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1.
Nanotechnology ; 33(20)2022 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-35090149

RESUMEN

In recent years, nanozymes based on two-dimensional (2D) nanomaterials have been receiving great interest for cancer photothermal therapy. 2D materials decorated with nanoparticles (NPs) on their surface are advantageous over conventional NPs and 2D material based systems because of their ability to synergistically improve the unique properties of both NPs and 2D materials. In this work, we report a nanozyme based on flower-like MoS2nanoflakes (NFs) by decorating their flower petals with NCeO2using polyethylenimine (PEI) as a linker molecule. A detailed investigation on toxicity, biocompatibility and degradation behavior of fabricated nanozymes in wild-typeDrosophila melanogastermodel revealed that there were no significant effects on the larval size, morphology, larval length, breadth and no time delay in changing larvae to the third instar stage at 7-10 d for MoS2NFs before and after NCeO2decoration. The muscle contraction and locomotion behavior of third instar larvae exhibited high distance coverage for NCeO2decorated MoS2NFs when compared to bare MoS2NFs and control groups. Notably, the MoS2and NCeO2-PEI-MoS2NFs treated groups at 100µg ml-1covered a distance of 38.2 mm (19.4% increase when compared with control) and 49.88 mm (no change when compared with control), respectively. High-resolution transmission electron microscopy investigations on the new born fly gut showed that the NCeO2decoration improved the degradation rate of MoS2NFs. Hence, nanozymes reported here have huge potential in various fields ranging from biosensing, cancer therapy and theranostics to tissue engineering and the treatment of Alzheimer's disease and retinal therapy.


Asunto(s)
Materiales Biocompatibles/toxicidad , Cerio/toxicidad , Disulfuros/toxicidad , Molibdeno/toxicidad , Nanoestructuras/toxicidad , Animales , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacocinética , Cerio/administración & dosificación , Cerio/química , Cerio/farmacocinética , Disulfuros/administración & dosificación , Disulfuros/química , Disulfuros/farmacocinética , Drosophila melanogaster , Tracto Gastrointestinal/metabolismo , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Larva/metabolismo , Locomoción/efectos de los fármacos , Ensayo de Materiales , Tasa de Depuración Metabólica , Molibdeno/administración & dosificación , Molibdeno/química , Molibdeno/farmacocinética , Contracción Muscular/efectos de los fármacos , Nanoestructuras/administración & dosificación , Nanoestructuras/química , Polietileneimina/administración & dosificación , Polietileneimina/química , Polietileneimina/farmacocinética , Polietileneimina/toxicidad , Especies Reactivas de Oxígeno/metabolismo
2.
Plant Cell Physiol ; 62(5): 913-921, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-33826734

RESUMEN

Molybdenum (Mo) is an essential element for plant growth and is utilized by several key enzymes in biological redox processes. Rice assimilates molybdate ions via OsMOT1;1, a transporter with a high affinity for molybdate. However, other systems involved in the molecular transport of molybdate in rice remain unclear. Here, we characterized OsMOT1;2, which shares amino acid sequence similarity with AtMOT1;2 and functions in vacuolar molybdate export. We isolated a rice mutant harboring a complete deletion of OsMOT1;2. This mutant exhibited a significantly lower grain Mo concentration than the wild type (WT), but its growth was not inhibited. The Mo concentration in grains was restored by the introduction of WT OsMOT1;2. The OsMOT1;2-GFP protein was localized to the vacuolar membrane when transiently expressed in rice protoplasts. At the reproductive growth stage of the WT plant, OsMOT1;2 was highly expressed in the 2nd and lower leaf blades and nodes. The deletion of OsMOT1;2 impaired interorgan Mo allocation in aerial parts: relative to the WT, the mutant exhibited decreased Mo levels in the 1st and 2nd leaf blades and grains but increased Mo levels in the 2nd and lower leaf sheaths, nodes and internodes. When the seedlings were exposed to a solution with a high KNO3 concentration in the absence of Mo, the mutant exhibited significantly lower nitrate reductase activity in the shoots than the WT. Our results suggest that OsMOT1;2 plays an essential role in interorgan Mo distribution and molybdoenzyme activity in rice.


Asunto(s)
Proteínas Portadoras/metabolismo , Molibdeno/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Transporte Biológico , Proteínas Portadoras/genética , Regulación de la Expresión Génica de las Plantas , Molibdeno/farmacocinética , Mutación , Nitrato-Reductasa/genética , Nitrato-Reductasa/metabolismo , Nitratos/metabolismo , Oryza/genética , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente , Semillas/genética , Semillas/metabolismo , Distribución Tisular
3.
Biochem Biophys Res Commun ; 516(4): 1090-1096, 2019 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-31279525

RESUMEN

"Bottom-up" method is a popular approach for the preparation of molybdenum disulfide quantum dots (MoS2 QDs) benefitting from less time consumption and no high-powered sonication required. But the relatively low fluorescent quantum yield of the obtained MoS2 QDs and the rare study about their in vivo behavior stimulate us to do more research in this area. In this paper, we proposed a "bottom-up" hydrothermal method to prepare MoS2 QDs with a quantum yield (QY) of 34.55% by optimizing a series of reaction conditions. The successful fluorescence imaging of tumor cells in vitro and in vivo as well as the systematic in vivo behavior study such as biocompatibility, biodistribution and metabolism route provided the good basis for their wider biomedical applications.


Asunto(s)
Neoplasias del Colon/diagnóstico por imagen , Disulfuros/análisis , Molibdeno/análisis , Imagen Óptica/métodos , Puntos Cuánticos/análisis , Animales , Línea Celular Tumoral , Disulfuros/farmacocinética , Humanos , Ratones Endogámicos BALB C , Molibdeno/farmacocinética , Nanotecnología/métodos , Puntos Cuánticos/ultraestructura , Distribución Tisular
4.
Xenobiotica ; 49(3): 332-338, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29460662

RESUMEN

1. WTX101 (bis-choline tetrathiomolybdate) is an investigational copper (Cu)-protein-binding agent developed for the treatment of Wilson disease (WD), a rare genetic disorder caused by mutations in the ATP7B Cu-transporter and resulting in toxic Cu accumulation. 2. Mass balance of a single intravenous WTX101 dose, measured as molybdenum (Mo), was assessed over 168 h in control (Long Evans Agouti [LEA]) and Long-Evans Cinnamon (LEC) rats, a WD model. 3. In LEC rats, Mo was partially excreted (up to 45%); 29% by renal clearance, and faecal clearance, still ongoing at 168 h, accounted for 16%. In contrast, in LEA rats, Mo was almost fully excreted (∼87%); 79% was renally cleared with only 7% faecal excretion. 4. In LEC rats, the proportion of faecal to renal Mo excretion was enhanced (4:6) compared to controls (1:9). 5. Substantially more Mo was found in LEC liver and kidney compared with LEA tissues, in line with tissue Cu distribution. 6. These findings are consistent with the WTX101 mechanism of action: in the WD model, excess Cu is removed from hepatic metallothionein and retained within the stable tetrathiomolybdate-Cu-albumin tripartite complex, preventing tetrathiomolybdate degradation and resulting in less urinary elimination and greater faecal excretion than in controls.


Asunto(s)
Quelantes/farmacocinética , Cobre/metabolismo , Degeneración Hepatolenticular/tratamiento farmacológico , Molibdeno/farmacocinética , Animales , Bilis/química , Transporte Biológico/genética , Quelantes/metabolismo , Quelantes/uso terapéutico , Heces/química , Molibdeno/metabolismo , Molibdeno/uso terapéutico , Ratas , Orina/química
5.
Artículo en Inglés | MEDLINE | ID: mdl-29869939

RESUMEN

Spent hydroprocessing catalysts are known to contain a variety of potentially toxic metals and therefore studies on the bioavailability and mobility of these metals are critical for understanding the possible environmental risks of the spent catalysts. This study evaluates the different chemical fractions/forms of aluminium (Al), nickel (Ni), and molybdenum (Mo) in spent hydroprocessing catalyst and the changes they undergo during bioleaching with Acidithiobacillus ferrooxidans. In the spent catalyst (prior to bioleaching), Al was primarily present in its residual form, suggesting its low environmental mobility. However, Ni comprised mainly an exchangeable fraction, indicating its high environmental mobility. Molybdenum was mainly in the oxidizable form (47.1%), which indicated that highly oxidizing conditions were required to liberate it from the spent catalyst. During bioleaching the exchangeable, reducible and oxidizable fractions of all the metals were leached, whereas the residual fractions remained largely unaffected. At the end of bioleaching process, the metals remaining in the bioleached sample were predominantly in the residual fraction (98.3-99.5%). The 'risk assessment code' (RAC) and IR analysis also demonstrated that the environmental risks of the bioleached residue were significantly lower compared to the untreated spent catalyst. The results of this study suggest that bioleaching is an effective method in removing the metals from spent catalysts and the bioleached residue poses little environmental risk.


Asunto(s)
Acidithiobacillus/metabolismo , Aluminio/aislamiento & purificación , Fraccionamiento Químico/métodos , Molibdeno/aislamiento & purificación , Níquel/aislamiento & purificación , Aluminio/química , Aluminio/farmacocinética , Biodegradación Ambiental , Catálisis , Hidrólisis , Metales/química , Metales/aislamiento & purificación , Metales/farmacocinética , Molibdeno/química , Molibdeno/farmacocinética , Níquel/química , Níquel/farmacocinética , Industria del Petróleo y Gas , Oxidación-Reducción , Aguas Residuales/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Contaminantes Químicos del Agua/farmacocinética
6.
Salud Publica Mex ; 59(5): 548-555, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29267652

RESUMEN

OBJECTIVE: This study determined the main dietary sources of urinary molybdenum (Mo) concentrations in a sample of 124 pregnant women in Mexico. MATERIALS AND METHODS: Dietary data was collected during pregnancy, through a semi-qualitative food frequency questionnaire, with information of 84 foods. Urine Mo levels were determined by atomic absorption spectrometry, for at least two trimesters of pregnancy. The associations with Mo levels were estimated by generalized mixed effect regression models. RESULTS: Between 5.8 to 12.7% of the samples were above the 95th percentile of urinary Mo distribution reported by National Health and Nutrition Examination Survey (NHANES) 2009-2010 for women (151 µg/L and 148 µg/g creatinine). After bootstrap resampling was conducted, women with high-consumption of hot peppers (ß=1.34µg/g; 95% CI: 1.00-1.80; p= 0.05) had marginally higher urinary Mo concentration levels, creatinine adjusted, compared to women with low-consumption. CONCLUSION.: Hot chili pepper consumption may contribute to body burden Mo levels in this population.


Asunto(s)
Dieta , Molibdeno/orina , Adulto , Capsicum/química , Conducta Alimentaria , Femenino , Humanos , México , Molibdeno/farmacocinética , Molibdeno/toxicidad , Proyectos Piloto , Embarazo , Trimestres del Embarazo/orina , Efectos Tardíos de la Exposición Prenatal , Factores Socioeconómicos , Espectrofotometría Atómica , Adulto Joven
7.
Regul Toxicol Pharmacol ; 77: 223-9, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26972837

RESUMEN

Molybdenum is an essential trace element for mammalian, plant, and other animal systems. The Institute of Medicine (IOM) has established an Estimated Average Requirement (EAR) to assure sufficient molybdenum intakes for human populations; however excessive exposures can cause toxicity. As a result, several agencies have established exposure guidance values to protect against molybdenum toxicity, including a Reference Dose (RfD), Tolerable Daily Intake (TDI) and a Tolerable Upper Intake Level (UL). Biomonitoring for molybdenum in blood or urine in the general population is being conducted by the Canadian Health Measures Survey (CHMS) and the U.S. National Health and Nutrition Examination Survey (NHANES). Using pharmacokinetic data from controlled human dosing studies, Biomonitoring Equivalents (BEs) were calculated for molybdenum in plasma, whole blood, and urine associated with exposure guidance values set to protect against both nutritional deficits and toxicity. The BEEAR values in plasma, whole blood and urine are 0.5, 0.45 and 22 µg/L, respectively. The BEs associated with toxicity range from 0.9 to 31 µg/L in plasma, 0.8-28 µg/L in whole blood and 200-7500 µg/L in urine. These values can be used to interpret molybdenum biomonitoring data from a nutritional and toxicity perspective.


Asunto(s)
Monitoreo del Ambiente/métodos , Contaminantes Ambientales/sangre , Contaminantes Ambientales/orina , Molibdeno/sangre , Molibdeno/orina , Oligoelementos/sangre , Oligoelementos/orina , Factores de Edad , Animales , Biomarcadores/sangre , Biomarcadores/orina , Canadá , Relación Dosis-Respuesta a Droga , Contaminantes Ambientales/efectos adversos , Contaminantes Ambientales/farmacocinética , Femenino , Humanos , Masculino , Modelos Biológicos , Molibdeno/efectos adversos , Molibdeno/farmacocinética , Nivel sin Efectos Adversos Observados , Estado Nutricional , Ingesta Diaria Recomendada , Medición de Riesgo , Especificidad de la Especie , Oligoelementos/efectos adversos , Oligoelementos/farmacocinética
8.
Angew Chem Int Ed Engl ; 55(6): 2122-6, 2016 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-26710169

RESUMEN

Molybdenum oxide (MoOx) nanosheets with high near-infrared (NIR) absorbance and pH-dependent oxidative degradation properties were synthesized, functionalized with polyethylene glycol (PEG), and then used as a degradable photothermal agent and drug carrier. The nanosheets, which are relatively stable under acidic pH, could be degraded at physiological pH. Therefore, MoOx-PEG distributed in organs upon intravenous injection would be rapidly degraded and excreted without apparent in vivo toxicity. MoOx-PEG shows efficient accumulation in tumors, the acidic pH of which then leads to longer tumor retention of those nanosheets. Along with the capability of acting as a photothermal agent for effective tumor ablation, MoOx-PEG can load therapeutic molecules with high efficiencies. This concept of inorganic theranostic nanoagent should be relatively stable in tumors to allow imaging and treatment, while being readily degradable in normal organs to enable rapid excretion and avoid long-term retention/toxicity.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Molibdeno/farmacocinética , Nanoestructuras/administración & dosificación , Nanoestructuras/análisis , Óxidos/farmacocinética , Nanomedicina Teranóstica/métodos , Animales , Neoplasias de la Mama/patología , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/síntesis química , Portadores de Fármacos/química , Femenino , Concentración de Iones de Hidrógeno , Ratones , Ratones Endogámicos BALB C , Molibdeno/administración & dosificación , Molibdeno/química , Óxidos/administración & dosificación , Óxidos/química , Fototerapia , Polietilenglicoles/administración & dosificación , Polietilenglicoles/farmacocinética
9.
Anal Bioanal Chem ; 406(1): 239-47, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24162822

RESUMEN

To study the permeability of the blood-brain barrier (BBB) to arsenates, arsenite, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), molybdate, and methylmercury, and the transfer behavior of these species, we constructed an automatic online analytical system comprising a microdialysis sampling device, a minicolumn packed with nonfunctionalized poly(vinyl chloride) beads, and an inductively coupled plasma mass spectrometer for continuous in-vivo measurement of their dynamic variation in the extracellular space of the brains of living rats. By using ion-polymer interactions as a novel working mechanism for sample pretreatment of volume-limited microdialysate, we simplified the operating procedure of conventional solid-phase extraction and reduced the contribution to the blank of the chemicals used. After optimizing this hyphenated system, we measured its performance by analysis of NIST standard reference materials 1640a (trace elements in natural water) and 2672a (trace elements in human urine) and by in-vivo monitoring of the dynamic variation of the compounds tested in the extracellular fluid (ECF) of rat brain. We found that intraperitoneal administration led to observable BBB permeability of arsenates, arsenite, DMA, MMA, and molybdate. Nevertheless, the limited sensitivity of the system and the size of microdialysis samples meant that detection of MeHg in ECF remained problematic, even when we administered a dose of 20 mg MeHg kg(-1) body weight. On the basis of these practical demonstrations, we suggest that our analytical system could be used not only for dynamic monitoring of the transfer kinetics of the four arsenicals and molybdate in the rat brain but also to describe associated neurotoxicity in terms of exposure to toxic metals and their species.


Asunto(s)
Arsenicales/metabolismo , Barrera Hematoencefálica/metabolismo , Ácido Cacodílico/metabolismo , Permeabilidad Capilar , Compuestos de Metilmercurio/metabolismo , Molibdeno/metabolismo , Animales , Arsenicales/farmacocinética , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Ácido Cacodílico/farmacocinética , Electrodos Implantados , Inyecciones Intraperitoneales , Masculino , Compuestos de Metilmercurio/farmacocinética , Microdiálisis , Molibdeno/farmacocinética , Ratas , Ratas Sprague-Dawley , Espectrofotometría Atómica , Técnicas Estereotáxicas
10.
Regul Toxicol Pharmacol ; 70(3): 579-88, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24041747

RESUMEN

This study investigated the subchronic toxicity of molybdenum (Mo) in Sprague-Dawley rats given sodium molybdate dihydrate in the diet for 90days at dose levels of 0, 5, 17 or 60mgMo/kgbw/day. The study complied with OECD Test Guideline (TG) 408, with additional examination of estrus cycles and sperm count, motility, and morphology from OECD TG 416. The overall no-observed-adverse-effect level was 17mgMo/kgbw/day, based on effects on body weight, body weight gain, food conversion efficiency and renal histopathology (females only) at 60mgMo/kgbw/day. No treatment-related adverse effects on reproductive organ weights or histopathology, estrus cycles or sperm parameters were observed at any dose level. No adverse effects were observed in the high dose animals after the 60-day recovery period, with the exception that male rats did not fully recover from reduced body weight. Serum blood, liver and kidney samples were analyzed for molybdenum, copper, zinc, manganese, iron, cobalt and selenium; high levels of molybdenum and copper were found in the serum, blood, liver and kidneys of rats treated with 60mgMo/kgbw/day. In conclusion, the LOAEL and NOAEL for molybdenum were determined to be 60 and 17mgMo/kgbw/day, respectively.


Asunto(s)
Molibdeno/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Cobre/sangre , Cobre/metabolismo , Ciclo Estral/efectos de los fármacos , Femenino , Genitales/anatomía & histología , Genitales/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Hígado/anatomía & histología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Molibdeno/sangre , Molibdeno/farmacocinética , Nivel sin Efectos Adversos Observados , Ratas Sprague-Dawley , Recuento de Espermatozoides , Pruebas de Toxicidad Subcrónica
11.
Toxicology ; 467: 153098, 2022 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-35026344

RESUMEN

Molybdenum, lithium, and tungsten are constituents of many products, and exposure to these elements potentially occurs at work. Therefore it is important to determine at what levels they are toxic, and thus we set out to review their pulmonary toxicity, genotoxicity, and carcinogenicity. After pulmonary exposure, molybdenum and tungsten are increased in multiple tissues; data on the distribution of lithium are limited. Excretion of all three elements is both via faeces and urine. Molybdenum trioxide exerted pulmonary toxicity in a 2-year inhalation study in rats and mice with a lowest-observed-adverse-effect concentration (LOAEC) of 6.6 mg Mo/m3. Lithium chloride had a LOAEC of 1.9 mg Li/m3 after subacute inhalation in rabbits. Tungsten oxide nanoparticles resulted in a no-observed-adverse-effect concentration (NOAEC) of 5 mg/m3 after inhalation in hamsters. In another study, tungsten blue oxide had a LOAEC of 63 mg W/m3 in rats. Concerning genotoxicity, for molybdenum, the in vivo genotoxicity after inhalation remains unknown; however, there was some evidence of carcinogenicity of molybdenum trioxide. The data on the genotoxicity of lithium are equivocal, and one carcinogenicity study was negative. Tungsten seems to have a genotoxic potential, but the data on carcinogenicity are equivocal. In conclusion, for all three elements, dose descriptors for inhalation toxicity were identified, and the potential for genotoxicity and carcinogenicity was assessed.


Asunto(s)
Transformación Celular Neoplásica/inducido químicamente , Cloruro de Litio/toxicidad , Pulmón/efectos de los fármacos , Molibdeno/toxicidad , Neoplasias/inducido químicamente , Óxidos/toxicidad , Tungsteno/toxicidad , Animales , Carga Corporal (Radioterapia) , Pruebas de Carcinogenicidad , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Relación Dosis-Respuesta a Droga , Humanos , Exposición por Inhalación , Cloruro de Litio/farmacocinética , Pulmón/metabolismo , Pulmón/patología , Nanopartículas del Metal , Molibdeno/farmacocinética , Pruebas de Mutagenicidad , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Óxidos/farmacocinética , Medición de Riesgo , Tungsteno/farmacocinética
12.
Nutr Res Rev ; 24(2): 176-82, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22296933

RESUMEN

The rumen is the site of significant interactions between Cu, S and Mo. It also shows reactions between Cu, S and Fe. The interaction between Mo and S results in the formation of thiomolybdates, which in the absence of adequate quantities of rumen Cu are absorbed into the animal and bind to Cu in biological compounds. This is the cause of thiomolybdate toxicity, often misleadingly called Cu deficiency. The effects of thiomolybdates being absorbed into the animal are considered, especially how thiomolybdates bind to Cu-containing compounds such as enzymes, decreasing their activity without removing the active Cu component. The sources of Cu, Mo, Fe and S are examined, including the impacts of water and soil on the animal's intake. Within the present review we have been able to provide evidence that: all classes of thiomolybdates are formed in the rumen; in the absence of available Cu all thiomolybdates can be absorbed into the animal rapidly though the rumen wall or via the small intestine; thiomolybdates bind to Cu in biological compounds and are able to cause problems; effects of thiomolybdate are reversible in vivo and in vitro on cessation of thiomolybdate challenge; the tetra-thiomolybdate form is the most potent Cu binder with decreased potency with decreasing S in the compound. Fe will exacerbate a thiomolybdate problem but will not directly cause it.


Asunto(s)
Cobre/metabolismo , Molibdeno/farmacocinética , Rumen/metabolismo , Absorción/fisiología , Animales , Cobre/administración & dosificación , Absorción Intestinal/fisiología , Hierro/administración & dosificación , Molibdeno/administración & dosificación , Molibdeno/metabolismo , Molibdeno/toxicidad , Rumiantes , Suelo , Azufre/administración & dosificación , Azufre/metabolismo , Agua
13.
Ecotoxicol Environ Saf ; 74(1): 1-9, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20951431

RESUMEN

Mo toxicity to earthworms (Eisenia andrei), Collembola (Folsomia candida) and enchytraeids (Enchytraeus crypticus) was determined in 10 European soils and a standard artificial soil, freshly spiked with Na(2)MoO(4), after 28 days exposure. Mo affected survival only in three low pH sandy soils; in all other soils LC50 was >3200 mg Mo/kg dry soil. EC50 values for the reproduction toxicity of Mo were 129-2378 mg/kg for earthworms, 72->3396 mg/kg for Collembola, and 301->2820 mg/kg for enchytraeids. Variation in toxicity among soils could not be explained by differences in available (pore water, water and 0.01 M CaCl(2) extractable) Mo concentrations. Clay content best predicted the EC50 for Mo toxicity to earthworms, while toxicity of Mo for enchytraeids was best described by soil pH. For Collembola no relationships could be derived due to the absence of toxicity in most soils. Soil properties had a strong but species-specific effect on Mo toxicity to soil invertebrates.


Asunto(s)
Invertebrados/efectos de los fármacos , Molibdeno/toxicidad , Contaminantes del Suelo/toxicidad , Suelo/química , Animales , Artrópodos/efectos de los fármacos , Artrópodos/fisiología , Disponibilidad Biológica , Concentración de Iones de Hidrógeno , Invertebrados/clasificación , Invertebrados/fisiología , Molibdeno/farmacocinética , Oligoquetos/efectos de los fármacos , Oligoquetos/fisiología , Reproducción/efectos de los fármacos , Contaminantes del Suelo/química , Contaminantes del Suelo/farmacocinética , Solventes/química , Especificidad de la Especie , Factores de Tiempo , Pruebas de Toxicidad Crónica
14.
Arch Orthop Trauma Surg ; 131(9): 1299-308, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21298277

RESUMEN

INTRODUCTION: A patient with a total hip replacement developed optic, acoustic and peripheral neuropathy from metal ions intoxication, due to the wear products released from the prosthesis. Subsequently the kinetics of the metal ions was studied. MATERIALS AND METHODS: Massive wear and acute intoxication allowed a study of the metal ions kinetics and of EDTA treatment. RESULTS: Plasma and other organic fluids were saturated by each of the metal ions released from the exposed surface according to the solubility of each ion; a larger fraction of Co ions was bound within red cells, while the plasmatic fraction appeared more movable. In a patient with a prosthesis subjected to wear, the ions released are from the prosthetic and from the debris surface (spread in the body). The latter is a function of the number and size of particles. DISCUSSION: Revision of the prosthesis from the point of view of the metal ions kinetics corresponded to a reduction of the releasing surface because of debris washed out by irrigation and tissue excision; however, the metal particles spread by lymphatic circulation continued to release ions even though the source of wear had been removed. Early diagnosis of high metal wear can be ascertained with mass spectrometry and after revision high levels of metal ions can only be reduced with repeated chelating treatment. It is preferable not to revise fractured ceramic components with a polyethylene-metal articulation.


Asunto(s)
Cromo/efectos adversos , Cobalto/efectos adversos , Pérdida Auditiva Central/inducido químicamente , Prótesis de Cadera/efectos adversos , Molibdeno/efectos adversos , Enfermedades del Nervio Óptico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Quelantes/uso terapéutico , Cromo/farmacocinética , Cobalto/farmacocinética , Ácido Edético/uso terapéutico , Femenino , Pérdida Auditiva Central/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Molibdeno/farmacocinética , Enfermedades del Nervio Óptico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Diseño de Prótesis , Reoperación
15.
Nat Nanotechnol ; 16(6): 708-716, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33603238

RESUMEN

Many nanoscale biomaterials fail to reach the clinical trial stage due to a poor understanding of the fundamental principles of their in vivo behaviour. Here we describe the transport, transformation and bioavailability of MoS2 nanomaterials through a combination of in vivo experiments and molecular dynamics simulations. We show that after intravenous injection molybdenum is significantly enriched in liver sinusoid and splenic red pulp. This biodistribution is mediated by protein coronas that spontaneously form in the blood, principally with apolipoprotein E. The biotransformation of MoS2 leads to incorporation of molybdenum into molybdenum enzymes, which increases their specific activities in the liver, affecting its metabolism. Our findings reveal that nanomaterials undergo a protein corona-bridged transport-transformation-bioavailability chain in vivo, and suggest that nanomaterials consisting of essential trace elements may be converted into active biological molecules that organisms can exploit. Our results also indicate that the long-term biotransformation of nanomaterials may have an impact on liver metabolism.


Asunto(s)
Disulfuros/farmacocinética , Molibdeno/química , Molibdeno/farmacocinética , Nanoestructuras/química , Administración Intravenosa , Animales , Apolipoproteínas E/genética , Disponibilidad Biológica , Biotransformación , Proteínas Sanguíneas/metabolismo , Disulfuros/análisis , Femenino , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones Endogámicos BALB C , Ratones Transgénicos , Simulación de Dinámica Molecular , Molibdeno/análisis , Molibdeno/sangre , Nanoestructuras/administración & dosificación , Corona de Proteínas/química , Corona de Proteínas/metabolismo , Albúmina Sérica Humana/química , Albúmina Sérica Humana/metabolismo , Bazo/citología , Bazo/efectos de los fármacos , Distribución Tisular
16.
Clin Cancer Res ; 14(22): 7526-34, 2008 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-19010871

RESUMEN

PURPOSE: Copper chelation reduces the secretion of many angiogenic factors and reduces tumor growth and microvascular density in animal models. ATN-224 is a second-generation analogue of ammonium tetrathiomolybdate. The aim of our phase I study was to reduce serum copper levels, as measured by ceruloplasmin, to 5 to 15 mg/dL (normal 16-60) in 14 to 21 days, to determine the pharmacokinetic profile of ATN-224 and to evaluate dose-limiting toxicities. PATIENTS AND METHODS: Cohorts of patients were treated with escalating oral doses of ATN-224 until copper depletion followed by a titrated maintenance dose. RESULTS: Eighteen patients received 78 cycles of ATN-224. Mean baseline ceruloplasmin was 39.6 mg/dL. The maximum administered dose was 330 mg/d where grade 3 fatigue was dose-limiting. At the maximum tolerated dose of 300 mg/d, the median time to achieve target ceruloplasmin was 21 days, and toxicities included grade 3 anemia, grade 3 neutropenia, fatigue, and sulfur eructation. ATN-224 treatment caused a significant reduction (> 90%) in RBC superoxide dismutase 1 activity and circulating endothelial cells. Pharmacokinetic data indicate greater absorption of ATN-224 and more rapid ceruloplasmin reduction when administered with a proton pump inhibitor. Stable disease of > 6 months was observed in 2 patients. CONCLUSIONS: Oral ATN-224 is a well-tolerated therapy and at a loading dose of 300 mg/d leads to a reduction of serum ceruloplasmin levels in 80% patients within 21 days. A loading dose of 300 mg/d for 2 weeks followed by a titrated maintenance dose will be the recommended starting dose for phase II study.


Asunto(s)
Quelantes/efectos adversos , Quelantes/farmacocinética , Quelantes/uso terapéutico , Terapia por Quelación , Colina/efectos adversos , Colina/farmacocinética , Colina/uso terapéutico , Cobre/sangre , Molibdeno/efectos adversos , Molibdeno/farmacocinética , Molibdeno/uso terapéutico , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Ceruloplasmina/efectos de los fármacos , Citocinas/sangre , Citocinas/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Superóxido Dismutasa/sangre , Superóxido Dismutasa/efectos de los fármacos
17.
Sci Total Environ ; 657: 686-695, 2019 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-30677934

RESUMEN

This study assessed the impact of pre-definite redox potential (EH) on the release dynamics and distribution of As, Co, and Mo between the dissolved and colloidal phases as well as their potential mobility and phytoavailability in the sediment phase of a mining soil treated with rice hull biochar (BC). The experiment was conducted from controlled moderately-reducing to oxidizing conditions using an automated biogeochemical microcosm system. Arsenic and Mo were more abundant in the dissolved phase due to their predominant in potential mobile fractions, while Co was more abundant in the colloidal phase due to its association with Fe-(hydr)oxides. Biochar increased the dissolved and colloidal concentrations of As, the dissolved concentration of Co, and the colloidal concentration of Mo under oxidizing condition. On the other hand, the application of BC decreased the dissolved concentration of Mo and the colloidal concentration of Co in the first redox cycle under reducing-acidic condition, due to lower pH values, and chemistry of sulfide-sulfate and Fe/Mn oxides. The phytoavailability of As and Co were higher than their potential mobility in the sediment phase, while the same trend was not discerned for Mo. The potential mobility and phytoavailability of As and Co were high under oxic-acidic conditions. The potential mobility and phytoavailability of Mo might be increased under oxic condition due to the dissolution of Fe and Mn oxides under lower pH conditions, especially in the BC treated soil. Application of such rice hull BC to soil might stimulate the release of As, Co, and Mo under flooding conditions, which might increase the environmental and health risks in such wetland ecosystems.


Asunto(s)
Arsénico/análisis , Carbón Orgánico/química , Cobalto/análisis , Molibdeno/análisis , Contaminantes del Suelo/análisis , Arsénico/farmacocinética , Disponibilidad Biológica , China , Cobalto/farmacocinética , Coloides/química , Restauración y Remediación Ambiental , Concentración de Iones de Hidrógeno , Minería , Molibdeno/farmacocinética , Oxidación-Reducción , Contaminantes del Suelo/farmacocinética
18.
Nanoscale ; 11(11): 4767-4780, 2019 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-30816394

RESUMEN

Nano-MoS2 has been extensively investigated in materials science and biomedicine. However, the effects of different methods of exposure on their translocation, biosafety, and biotransformation-related degradability remain unclear. In this study, we combined the advantages of synchrotron radiation (SR) X-ray absorption near-edge structure (XANES) and high-resolution single-cell SR transmission X-ray microscopy (SR-TXM) with traditional analytical techniques to investigate translocation, precise degraded species/ratio, and correlation between the degradation and toxicity levels of polyvinylpyrrolidone-modified 2H-phase MoS2 nanosheets (MoS2-PVP NSs). These NSs demonstrated different biodegradability levels in biomicroenvironments with H2O2, catalase, and human myeloperoxidase (hMPO) (H2O2 < catalase < hMPO). The effects of NSs and their biodegraded byproducts on cell viability and 3D translocation at the single-cell level were also assessed. Toxicity and translocation in mice via intravenous (i.v.), intraperitoneal (i.p.), and intragastric (i.g.) administration routes guided by fluorescence (FL) imaging were investigated within the tested dosage. After i.g. administration, NSs accumulated in the gastrointestinal organs and were excreted from feces within 48 h. After i.v. injection, NSs showed noticeable clearance due to their decreased accumulation in the liver and spleen within 30 days when compared with that in the i.p. group, which exhibited slight accumulation in the spleen. This work paves the way for understanding the biological behaviors of nano-MoS2 using SR techniques that provide more opportunities for future applications.


Asunto(s)
Disulfuros/farmacocinética , Disulfuros/toxicidad , Molibdeno/farmacocinética , Molibdeno/toxicidad , Nanoestructuras/toxicidad , Povidona/farmacocinética , Povidona/toxicidad , Animales , Biotransformación , Supervivencia Celular/efectos de los fármacos , Disulfuros/administración & dosificación , Disulfuros/química , Vías de Administración de Medicamentos , Masculino , Ratones Endogámicos BALB C , Molibdeno/administración & dosificación , Molibdeno/química , Nanomedicina , Nanoestructuras/administración & dosificación , Nanoestructuras/química , Povidona/administración & dosificación , Povidona/química , Distribución Tisular
19.
Reprod Toxicol ; 84: 75-92, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30503857

RESUMEN

In an OECD Test Guideline 416 multigenerational study, groups of 24 male and 24 female Sprague-Dawley rats were administered sodium molybdate dihydrate at 0, 5, 17, or 40 mg molybdenum (Mo)/kg bw/day in the drinking water or 40 mg Mo/kg bw/day in the diet over two generations to assess reproductive toxicity. No adverse effect on reproductive function was observed at any dose level in either generation as indicated by no significant dose-related effect on estrus cycles, sperm parameters, mating, fertility, gestation, litter size, pup survival, growth or postnatal development. Systemic toxicity, including decreased body weight, food consumption (males only) and water consumption, was observed among both sexes given 40 mg Mo/kg bw/day in the diet. Serum levels of Mo and copper were increased in a dose-related manner. The No Observed Adverse Effect Levels (NOAEL) are 17 mg Mo/kg bw/day for systemic toxicity and 40 mg Mo/kg bw/day for reproductive toxicity.


Asunto(s)
Molibdeno/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Dieta , Agua Potable , Ingestión de Alimentos/efectos de los fármacos , Femenino , Masculino , Molibdeno/sangre , Molibdeno/farmacocinética , Molibdeno/orina , Nivel sin Efectos Adversos Observados , Embarazo , Ratas Sprague-Dawley , Fenómenos Fisiológicos Reproductivos/efectos de los fármacos
20.
ACS Appl Mater Interfaces ; 11(44): 41009-41018, 2019 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-31599564

RESUMEN

Inflammatory macrophage (Mφ)-mediated atherosclerosis is a leading cause of mortality and morbidity worldwide. Photothermal therapy (PTT) has been demonstrated as an efficient strategy in killing target cells, and its application in the treatment of inflammation in atherosclerosis is developing. However, the choice of nanomaterials, mechanisms, and side effects are seldom considered. In this study, semiconductor nanomaterials, that is, MoO2 nanoclusters, were synthesized and used for the first time in PTT for inflammatory Mφ-mediated atherosclerosis. Based on cell differential phagocytosis, the optimum amount of MoO2 and treatment time were selected to exert the maximum ablation effect on Mφ and minimal damage on endothelial cells without requiring additional target or selective groups. Moreover, MoO2-based PTT shows an excellent therapeutic effect on atherosclerosis by eliminating Mφ in animal models, with no significant side effects observed. This study explores a new method of nanotechnology and pharmaceutical development by using and optimizing cost-effective metal oxide nanostructures in the treatment of atherosclerosis and motivates further research on minimizing the side effects of related materials.


Asunto(s)
Aterosclerosis/terapia , Rayos Infrarrojos , Macrófagos/efectos de la radiación , Fagocitosis/efectos de la radiación , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Aterosclerosis/inmunología , Aterosclerosis/patología , Células de la Médula Ósea/citología , Arterias Carótidas/efectos de los fármacos , Arterias Carótidas/patología , Arterias Carótidas/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Modelos Animales de Enfermedad , Células Endoteliales/citología , Células Endoteliales/metabolismo , Humanos , Macrófagos/citología , Macrófagos/inmunología , Masculino , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Nanopartículas del Metal/toxicidad , Ratones , Ratones Noqueados , Molibdeno/química , Molibdeno/farmacocinética , Óxidos/química , Óxidos/farmacocinética , Fototerapia , Semiconductores , Distribución Tisular
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