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1.
Nanomedicine (Lond) ; 17(18): 1281-1303, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-36254841

RESUMEN

Research on ZnO nanoparticles (NPs) has broad medical applications. However, the green synthesis of ZnO NPs involves a wide range of properties requiring optimization. ZnO NPs show toxicity at lower doses. This toxicity is a function of NP properties and pharmacokinetics. Moreover, NP toxicity and pharmacokinetics are affected by the species type and age of the animals tested. Physiologically based pharmacokinetic (PBPK) modeling offers a mechanistic platform to scrutinize the colligative effect of the interplay between these factors, which reduces the need for in vivo studies. This review provides a guide to choosing green synthesis conditions that result in minimal toxicity using a mechanistic tool, namely PBPK modeling.


Asunto(s)
Nanopartículas del Metal , Nanopartículas , Óxido de Zinc , Animales , Óxido de Zinc/toxicidad , Óxido de Zinc/farmacocinética , Toxicocinética , Nanopartículas/toxicidad , Nanopartículas del Metal/toxicidad
2.
Int J Mol Sci ; 22(21)2021 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-34769475

RESUMEN

Nano-sized zinc oxide (nano-ZnO) affects lipid deposition, but its absorption patterns and mechanisms affecting lipid metabolism are still unclear. This study was undertaken to investigate the molecular mechanism of nano-ZnO absorption and its effects on lipid metabolism in the intestinal tissues of a widely distributed freshwater teleost yellow catfish Pelteobagrus fulvidraco. We found that 100 mg/kg dietary nano-ZnO (H-Zn group) significantly increased intestinal Zn contents. The zip6 and zip10 mRNA expression levels were higher in the H-Zn group than those in the control (0 mg/kg nano-ZnO), and zip4 mRNA abundances were higher in the control than those in the L-Zn (50 mg/kg nano-ZnO) and H-Zn groups. Eps15, dynamin1, dynamin2, caveolin1, and caveolin2 mRNA expression levels tended to reduce with dietary nano-ZnO addition. Dietary nano-ZnO increased triglyceride (TG) content and the activities of the lipogenic enzymes glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and isocitrate dehydrogenase (ICDH), upregulated the mRNA abundances of lipogenic genes 6pgd, fatty acid synthase (fas), and sterol regulatory element binding protein 1 (srebp1), and reduced the mRNA expression of farnesoid X receptor (fxr) and small heterodimer partner (shp). The SHP protein level in the H-Zn group was lower than that in the control and the L-Zn group markedly. Our in vitro study indicated that the intestinal epithelial cells (IECs) absorbed nano-ZnO via endocytosis, and nano-Zn-induced TG deposition and lipogenesis were partially attributable to the endocytosis of nano-ZnO in IECs. Mechanistically, nano-ZnO-induced TG deposition was closely related to the metal responsive transcription factor 1 (MTF-1)-SHP pathway. Thus, for the first time, we found that the lipogenesis effects of nano-ZnO probably depended on the key gene shp, which is potentially regulated by MTF1 and/or FXR. This novel signaling pathway of MTF-1 through SHP may be relevant to explain the toxic effects and lipotoxicity ascribed to dietary nano-ZnO addition.


Asunto(s)
Endocitosis/fisiología , Mucosa Intestinal , Lípidos/toxicidad , Lipogénesis/efectos de los fármacos , Óxido de Zinc/farmacocinética , Alimentación Animal/toxicidad , Animales , Bagres , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Dieta , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Intestinos/efectos de los fármacos , Intestinos/metabolismo , Intestinos/patología , Lípidos/farmacocinética , Redes y Vías Metabólicas/genética , Nanopartículas del Metal/toxicidad , Regulación hacia Arriba/efectos de los fármacos , Zinc/metabolismo , Zinc/farmacocinética , Óxido de Zinc/química , Óxido de Zinc/toxicidad
3.
Molecules ; 26(3)2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33499293

RESUMEN

Applications of metal oxide nanoparticles in the agriculture sector are being extensively included as the materials are considered superior. In the present work, zinc oxide nanoparticle (ZnO NPs), with a developing fertilizer, is applied in the fortification of rice grain yield and nutrient uptake enhancement. To evaluate the role of ZnO NP, two field experiments were conducted during the 2018 and 2019 seasons. ZnO NPs were small, nearly spherical, and their sizes equal to 31.4 nm, as proved via the dynamic light scattering technique. ZnO NPs were applied as a fertilizer in different concentrations, varying between 20 and 60 mg/L as a foliar spray. The mixture of ZnSO4 and ZnO NP40 ameliorated yield component and nutrients (N, K, and Zn) uptake was enhanced compared to traditional ZnSO4 treatment. Nevertheless, the uptake of the phosphorous element (P) was adversely affected by the treatment of ZnO NPs. Thus, treatment via utilizing ZnO NPs as a foliar with a very small amount (40 ppm) with of basal ZnSO4 led to a good improvement in agronomic and physiological features; eventually, higher yield and nutrient-enriched rice grain were obtained.


Asunto(s)
Nanopartículas del Metal/química , Oryza/crecimiento & desarrollo , Óxido de Zinc/síntesis química , Transporte Biológico Activo , Grano Comestible/química , Grano Comestible/crecimiento & desarrollo , Grano Comestible/metabolismo , Fertilizantes , Alimentos Fortificados/análisis , Tecnología Química Verde/métodos , Humanos , Nanopartículas del Metal/administración & dosificación , Nanopartículas del Metal/ultraestructura , Microscopía Electrónica , Nanotecnología , Valor Nutritivo , Oryza/química , Oryza/metabolismo , Difracción de Rayos X , Óxido de Zinc/administración & dosificación , Óxido de Zinc/farmacocinética
4.
Mol Pharm ; 17(10): 3857-3869, 2020 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-32833457

RESUMEN

Disulfiram (DSF) is an FDA-approved anti-alcoholic drug that has recently proven to be effective in cancer treatment. However, the short half-life in the bloodstream and the metal ion-dependent antitumor activity significantly limited the further application of DSF in the clinical field. To this end, we constructed a silk fibroin modified disulfiram/zinc oxide nanocomposites (SF/DSF@ZnO) to solubilize and stabilize DSF, and, more importantly, achieve pH triggered Zn2+ release and subsequent synergistic antitumor activity. The prepared SF/DSF@ZnO nanocomposites were spherical and had a high drug loading. Triggered by the lysosomal pH, SF/DSF@ZnO could induce the rapid release of Zn2+ under the acidic conditions and caused nanoparticulate disassembly along with DSF release. In vitro experiments showed that cytotoxicity of DSF could be enhanced by the presence of Zn2+, and further amplified when encapsulated into SF/DSF@ZnO nanocomposites. It was confirmed that the significantly amplified cytotoxicity of SF/DSF@ZnO was resulted from pH-triggered Zn2+ release, inhibited cell migration, and increased ROS production. In vivo study showed that SF/DSF@ZnO nanocomposites significantly increased the tumor accumulation and prolonged the retention time. In vivo antitumor experiments in the xenograft model showed that SF/DSF@ZnO exerted the highest tumor-inhibition rate among all the drug treatments. Therefore, this exquisite study established silk fibroin-modified disulfiram/zinc oxide nanocomposites, SF/DSF@ZnO, where ZnO not only acted as a delivery carrier but also served as a metal ion reservoir to achieve synergistic antitumor efficacy. The established DSF nanoformulation displayed excellent therapeutic potential in future cancer treatment.


Asunto(s)
Antineoplásicos/farmacocinética , Nanocompuestos/administración & dosificación , Neoplasias/tratamiento farmacológico , Zinc/farmacocinética , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Bombyx/química , Cationes Bivalentes/farmacocinética , Línea Celular Tumoral/trasplante , Modelos Animales de Enfermedad , Disulfiram/administración & dosificación , Disulfiram/química , Disulfiram/farmacocinética , Composición de Medicamentos/métodos , Liberación de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Femenino , Fibroínas/química , Semivida , Humanos , Concentración de Iones de Hidrógeno , Ratones , Neoplasias/patología , Óxido de Zinc/administración & dosificación , Óxido de Zinc/química , Óxido de Zinc/farmacocinética
5.
Hum Exp Toxicol ; 39(10): 1318-1332, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32347117

RESUMEN

Various studies in rodents have shown that nanoparticles are transferred to the breast milk. Under the present study, lactating Wistar rats were repetitively gavaged 5, 25, and 50 mg/kg bw of zinc oxide nanoparticles (ZnO-NPs) and 50 mg kg-1 bw of bulk zinc oxide (bZnO) for 19 days after parturition. The results showed that ZnO-NPs were absorbed in the small intestine of dams and distributed to the liver. Furthermore, ZnO-NPs were distributed to the intestine and liver of rat pups through dam's milk. No significant change in body weight was observed in the dams treated with ZnO-NPs or bZnO and their offsprings as compared to the control group. The spleen weight significantly increased in the rat dams treated with 50 mg kg-1 of ZnO-NPs. ZnO-NPs were mostly excreted through feces. The levels of liver cytochrome P450 reductase and serum total antioxidant capacity significantly decreased in the rat dams treated with ZnO-NPs (50 mg kg-1) and their offsprings. The levels of serum cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and liver injury marker enzymes (alanine aminotransferase and aspartate aminotransferase) significantly increased in the rat dams treated with ZnO-NPs (25 and 50 mg kg-1) and their offsprings. The level of immunoglobulin A secretion in the intestinal fluid of rat dams and their offsprings is significantly increased by increasing the dose of ZnO-NPs. Histopathology of intestine and liver of offsprings whose rat dams were treated with ZnO-NPs (50 mg kg-1) showed gross pathological changes. These results provide information for the safety evaluation of ZnO-NPs use during lactation. In conclusion, a dose-dependent postnatal transfer of ZnO-NPs is hazardous to the breastfed offsprings.


Asunto(s)
Lactancia , Leche/metabolismo , Nanopartículas/toxicidad , Óxido de Zinc/farmacocinética , Óxido de Zinc/toxicidad , Administración Oral , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Heces/química , Femenino , Inmunoglobulina A/metabolismo , Interleucina-1beta/sangre , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , NADPH-Ferrihemoproteína Reductasa/metabolismo , Ratas Wistar , Medición de Riesgo , Factor de Necrosis Tumoral alfa/sangre
7.
J Biomed Opt ; 25(1): 1-19, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31939224

RESUMEN

We describe the contribution of our in vivo multiphoton microscopy (MPM) studies over the last ten years with DermaInspect;® (JenLab, Germany), a CE-certified medical tomograph based on detection of fluorescent biomolecules, to the assessment of possible penetration of nanoparticulate zinc oxide in sunscreen through human skin. At the time we started our work, there was a strong movement for the precautionary principle to be applied to the use of nanoparticles in consumer products due to a lack of knowledge. The combined application of different MPM modalities, including spectral imaging, fluorescence lifetime imaging, second harmonic fluorescence generation, and phosphorescence microscopy, has provided overwhelming evidence that nanoparticle zinc oxide particles do not penetrate human skin when applied to various skin types with a range of methods of topical sunscreen application. MPM has also been used to study the viable epidermal morphology and redox state in supporting the safe use of topical zinc oxide nanoparticles. The impact of this work is emphasized by the recent proposed rule by the United States FDA on Sunscreen Drug Products for Over-the-Counter Human Use, which listed only zinc oxide and titanium dioxide of the currently marketed products to be generally recognized as safe and effective.


Asunto(s)
Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Nanopartículas/metabolismo , Absorción Cutánea/fisiología , Piel/metabolismo , Protectores Solares/farmacocinética , Óxido de Zinc/farmacocinética , Humanos
8.
Mater Sci Eng C Mater Biol Appl ; 108: 110459, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31924031

RESUMEN

In this work, a new pH-responsive nanohybrid carrier was prepared with chelating ZnO-dopamine (Zn-d) on the surface of graphene oxide. Doxorubicin (DOX) as a model drug was loaded on the resulted nanohybrid. The characteristics of Zn-d-rGO nanohybrid (NH) determined using Fourier transformed infrared spectroscopy (FT-IR), X-ray Diffraction spectroscopy (XRD), UV-Visible spectroscopy, Scanning Electron Microscope (SEM), EDX and AFM. The BET analysis showed a specific surface area of 37.16 m2/g and the obtained nanohybrid indicated a high loading capacity of DOX up to 99.7%, and the release profile displayed a pH-dependent discharge in the acidic environment for14 days. The cytotoxicity of the prepared nanohybrid was measured against T47D and MCF10A cells and it confirmed that as-prepared nanohybrid has high toxicity against cancer cells and lower effect against human breast cell. Meanwhile, the prepared nanohybrids showed well antimicrobial activity against gram-positive and negative bacteria. The obtained results showed that the prepared nanohybrid (Zn-d-rGO) could potentially be used as a safe carrier for drug delivery systems.


Asunto(s)
Antibacterianos , Quelantes , Dopamina , Doxorrubicina , Portadores de Fármacos , Grafito , Nanopartículas/química , Óxido de Zinc , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Línea Celular Tumoral , Quelantes/química , Quelantes/farmacocinética , Quelantes/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Dopamina/química , Dopamina/farmacocinética , Dopamina/farmacología , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacología , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Grafito/química , Grafito/farmacocinética , Grafito/farmacología , Humanos , Concentración de Iones de Hidrógeno , Óxido de Zinc/química , Óxido de Zinc/farmacocinética , Óxido de Zinc/farmacología
9.
J Colloid Interface Sci ; 559: 51-64, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-31610305

RESUMEN

Aiming at the inefficiency and toxicity in traditional antitumor therapy, a novel multifunctional nanoplatform was constructed based on hollow mesoporous carbon (HMC) to achieve triple stimuli response and dual model antitumor therapy via chemo-photothermal synergistic effect. HMC was used as an ideal nanovehicle with a high drug loading efficiency as well as a near-infrared (NIR) photothermal conversion agent for photothermal therapy. Acid-dissoluble, luminescent ZnO quantum dots (QDs) were used as the proper sealing agents for the mesopores of HMC, conjugated to HMC via disulfide linkage to prevent drug (doxorubicin, abbreviated as Dox) premature release from Dox/HMC-SS-ZnO. After cellular endocytosis, the Dox was released in a pH, GSH and NIR laser triple stimuli-responsive manner to realize accurate drug delivery. Moreover, the local hyperthermia effect induced by NIR irradiation could promote the drug release, enhance cell sensitivity to chemotherapeutic agents, and also directly kill cancer cells. As expected, Dox/HMC-SS-ZnO exhibited a high drug loading capacity of 43%, well response to triple stimuli and excellent photothermal conversion efficiency η of 29.7%. The therapeutic efficacy in 4T1 cells and multicellular tumor spheroids (MCTSs) demonstrated that Dox/HMC-SS-ZnO + NIR had satisfactory chemo-photothermal synergistic effect with a combination index (CI) of 0.532. The cell apoptosis rate of the combined treatment group was more than 95%. The biodistribution and pharmacodynamics studies showed its biosecurity to normal tissues and synergistic inhibition effect to tumor cells. These distinguished results indicated that the Dox/HMC-SS-ZnO nanoplatform is potential to realize efficient triple stimuli-responsive drug delivery and dual model chemo-photothermal synergistic antitumor therapy.


Asunto(s)
Antineoplásicos/química , Carbono/química , Terapia Combinada/métodos , Portadores de Fármacos/química , Nanopartículas/química , Puntos Cuánticos/química , Óxido de Zinc/química , Animales , Antineoplásicos/farmacocinética , Apoptosis/efectos de los fármacos , Materiales Biocompatibles/química , Línea Celular Tumoral , Permeabilidad de la Membrana Celular , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Liberación de Fármacos , Colorantes Fluorescentes/química , Humanos , Rayos Infrarrojos , Ratones Endogámicos BALB C , Fototerapia/métodos , Porosidad , Propiedades de Superficie , Distribución Tisular , Óxido de Zinc/farmacocinética
10.
IET Nanobiotechnol ; 13(6): 640-649, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31432799

RESUMEN

New drug delivery system (ZnO@CMS) of the redox and pH dual-stimuli responsive based on colloidal mesoporous silica nanoparticles (CMS) has been designed, in which zinc oxide quantum dots (ZnO QDs) as a capping agent was conjugated on the surface of nanoparticles by amide bonds. The release behaviour of doxorubicin (DOX) as the model drug from ZnO@CMS (ZnO@CMS-DOX) indicated the redox and pH dual-stimuli responsive properties due to the acidic dissolution of ZnO QDs and cleavage of the disulphide bonds. The haemolysis and bovine serum albumin adsorption assays showed that the modification of ZnO QDs on the mesoporous silica nanoparticles modified by mercapto groups (CMS-SH)(ZnO@CMS) had better biocompatibility compared to CMS-SH. The cell viability and cellular uptake tests revealed that the ZnO@CMS might achieve the antitumour effect on cancer cells due to the cytotoxicity of ZnO QDs. Therefore, ZnO@CMS might be potential nanocarriers of the drug delivery system in cancer therapy. The in vivo evaluation of ZnO@CMS would be carried out in future work.


Asunto(s)
Antineoplásicos/administración & dosificación , Portadores de Fármacos , Nanopartículas/química , Puntos Cuánticos/química , Dióxido de Silicio/química , Óxido de Zinc/química , Adsorción , Animales , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/síntesis química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Sistemas de Liberación de Medicamentos , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7 , Nanopartículas/metabolismo , Neoplasias/tratamiento farmacológico , Oxidación-Reducción , Porosidad , Puntos Cuánticos/metabolismo , Conejos , Albúmina Sérica Bovina/metabolismo , Óxido de Zinc/metabolismo , Óxido de Zinc/farmacocinética
11.
Artículo en Inglés | MEDLINE | ID: mdl-30690156

RESUMEN

The release of engineered nanoparticles in the aquatic environment could pose a threat to the biota. The purpose of the study was to examine the influence of surface water characteristics on zinc oxide nanoparticles (nZnO) and ZnS04 toxicity to the freshwater mussel Dreissena polymorpha. Mussels were exposed to an equivalent concentration of 25 µg/L Zn as either nZnO or ZnSO4 for 96 h at 15 °C in 4 types of surface waters: green water (high conductivity and pH with low natural organic matter content), brown water (low conductivity and pH with high natural organic matter content), diluted municipal effluent (high conductivity and pH with high urban organic matter content) and aquarium water (treated green water with organic matter removed). After the exposure period, mussels were analyzed for air-time survival, total and labile Zn levels in tissues, lipid metabolism (phospholipase A2, triglycerides levels) and oxidative stress (glutathione S-transferase, arachidonate cyclooxygenase, lipid peroxidation). The data revealed that mussels exposed to ZnSO4 in controlled aquarium water accumulated more total and labile Zn tissues, decreased oxidative stress and triglycerides and increased air time survival. While nZnO had few effects in aquarium water, oxidative stress was enhanced and total Zn in tissues were decreased in brown water and diluted municipal effluent and triglycerides were higher in nZn-exposed mussels in brown water. Air-time survival was decreased in mussels kept in green water and nZnO. It was also decreased in mussels exposed to ZnSO4 in green water and diluted municipal effluent. In conclusion, the fate and toxic effects of Zn could be influenced by both the chemical form (nanoparticles or ionic Zn) and surface water properties in freshwater mussels.


Asunto(s)
Dreissena/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Óxido de Zinc/farmacocinética , Óxido de Zinc/toxicidad , Animales , Disponibilidad Biológica , Transporte Biológico , Biomarcadores , Contaminantes Químicos del Agua/farmacocinética , Contaminantes Químicos del Agua/toxicidad , Sulfato de Zinc/farmacocinética , Sulfato de Zinc/toxicidad
12.
Drug Chem Toxicol ; 42(1): 84-93, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30103634

RESUMEN

In recent years, nanoparticles are being used extensively in personal healthcare products such as cosmetics, sunscreens, soaps, and shampoos. Particularly, metal oxide nanoparticles are gaining competence as key industrial constituents, progressing toward a remarkable rise in their applications. Zinc oxide and titanium oxide nanoparticles are the most commonly employed metal oxide nanoparticles in sunscreens, ointments, foot care, and over the counter topical products. Dermal exposure to these metal oxides predominantly occurs through explicit use of cosmetic products and airway exposure to nanoparticle dusts is primarily mediated via occupational exposure. There is a compelling need to understand the toxicity effects of nanoparticles which can easily enter the cells and induce oxidative stress. Consequently, these products have become a direct source of pollution in the environment and thereby greatly impact our ecosystem. A complete understanding of the toxicity mechanism of nano-ZnO is intended to resolve whether and to what extent such nanoparticles may pose a threat to the environment and to human beings. In this review article, we have discussed the characteristics of metal oxide nanoparticles and its applications in the cosmetic industry. We have also highlighted about their toxicity effects and their impact on human health.


Asunto(s)
Cosméticos/química , Nanopartículas/toxicidad , Óxido de Zinc/toxicidad , Animales , Línea Celular , Cosméticos/normas , Relación Dosis-Respuesta a Droga , Humanos , Nanopartículas/química , Nanopartículas/metabolismo , Propiedades de Superficie , Pruebas de Toxicidad , Óxido de Zinc/química , Óxido de Zinc/farmacocinética
13.
Toxicol Mech Methods ; 29(4): 300-311, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30489211

RESUMEN

Zinc oxide (ZnO) is the most commonly used nanoparticles among different nanoparticles. Its applications ranged from personal care products, sensors, antibacterial creams, and biomedical applications. The broad range of applications raises concern in regards to their potential toxicity. Therefore, it is required to understand their toxicity mechanism and pattern on various levels. The primary aim of this review is to summarize the cytotoxicity, genotoxicity, neurotoxicity, and developmental toxicity of ZnO nanoparticles in various kinds of cells in vitro and in vivo. Literatures available on ZnO nanoparticles toxicity suggest that dissolution, organism dependent cellular uptake, generation of reactive oxygen species (ROS), and induced inflammatory responses seem to be common factors which govern the toxicity of ZnO nanoparticles.


Asunto(s)
Daño del ADN , Exposición a Riesgos Ambientales/efectos adversos , Nanopartículas/toxicidad , Síndromes de Neurotoxicidad/etiología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Óxido de Zinc/toxicidad , Animales , Supervivencia Celular/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Femenino , Humanos , Nanopartículas/metabolismo , Síndromes de Neurotoxicidad/metabolismo , Embarazo , Óxido de Zinc/farmacocinética
14.
J Invest Dermatol ; 139(2): 308-315, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30448212

RESUMEN

Zinc oxide is a widely used broad-spectrum sunscreen, but concerns have been raised about the safety of its nanoparticle (NP) form. We studied the safety of repeated application of agglomerated zinc oxide (ZnO) NPs applied to human volunteers over 5 days by assessing the skin penetration of intact ZnO-NPs and zinc ions and measuring local skin toxicity. Multiphoton tomography with fluorescence lifetime imaging microscopy was used to directly visualize ZnO-NP skin penetration and viable epidermal metabolic changes in human volunteers. The fate of ZnO-NPs was also characterized in excised human skin in vitro. ZnO-NPs accumulated on the skin surface and within the skin furrows but did not enter or cause cellular toxicity in the viable epidermis. Zinc ion concentrations in the viable epidermis of excised human skin were slightly elevated. In conclusion, repeated application of ZnO-NPs to the skin, as used in global sunscreen products, appears to be safe, with no evidence of ZnO-NP penetration into the viable epidermis nor toxicity in the underlying viable epidermis. It was associated with the release and penetration of zinc ions into the skin, but this did not appear to cause local toxicity.


Asunto(s)
Nanopartículas/administración & dosificación , Piel/metabolismo , Protectores Solares/toxicidad , Óxido de Zinc/toxicidad , Adulto , Femenino , Fluoresceínas/química , Voluntarios Sanos , Humanos , Microscopía Intravital , Microscopía de Fluorescencia por Excitación Multifotónica , Piel/diagnóstico por imagen , Piel/efectos de los fármacos , Absorción Cutánea , Protectores Solares/administración & dosificación , Protectores Solares/farmacocinética , Distribución Tisular , Tomografía , Pruebas de Toxicidad Subaguda , Adulto Joven , Óxido de Zinc/administración & dosificación , Óxido de Zinc/farmacocinética
15.
Environ Pollut ; 245: 510-518, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30458381

RESUMEN

There is still no consensus over the specific effects of metal-based nanoparticles when compared with the conventional metal salts. Here, the accumulation and toxicity of ZnO-NPs and ZnCl2 in Enchytraeus crypticus over time (1-14 d) were investigated using a sand-solution exposure medium and applying a toxicokinetics and toxicodynamics approach. For both Zn forms, body Zn concentration in the organisms was dependent on both the exposure concentration and exposure time, with equilibrium being reached after 7-14 days of exposure. Generally, the uptake and elimination rate constants (Ku and Ke1) were smaller for ZnO-NPs (5.74-12.6 mg kg-1d-1 and 0.17-0.39 d-1) than for ZnCl2 (8.32-40.1 mg kg-1d-1 and 0.31-2.05 d-1), suggesting that ionic Zn was more accessible for E. crypticus than nanoparticulate Zn. Based on external exposure concentrations, LC50s for ZnO-NPs and ZnCl2 decreased with time from 123 to 67 Zn mg L-1 and from 86 to 62 Zn mg L-1, reaching an almost similar ultimate value within 14 d. LC50s based on body Zn concentrations were almost constant over time (except for 1 d) for both ZnO-NPs and ZnCl2, with overall LC50body of Zn being 1720 and 1306 mg kg-1 dry body weight, respectively. Body Zn concentration, which considers all available pathways, was a good predictor of dynamic toxicity of ZnCl2, but not for ZnO-NPs. This may be attributed to the specific internal distribution and detoxification mechanisms of ZnO-NPs. The particles from ZnO-NPs dominated the accumulation (>75%) and toxicity (∼100%). Our results suggest that dynamic aspects should be taken into account when assessing and comparing NPs and metals uptake and consequent patterns of toxicity.


Asunto(s)
Cloruros/farmacocinética , Cloruros/toxicidad , Oligoquetos/metabolismo , Contaminantes del Suelo/farmacocinética , Contaminantes del Suelo/toxicidad , Compuestos de Zinc/farmacocinética , Compuestos de Zinc/toxicidad , Óxido de Zinc/farmacocinética , Óxido de Zinc/toxicidad , Animales , Dosificación Letal Mediana , Nanopartículas del Metal/toxicidad , Especies Centinela , Suelo/química , Contaminantes del Suelo/análisis , Toxicocinética , Zinc/metabolismo
16.
ACS Appl Mater Interfaces ; 11(1): 449-456, 2019 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-30525399

RESUMEN

Mesoporous zinc oxide (ZnO) scaffolds coated with drop-cast graphene oxide (GO) flakes are proposed to be a novel bilayer system featuring bioactivity, biocompatibility, and promising loading/release properties for controlled drug-delivery systems. The high-surface-area ZnO scaffolds show clear apatite deposition, but their particular surface chemistry and topography prevent the formation of a continuous coating, resulting in micrometric crystalline apatite aggregates after 28 days in simulated body fluid (SBF). When gentamicin sulfate (GS) is considered as a model molecule, pure ZnO scaffolds also show functional GS loading efficiency, with fast in vitro release kinetics driven by a simple diffusion mechanism. Strikingly, the bioactivity and GS delivery properties of mesoporous ZnO are efficiently triggered by drop-casting GO flakes atop the mesoporous scaffold surface. The resulting ZnO@GO bilayer scaffolds show the formation of a uniform apatite coating after 28 days in SBF and demonstrate a biocompatible behavior, supporting the culture of SaOS-2 osteoblast-like cells. Moreover, the GO coating also leads to a barrier-layer effect, preventing fast GS release, particularly in the short time range. This barrier effect, coupled with the existence of nanopores within the GO structure, sieves drug molecules from the mesoporous ZnO matrix and allows for a delayed release of the GS molecule. We, thus, demonstrated a new-generation ZnO@GO bilayer system as effective multifunctional and biocompatible scaffold for bone tissue engineering.


Asunto(s)
Materiales Biocompatibles Revestidos , Sistemas de Liberación de Medicamentos , Gentamicinas , Grafito , Osteoblastos/metabolismo , Óxido de Zinc , Huesos/citología , Huesos/metabolismo , Línea Celular Tumoral , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacocinética , Materiales Biocompatibles Revestidos/farmacología , Gentamicinas/química , Gentamicinas/farmacocinética , Gentamicinas/farmacología , Grafito/química , Grafito/farmacocinética , Grafito/farmacología , Humanos , Osteoblastos/citología , Porosidad , Ingeniería de Tejidos , Óxido de Zinc/química , Óxido de Zinc/farmacocinética , Óxido de Zinc/farmacología
17.
Part Fibre Toxicol ; 15(1): 39, 2018 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-30340606

RESUMEN

BACKGROUND: The extensive biological applications of zinc oxide nanoparticles (ZnO NPs) in stomatology have created serious concerns about their biotoxicity. In our previous study, ZnO NPs were confirmed to transfer to the central nervous system (CNS) via the taste nerve pathway and cause neurodegeneration after 30 days of tongue instillation. However, the potential adverse effects on the brain caused by tongue-instilled ZnO NPs are not fully known. METHODS: In this study, the biodistribution of Zn, cerebral histopathology and inflammatory responses were analysed after 30 days of ZnO NPs tongue instillation. Moreover, the molecular mechanisms underlying neuroinflammation in vivo were further elucidated by treating BV2 and PC12 cells with ZnO NPs in vitro. RESULTS: This analysis indicated that ZnO NPs can transfer into the CNS, activate glial cells and cause neuroinflammation after tongue instillation. Furthermore, exposure to ZnO NPs led to a reduction in cell viability and induction of inflammatory response and calcium influx in BV2 and PC12 cells. The mechanism underlying how ZnO NPs induce neuroinflammation via the Ca2+-dependent NF-κB, ERK and p38 activation pathways was verified at the cytological level. CONCLUSION: This study provided a new way how NPs, such as ZnO NPs, induce neuroinflammation via the taste nerve translocation pathway, a new mechanism for ZnO NPs-induced neuroinflammation and a new direction for nanomaterial toxicity analysis.


Asunto(s)
Encéfalo/efectos de los fármacos , Calcio/metabolismo , Nanopartículas/toxicidad , Síndromes de Neurotoxicidad/inmunología , Lengua/efectos de los fármacos , Óxido de Zinc/toxicidad , Animales , Encéfalo/inmunología , Encéfalo/metabolismo , Citocinas/genética , Expresión Génica/efectos de los fármacos , Inflamación , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , FN-kappa B/metabolismo , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/metabolismo , Células PC12 , Ratas , Ratas Wistar , Distribución Tisular , Lengua/inmunología , Lengua/metabolismo , Óxido de Zinc/farmacocinética
18.
Plant Physiol Biochem ; 130: 604-612, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30121512

RESUMEN

This work focused on the toxicity evaluation of ZnO NPs and their uptake and transportation in a significant crop plant, Rice (Oryza sativa L.). Under hydroponic condition, 25, 50 and 100 mg/L ZnO NPs could inhibit the growth of rice seedlings by reducing their biomass comparing with Zn2+ (13.82 mg/L) treatment and the control. In addition, physiological index was determined, involving the decrease of the chlorophyll content, which was further confirmed by the down-regulation of photosynthetic pigment related genes. Based on the expression levels of the genes encoding three antioxidant enzyme, e.g. Catalase (EC 1.11.1.6), Ascorbate peroxidase (EC 1.11.1.11) and Superoxide dismutase (EC 1.15.1.1), the oxidative damage was found in ZnO NPs exposed rice. On the other hand, by ultra-thin slicing and transmission electron microscopy, ZnO NPs were observed in the intercellular space and cytoplasm of rice root cells, and their transport to aerial tissue from roots were further confirmed by inductively coupled plasma atomic emission spectrometer. Overall, ZnO NPs could be uptaken by rice in the form of ions or particles, which further affected plant growth and development at phenotypic, physiological and molecular levels.


Asunto(s)
Nanopartículas/toxicidad , Oryza/efectos de los fármacos , Óxido de Zinc/toxicidad , Clorofila/metabolismo , Relación Dosis-Respuesta a Droga , Microscopía Electrónica de Transmisión , Nanopartículas/metabolismo , Oryza/metabolismo , Estrés Oxidativo/efectos de los fármacos , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Óxido de Zinc/farmacocinética
19.
IET Nanobiotechnol ; 12(6): 706-713, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30104442

RESUMEN

The increasing use of nanoparticles and their occurrence in the environment has made it imperative to elucidate their impact on the environment. Although several studies have advanced the authors' understanding of nanoparticle-plant interactions, their knowledge of the exposure of plants to nanoparticles and their effects on edible crop plants remain meager and is often paradoxical. The aim of this study was to increase their knowledge on the effect of zinc oxide (ZnO) nanoparticles on eggplant seed germination and seedling growth. ZnO nanoparticles had a negative effect on the growth of eggplant in plant tissue-culture conditions, as the growth of seedlings decreased with the increase in the concentration of ZnO nanoparticles. In contrast, ZnO nanoparticles enhanced eggplant growth under greenhouse conditions. The accumulation of ZnO nanoparticles in various parts of eggplant was observed through scanning electron microscopy of both plant tissue-culture and greenhouse-raised eggplant seedlings. To the best of their knowledge, this is the first study to report on ZnO nanoparticle accumulation in eggplant and its effect on seed germination and seedling growth.


Asunto(s)
Nanopartículas del Metal , Solanum melongena , Óxido de Zinc/farmacología , Óxido de Zinc/farmacocinética , Germinación/efectos de los fármacos , Hojas de la Planta/efectos de los fármacos , Raíces de Plantas/efectos de los fármacos , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Semillas/efectos de los fármacos , Solanum melongena/efectos de los fármacos , Solanum melongena/crecimiento & desarrollo , Solanum melongena/metabolismo , Distribución Tisular
20.
Int J Mol Sci ; 19(2)2018 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-29415484

RESUMEN

Zinc oxide (ZnO) nanoparticles (NPs) are widely used as a Zn supplement, because Zn plays a role in many cellular and immune functions but public concern about their potentially undesirable effects on the human body is growing. When NPs are added in food matrices, interactions between NPs and food components occur, which can affect biological systems. In this study, interactions between ZnO NPs and saccharides were investigated by measuring changes in hydrodynamic radius, zeta potential and solubility and by quantifying amounts of adsorbed saccharides on NPs; acacia honey, sugar mixtures (containing equivalent amounts of fructose, glucose, sucrose and maltose) and monosaccharide solutions were used as model compounds. Biological responses of NPs dispersed in different saccharides were also evaluated in human intestinal cells and rats in terms of cytotoxicity, cellular uptake, intestinal transport and oral absorption. The results demonstrate that the hydrodynamic radii and zeta potentials of NPs were highly affected by saccharides. In addition, trace nutrients influenced NP/saccharide interactions and interactive effects between saccharides on the interactions were found. NPs in all saccharides increased inhibition of cell proliferation and enhanced cellular uptake. Oral absorption of NPs was highly enhanced by 5% glucose, which is in-line with intestinal transport result. These findings show that ZnO NPs interact with saccharides and these interactions affects biological responses.


Asunto(s)
Nanopartículas del Metal/química , Monosacáridos/química , Óxido de Zinc/química , Animales , Transporte Biológico , Línea Celular , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Hidrodinámica , Mucosa Intestinal/metabolismo , Nanopartículas del Metal/ultraestructura , Monosacáridos/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Solubilidad , Óxido de Zinc/metabolismo , Óxido de Zinc/farmacocinética
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