Receptores de Glucocorticoides/agonistas , Transducción de Señal/inmunología , Factor de Crecimiento Transformador beta1/metabolismo
12.
Neurotoxicology ; 83: 166-178, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33290785

RESUMEN

The European Union's REACH Regulation requires determination of potential health and environmental effects of chemicals in commerce. The present case study examines the application of REACH guidance for health hazard assessments of three high production volume (HPV) aluminium (Al) substances: metallic aluminium, aluminium oxide, and aluminium hydroxide. Among the potential adverse health consequences of aluminium exposure, neurotoxicity is one of the most sensitive targets of Al toxicity and the most critical endpoint. This case study illustrates integration of data from multiple lines of evidence into REACH weight of evidence evaluations. This case study then explains how those results support regulatory decisions on classification and labelling. Challenges in the REACH appraisal of Al compounds include speciation, solubility and bioavailability, application of assessment factors, read-across rationale and differences with existing regulatory standards. Lessons learned from the present case study relate to identification and evaluation of toxicologic and epidemiologic data; assessing data relevance and reliability; development of derived no-effect levels (DNELs); addressing data gaps and preparation of chemical safety reports.


Asunto(s)
Hidróxido de Aluminio/toxicidad , Óxido de Aluminio/toxicidad , Aluminio/toxicidad , Sistema Nervioso/efectos de los fármacos , Síndromes de Neurotoxicidad/etiología , Pruebas de Toxicidad , Aluminio/farmacocinética , Hidróxido de Aluminio/farmacocinética , Óxido de Aluminio/farmacocinética , Animales , Europa (Continente) , Unión Europea , Humanos , Sistema Nervioso/metabolismo , Sistema Nervioso/patología , Sistema Nervioso/fisiopatología , Síndromes de Neurotoxicidad/metabolismo , Síndromes de Neurotoxicidad/patología , Síndromes de Neurotoxicidad/fisiopatología , Medición de Riesgo , Toxicocinética
13.
ACS Appl Mater Interfaces ; 13(34): 40415-40428, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34470103

RESUMEN

Toxoplasma gondii (T. gondii) infection causes severe zoonotic toxoplasmosis, which threatens the safety of almost one-third of the human population globally. However, there is no effective protective vaccine against human toxoplasmosis. This necessitates anti-T. gondii vaccine development, which is a main priority of public health. In this study, we optimized the adjuvant system 04 (AS04), a vaccine adjuvant constituted by 3-O-desacyl-4'-monophosphoryl lipid A (a TLR4 agonist) and aluminum salts, by packing it within natural extracts of ß-glucan particles (GPs) from Saccharomyces cerevisiae to form a GP-AS04 hybrid adjuvant system. Through a simple mixing procedure, we loaded GP-AS04 particles with the total extract (TE) of T. gondii lysate, forming a novel anti-T. gondii vaccine GP-AS04-TE. Results indicated that the hybrid adjuvant can efficiently and stably load antigens, mediate antigen delivery, facilitate the dendritic uptake of antigens, boost dendritic cell maturation and stimulation, and increase the secretion of pro-inflammatory cytokines. In the mouse inoculation model, GP-AS04-TE significantly stimulated the function of dendritic cells, induced a very strong TE-specific humoral and cellular immune response, and finally showed a strong and effective protection against toxoplasma chronic and acute infections. This work proves the potential of GP-AS04 for exploitation as a vaccine against a range of pathogens.


Asunto(s)
Adyuvantes de Vacunas/uso terapéutico , Hidróxido de Aluminio/uso terapéutico , Lípido A/análogos & derivados , Nanocompuestos/uso terapéutico , Vacunas Antiprotozoos/uso terapéutico , Toxoplasma/inmunología , Toxoplasmosis/prevención & control , Adyuvantes de Vacunas/química , Adyuvantes de Vacunas/toxicidad , Hidróxido de Aluminio/química , Hidróxido de Aluminio/inmunología , Hidróxido de Aluminio/toxicidad , Animales , Células Dendríticas/efectos de los fármacos , Polisacáridos Fúngicos/química , Polisacáridos Fúngicos/uso terapéutico , Polisacáridos Fúngicos/toxicidad , Inmunidad Celular/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Lípido A/química , Lípido A/inmunología , Lípido A/uso terapéutico , Lípido A/toxicidad , Masculino , Ratones Endogámicos C57BL , Nanocompuestos/química , Nanocompuestos/toxicidad , Fagocitos/efectos de los fármacos , Vacunas Antiprotozoos/química , Vacunas Antiprotozoos/inmunología , Vacunas Antiprotozoos/toxicidad , Saccharomyces cerevisiae/química , Extractos de Tejidos/química , Extractos de Tejidos/inmunología , Extractos de Tejidos/uso terapéutico , Extractos de Tejidos/toxicidad , Toxoplasma/química , Toxoplasmosis/inmunología , beta-Glucanos/química , beta-Glucanos/uso terapéutico , beta-Glucanos/toxicidad
14.
Chemosphere ; 249: 126449, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32208217

RESUMEN

Influence of floc breakage and re-growth on the release of natural dissolved organic matter (DOM) and dissolved Al was explored. Results indicated that Al species including monomeric species (Ala), medium polymer species (Alb), and colloidal or solid species (Alc) in polyaluminum chlorides (PACls) played significant role. At lower doses ranged from 5 to 20 mg/L, floc breakage damaged Ala-NOM bonds for AlCl3, causing obvious release of DOM and dissolved Al. After re-growth, dissolved Al mainly connected with broken flocs, rather than released DOM. Thus, after re-growth, DOM release was still remarkable, but additional removal of dissolved Al was observed. At higher doses above 20 mg/L, more Ala transformed to Alb and Alc. Due to the enmeshment effect induced by Alc coagulation, fewer DOM and dissolved Al were released after breakage, and additional removal of DOM and dissolved Al were attained after re-growth. For PAClAl13 which mainly contained Alb, at optimal dose, floc breakage generated the most severe release of DOM and dissolved Al, while the result after re-growth was just reverse. This was ascribed to stronger charge neutralization ability of Alb. Furthermore, the influence of floc breakage and re-growth on DOM and dissolved Al for PAClC was similar to that for AlCl3. The reason was fully analyzed in this research. This study may give further indication regarding reaction mechanisms of floc breakage and re-growth for PACls.


Asunto(s)
Aluminio/toxicidad , Eliminación de Residuos Líquidos/métodos , Hidróxido de Aluminio/toxicidad , Cloruros , Floculación , Polímeros/química
15.
Toxicology ; 259(3): 140-8, 2009 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-19428954

RESUMEN

This paper compares the pulmonary toxicokinetics and toxicodynamics of three different types of poorly soluble dusts examined in repeated rat inhalation bioassays (6h/day, 5 days/week, 4 weeks). In these studies the fate of particles was studied during a 3-6-month postexposure period. This retrospective analysis included two types of aluminum oxyhydroxides (AlOOH, boehmite), high purity calcined, and agglomerated nanosized aluminas of very low solubility with primary isometric particles of 10 or 40nm, and synthetic iron oxide black (Fe(3)O(4) pigment grade). Three metrics of dose (actual mass concentration, surface area concentration, mass-based lung burden) were compared with pulmonary toxicity characterized by bronchoalveolar lavage. The results of this analysis provide strong evidence that pulmonary toxicity (inflammation) corresponds best with the mass-based cumulative lung exposure dose. The inhalation study with a MMAD of approximately 0.5microm yielded a higher pulmonary dose than MMADs in the range of 1-2microm, a range most commonly used in repeated exposure inhalation studies. Hence, a key premise for the dosimetric adjustment across species is that comparable lung tissue doses should cause comparable effects. From that perspective, the determination of mass-based pulmonary lung burdens appears to be amongst the most important and critical nominator of dose and dose-related pulmonary toxicity.


Asunto(s)
Hidróxido de Aluminio/toxicidad , Óxido de Aluminio/toxicidad , Óxido Ferrosoférrico/toxicidad , Enfermedades Pulmonares/inducido químicamente , Nanoestructuras/toxicidad , Administración por Inhalación , Hidróxido de Aluminio/administración & dosificación , Hidróxido de Aluminio/farmacocinética , Óxido de Aluminio/administración & dosificación , Óxido de Aluminio/farmacocinética , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Recuento de Células , Óxido Ferrosoférrico/administración & dosificación , Óxido Ferrosoférrico/farmacocinética , Pulmón/anatomía & histología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Enfermedades Pulmonares/metabolismo , Masculino , Tamaño de los Órganos/efectos de los fármacos , Tamaño de la Partícula , Ratas , Ratas Wistar , Estudios Retrospectivos , Organismos Libres de Patógenos Específicos
16.
Artículo en Inglés | MEDLINE | ID: mdl-19718687

RESUMEN

BACKGROUND: An increasing number of women are being vaccinated during child-bearing years, including vaccination with BioThrax (Anthrax Vaccine Adsorbed, or AVA). As only a limited number of studies exist in humans that have examined the effects of AVA on reproductive health, this study was conducted in order to evaluate the impact AVA vaccination may have on pregnant female rabbits and their offspring. METHODS: Two hundred female rabbits were vaccinated with saline, adjuvant, or AVA twice prior to mating and on one of two occasions during gestation, in order to have exposure to the antigen during organogenesis. Blood samples were collected from does and fetuses/kits to assess the development and in utero transfer of antibodies to Bacillus anthracis protective antigen (anti-PA IgG). Half of the does underwent Caesarean-sectioning on gestation day 29 and a gross necropsy was performed on both the does and their fetuses. The other half were allowed to naturally deliver and gross necropsy of the does and their kits was performed on lactation day 29. RESULTS: ELISA results showed that anti-PA IgG was generated by the does and passed to the fetuses/kits at detectable levels. CONCLUSIONS: AVA directly, or indirectly through the production of anti-PA IgG, did not appear to have an adverse effect on the pregnant females or their offspring, as measured by mating and fertility indices, natural delivery observations, clinical signs, gross lesions, in utero growth and survival, morphological development, or kit viability.


Asunto(s)
Vacunas contra el Carbunco/toxicidad , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/inmunología , Toxinas Bacterianas/inmunología , Embrión de Mamíferos/efectos de los fármacos , Reproducción/efectos de los fármacos , Vacunas Sintéticas/toxicidad , Adyuvantes Inmunológicos/toxicidad , Hidróxido de Aluminio/toxicidad , Animales , Vacunas contra el Carbunco/inmunología , Embrión de Mamíferos/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Desarrollo Fetal/efectos de los fármacos , Exposición Materna , Intercambio Materno-Fetal/inmunología , Embarazo , Conejos , Reproducción/inmunología , Vacunas Sintéticas/inmunología
17.
Ecotoxicol Environ Saf ; 72(7): 1933-41, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19428107

RESUMEN

Coagulant dosing of stormwater runoff with polyaluminum chlorides (PACs) is used in numerous waterbodies to improve water clarity, but the potential risks of PACs to aquatic organisms in Lake Tahoe, California are not fully understood. To assess these risks, the USEPA 3-species toxicity test and a non-standard fish test using Japanese medaka (Oryzias latipes) were used to determine the toxicity of PAC-treated and non-treated stormwater samples to aquatic species. Stormwater samples were collected from three sites representing runoff from different urbanized areas in May 2004; samples received coagulant dosing using three different coagulants (JC1720, PAX-XL9, Sumalchlor50) at levels optimized with jar testing. Raw stormwaters were toxic to algae and fathead minnows (mortality). Treatment with coagulants increased toxicity to zooplankton (reproduction) and had no consistent effects on the other toxicity metrics.


Asunto(s)
Hidróxido de Aluminio/toxicidad , Monitoreo del Ambiente/métodos , Agua Dulce/análisis , Contaminantes Químicos del Agua/toxicidad , Purificación del Agua/métodos , Animales , California , Cyprinidae/crecimiento & desarrollo , Eucariontes/efectos de los fármacos , Eucariontes/crecimiento & desarrollo , Oryzias/crecimiento & desarrollo , Lluvia , Zooplancton/efectos de los fármacos , Zooplancton/crecimiento & desarrollo
18.
Neuro Endocrinol Lett ; 30 Suppl 1: 192-8, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20027170

RESUMEN

OBJECTIVES: The aim of this study is to assess the toxicity of PAX-18 in different developmental stages of common carp (Cyprinus carpio). The preparation PAX-18, with its active ingredient polyaluminium chloride (9% of Al), is a coagulation agent that is used mainly to precipitate phosphates, to prevent surface water eutrophication and incidences of cyanobacteria. It is applied to the water environment and thus could present a potential risk to fish. DESIGN: The toxicity tests were performed on common carp according to OECD (203, 210) methodologies. The acute toxic effect was evaluated for juveniles and the early development stage effect was observed in embryo-larval toxicity tests. The results of the toxicity tests (the number of dead individuals at particular test concentrations) were subjected to a probit analysis using an EKO-TOX 5.2 programme to determine the LC50 values of PAX-18. RESULTS: Acute toxicity value expressed as 96hLC50 was 753.1 +/- 24.3 mg.l-1 (67.8 mg.l-1 Al). Effect on early development stage expressed as the no observed effect concentration was 10 mg.l-1 (0.9 mg.l-1 Al), the lowest observed effect concentration was 50 mg.l-1 (4.5 mg.l-1 Al). No significant effects of the preparation PAX-18 in concentrations of 50 mg.l-1 of PAX-18 and lower were found on hatching, length and weight parameters, morphology and histopathology. CONCLUSION: The lethal concentration of PAX-18 found in acute toxicity tests on common carp was 7-14 times higher than the concentration which is usually applied to water (5-10 mg.l-1 Al). Moreover, fish in eutrophicated water sources are exposed to PAX-18 concentrations corresponding with the lowest observed effect concentration only for a short time, therefore the effect on them can be considered as minimal.


Asunto(s)
Hidróxido de Aluminio/toxicidad , Antibacterianos/toxicidad , Carpas/crecimiento & desarrollo , Hidróxido de Aluminio/administración & dosificación , Animales , Carpas/embriología , Relación Dosis-Respuesta a Droga , Polímeros/administración & dosificación , Polímeros/toxicidad
19.
J Hazard Mater ; 365: 405-412, 2019 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-30448553

RESUMEN

The number of products containing nanomaterials is increasing this last ten years. Information and literature about the end-of-life of nanocomposites often remains partial and does not address the overall fate and transformations of nanoparticles that may affect biological responses. This paper underlines that the physico-chemical features of nanoparticles can be modified by the incineration process and the available toxicological data on pristine nanofillers might not be relevant to assess the modified nanoparticles included in soot. Combustion tests have been performed at lab-scale using a cone calorimeter modified to collect fumes (particulate matter and gas phase) and have been characterized using various techniques. Nanocomposites selected were poly(ethylene vinyl acetate) containing Al-based nanoparticles, i.e. boehmites or alumina. Evaluations of in vitro cytotoxicity responses on pristine nanofillers, soot and residual ash, show that safe boehmite nanoparticles, become toxic due to a chemical modification after incineration process.


Asunto(s)
Hidróxido de Aluminio , Óxido de Aluminio , Nanoestructuras , Polivinilos , Aluminio , Hidróxido de Aluminio/química , Hidróxido de Aluminio/toxicidad , Óxido de Aluminio/química , Óxido de Aluminio/toxicidad , Animales , Incineración , Ratones , Nanoestructuras/química , Nanoestructuras/toxicidad , Polivinilos/química , Polivinilos/toxicidad , Células RAW 264.7 , Hollín/análisis
20.
Anal Chim Acta ; 1047: 197-207, 2019 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-30567650

RESUMEN

This study introduces a new strategy for periodic stacking of positively charged NiAl layered double hydroxides (LDHs) nanosheets with negatively charged monolayers of graphene (G) by systematically optimizing several parameters in a controlled co-feeding fashion and resultant heterostacked NiAl LDH/G LBL nanocomposites have been practically applied in sensitive detection of dopamine released from live cells as early Parkinson's disease (PD) diagnostic tool. PD is the second most chronic neurodegenerative disorder with gradual progressive loss of movement and muscle control causing substantial disability and threatening the life seriously. Unfortunately majority of dopaminergic neurons present in substantia nigra of PD patients are destroyed before it is being clinically diagnosed, so early stages PD diagnosis is essential. Because of direct neighboring of extremely conductive graphene to semiconductive LDHs layers, enhanced intercalation capability of LDHs, and huge surface area with numerous active sites, good synergy effect is harvested in heteroassembled NiAl LDH/G LBL material, which in turn shows admirable electrocatalytic ability in DA detection. The interference induced by UA and AA is effectively eliminated especially after the modifying the electrode with Nafion. The outstanding electrochemical sensing performance of NiAl LDH/G LBL modified electrode has been achieved in terms of broad linear range and lowest real detection limit of 2 nM (S/N = 3) towards DA oxidation. Benefitting from superior efficiency, biosensor has been successfully used for real-time in-vitro tracking of DA efflux from live human nerve cell after being stimulated. We believe that our biosensing platform of structurally integrated well-ordered LBL heteroassembly by inserting graphene directly to the interlayer galleries of LDHs material will open up new avenue in diseases determination window.


Asunto(s)
Dopamina/análisis , Grafito/química , Nanocompuestos/química , Hidróxido de Aluminio/síntesis química , Hidróxido de Aluminio/química , Hidróxido de Aluminio/toxicidad , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Línea Celular Tumoral , Técnicas Electroquímicas/métodos , Electrodos , Grafito/síntesis química , Grafito/toxicidad , Humanos , Hidróxidos/síntesis química , Hidróxidos/química , Hidróxidos/toxicidad , Límite de Detección , Nanocompuestos/toxicidad , Níquel/química , Níquel/toxicidad , Electricidad Estática
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA