RESUMEN
Abstract Cisplatin (CP) is used to treat various tumors. A main restriction of cisplatin is nephrotoxicity. This study aimed to evaluate the protective effects of ZnONPs on cisplatin-induced oxidative stress and rat kidney tissue damage. Eighty adult male Wistar rats (250g-270g) were divided into ten groups: Control (CON), Sham (SH), Bulk ZnO (BZnO), Chemical ZnONPs (ChZnONPs), Green ZnONPs (GrZnONPs), Cisplatin (CP), Cisplatin+BulkZnO (CP+BZnO), Cisplatin+Green ZnONPs (CP+GrZnONPs), Cisplatin+Chemical ZnONPs (CP+ChZnONPs), Cisplatin+Explant (CP+EX). CP was i.p administered 5mg/kg/week and BZnO, ChZnONPs and GrZnONPs were i.p administered at a dose of 5mg/kg/day. After 30 days of the treatment, the expression of apoptosis/anti apoptosis related genes oxidant/antioxidant factors and histological changes in the were studied. The CP-treated group showed a decrease in body weight, while the Co-administration of ZGNPs to CP-treated rats showed a significant increase compared to the CP group. The results showed that the increased mRNA level of bax, MDA and the decreased mRNA level of bcl2, SOD and CAT activities in kidney of CP group were improved when animals were treated with ZnO NPs. Our results showed that GrZnONPs, ChZnONPs and BZnO had the potential to protect against oxidative stress and cisplatin-induced neurotoxicity that this protective effect was more evident in GrZnONPs.
Asunto(s)
Animales , Masculino , Ratas , Óxido de Zinc/efectos adversos , Estrés Oxidativo , Nanopartículas/clasificación , Riñón/anomalías , HistologíaAsunto(s)
Dermatitis del Pañal , Errores Innatos del Metabolismo de los Metales , Óxido de Zinc , Dermatitis del Pañal/diagnóstico , Dermatitis del Pañal/tratamiento farmacológico , Dermatitis del Pañal/etiología , Humanos , Lactante , Índice de Severidad de la Enfermedad , Óxido de Zinc/efectos adversosRESUMEN
Adverse reactions to sunscreens are uncommon in relation to their widespread use [Loden et al. Br J Dermatol. 2011;165(2):255-62; Jansen et al. J Am Acad Dermatol. 2013;69(6):867 e861-814; quiz 881-862] and can be related to both active and inactive ingredients in sunscreen products [DiNardo et al. J Cosmet Dermatol. 2018;17(1):15-19; Barrientos et al. Contact Dermatitis. 2019;81(2):151-52]. Pathogenetically, the main cutaneous adverse reaction patterns to sunscreens can be divided into allergic and irritant contact dermatitis, phototoxic and photoallergic contact dermatitis, contact urticaria, and, in solitary cases, anaphylactic reactions [Lautenschlager et al. Lancet. 2007;370(9586):528-37]. A summary is provided in Table
Asunto(s)
Dermatitis Alérgica por Contacto/etiología , Dermatitis Irritante/etiología , Neoplasias Cutáneas/prevención & control , Protectores Solares/efectos adversos , Rayos Ultravioleta/efectos adversos , Dermatitis Alérgica por Contacto/patología , Dermatitis Alérgica por Contacto/prevención & control , Dermatitis Irritante/patología , Dermatitis Irritante/prevención & control , Unión Europea , Humanos , Vehículos Farmacéuticos/efectos adversos , Vehículos Farmacéuticos/química , Piel/efectos de los fármacos , Piel/patología , Piel/efectos de la radiación , Neoplasias Cutáneas/etiología , Protectores Solares/administración & dosificación , Protectores Solares/química , Titanio/administración & dosificación , Titanio/efectos adversos , Óxido de Zinc/administración & dosificación , Óxido de Zinc/efectos adversosRESUMEN
Preparations containing pigments have been used since ancient times to protect against negative effects of solar radiation. Since the 1950s, sunscreen products containing micronized TiO2 and ZnO have been marketed. These products were soon regarded as cosmetically unattrac-tive due to their property of remaining as a white paste on the skin, a result of particle sizes. In order to eliminate these unfavourable properties, particle size distribution was lowered into a range below 100 nm, a size threshold for decreasing the particle's optical property to reflect visible light. After 2000, new nanoparticulate organic filters were developed. Effects of both the inorganic and organic nanoparticulate substances - alone or in combination - with non-particulate UV filters were well documented and had shown great effectiveness. At the time, nanotechnology fuelled great hope in the progress of science and technology, including the health sector and cosmetics industry. Instead, influenced by images from the science fiction literature of self-replicating nanorobots destroying all living matter or health and environmental disasters caused by asbestos, fear of this new unknown amongst the general population has hindered acceptance and progress of nano-enabled products. Consumers have started to suspect that the particles permeate through skin, are absorbed by the blood and are distributed throughout the body, causing disease. Not least because of public pressure, cosmetics - which include sunscreen products - became the first product segment in which appropriately manufactured substances were subject to stringent rules. Despite advanced regulation and rigorous approval procedures for nanoparticulate UV filters, widespread reservations remain. Possible reasons could be a lack of knowledge of current legislation and unclear ideas about nature and behaviour of nanoparticles. Against this background, we discuss the nature and behaviour of nanoparticulate UV filters within finished products, on the skin and potentially in the skin, and the regulatory framework that ensures that nanoparticulate UV filters and the sunscreen products containing them are safe to use.
Asunto(s)
Seguridad de Productos para el Consumidor/normas , Nanopartículas/química , Protectores Solares/química , Rayos Ultravioleta/efectos adversos , Humanos , Nanopartículas/efectos adversos , Tamaño de la Partícula , Piel/efectos de los fármacos , Piel/metabolismo , Piel/efectos de la radiación , Absorción Cutánea , Protectores Solares/efectos adversos , Protectores Solares/farmacocinética , Protectores Solares/normas , Titanio/efectos adversos , Titanio/química , Óxido de Zinc/efectos adversos , Óxido de Zinc/químicaRESUMEN
Nanoscience paves the way for producing highly potent fertilizers and pesticides to meet farmer's expectations. This study investigated the physiological and molecular responses of soybean seedlings to the long-time application of zinc oxide nanoparticles (ZnO NPs) and their bulk type (BZnO) at 5 mg L-1 under the two application methods (I- foliar application; II- soil method). The ZnO NPs/BZnO treatments in a substance type- and method-dependent manner improved plant growth performance and yield. ZnO NPs transactionally upregulated the EREB gene. However, the expression of the bHLH gene displayed a contrary downward trend in response to the supplements. ZnO NPs moderately stimulated the transcription of R2R3MYB. The HSF-34 gene was also exhibited a similar upward trend in response to the nano-supplements. Moreover, the ZnONP treatments mediated significant upregulation in the WRKY1 transcription factor. Furthermore, the MAPK1 gene displayed a similar upregulation trend in response to the supplements. The foliar application of ZnONP slightly upregulated transcription of the HDA3 gene, while this gene showed a contrary slight downregulation trend in response to the supplementation of nutrient solution. The upregulation in the CAT gene also resulted from the nano-supplements. The concentrations of photosynthetic pigments exhibited an increasing trend in the ZnONP-treated seedlings. The applied treatments contributed to the upregulation in the activity of nitrate reductase and the increase in the proline concentrations. ZnO NPs induced the activity of antioxidant enzymes, including peroxidase and catalase by averages of 48.3% and 41%, respectively. The utilization of ZnO NPs mediated stimulation in the activity of phenylalanine ammonia-lyase and increase in soluble phenols. The findings further underline this view that the long-time application of ZnO NPs at low concentrations is a safe low-risk approach to meet agricultural requirements.
Asunto(s)
Antioxidantes/metabolismo , Carbono/metabolismo , Glycine max/efectos de los fármacos , Glycine max/metabolismo , Histona Desacetilasas/metabolismo , Nanopartículas/química , Nitrógeno/metabolismo , Metabolismo Secundario/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/metabolismo , Óxido de Zinc/farmacología , Biomarcadores/metabolismo , Fertilizantes , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Genes de Plantas , Histona Desacetilasas/genética , Fotosíntesis/efectos de los fármacos , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Plantones/efectos de los fármacos , Plantones/genética , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Transducción de Señal/genética , Glycine max/genética , Glycine max/crecimiento & desarrollo , Factores de Transcripción/genética , Regulación hacia Arriba/efectos de los fármacos , Óxido de Zinc/efectos adversosRESUMEN
Nano-based particles synthesized via green routes have a particular structure that is useful in biomedical applications as they provide cheap, eco-friendly, and non-toxic nanoparticles. In the present study, we reported the effect of various concentrations of Zinc oxide nanoparticles synthesized using A. lebbeck stem bark extract (ZnO NPsAL) as stabilizing agent on rat biochemical profiles and tissue morphology. Adult Wistar rats weighing 170 ± 5 g were randomly classified into eight groups of five rats each; Group A served as a control fed with normal diet and water. Groups B1, B2, C1, C2, D1, D2, and E were treated with 40 mg/kg and 80 mg/kg of the 0.01, 0.05, and 0.1 M biosynthesized ZnO NPsAL and zinc nitrate daily by the gavage method, respectively. The rats were anesthetized 24 h after the last treatment, blood samples, kidney, heart, and liver tissues were collected for biochemical and histopathological analysis. The rats mean body weight, serum alkaline phosphatase, alanine aminotransferase, creatinine, urea, bilirubin, protein, albumin, globulin, total cholesterol, triacylglycerol, and high-density lipoprotein were significantly altered with an increased concentration of biosynthesized ZnO NPsAL when compared with the control group (p < 0.05; n ≥ 5). Furthermore, histopathological analysis of treated rats' kidney, heart, and liver tissue revealed vascular congestion, tubular necrosis, inflammation, and cytoplasmic vacuolation. Biosynthesized ZnO NPsAL showed significant alteration in biochemical parameters and tissue morphology in rats with increasing concentrations of the nanoparticles.
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Albizzia/química , Nanopartículas , Corteza de la Planta/química , Extractos Vegetales/química , Óxido de Zinc , Animales , Masculino , Nanopartículas/administración & dosificación , Nanopartículas/química , Nanopartículas/uso terapéutico , Especificidad de Órganos , Ratas , Ratas Wistar , Óxido de Zinc/efectos adversos , Óxido de Zinc/química , Óxido de Zinc/farmacologíaRESUMEN
The use of inorganic nanoparticles (NPs) has expanded into various industries including food manufacturing, agriculture, cosmetics, and construction. This has allowed NPs access to the human gastrointestinal tract, yet little is known about how they may impact human health. As the gut microbiome continues to be increasingly implicated in various diseases of unknown etiology, researchers have begun studying the potentially toxic effects of these NPs on the gut microbiome. Unfortunately, conflicting results have limited researcher's ability to evaluate the true impact of NPs on the gut microbiome in relation to health. This review focuses on the impact of five inorganic NPs (silver, iron oxide, zinc oxide, titanium dioxide, and silicon dioxide) on the gut microbiome and gastrointestinal tract with consideration for various methodological differences within the literature. This is important as NP-induced changes to the gut could lead to various gut-related diseases. These include irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), celiac disease, and colorectal cancer. Research in this area is necessary as the use of NPs in various industries continues to grow along with the number of people suffering from chronic gastrointestinal diseases.
Asunto(s)
Compuestos Férricos/efectos adversos , Industria de Alimentos , Microbioma Gastrointestinal/efectos de los fármacos , Nanopartículas del Metal/efectos adversos , Nanopartículas del Metal/química , Dióxido de Silicio/efectos adversos , Plata/efectos adversos , Titanio/efectos adversos , Óxido de Zinc/efectos adversos , Enfermedad Celíaca/inducido químicamente , Enfermedad Celíaca/microbiología , Neoplasias Colorrectales/inducido químicamente , Neoplasias Colorrectales/microbiología , Disbiosis/inducido químicamente , Humanos , Enfermedades Inflamatorias del Intestino/inducido químicamente , Enfermedades Inflamatorias del Intestino/microbiología , Síndrome del Colon Irritable/inducido químicamente , Síndrome del Colon Irritable/microbiologíaRESUMEN
Inhalation of ZnO particles can cause inflammation of the airways and metal fume fever. It is unclear if different sizes of the particles alter these effects. However, various studies report higher biological activity of other nano-sized particles compared to microparticles. No effects at all were observed after inhalation of micro- and nano-sized zinc oxide (ZnO) particle concentrations of 0.5 mg/m3. Studies with different particle sizes of ZnO at higher exposures are not available. Accordingly, we hypothesized that inhalation of nano-sized ZnO particles induces stronger health effects than the inhalation of the same airborne mass concentration of micro-sized ZnO particles. 16 healthy volunteers (eight men, eight women) were exposed to filtered air and ZnO particles (2.0 mg/m3) for 2 h (one session with nano- and one with micro-sized ZnO) including 1 h of cycling at moderate workload. Effect parameters were symptoms, body temperature, inflammatory markers in blood and in induced sputum. Induced sputum was obtained at baseline examination, 22 h after exposure and at the end of the final test. The effects were assessed before, immediately after, about 22 h after, as well as two and three days after each exposure. Neutrophils, monocytes and acute-phase proteins in blood increased 22 h after micro- and nano-sized ZnO exposure. Effects were generally stronger with micro-sized ZnO particles. Parameters in induced sputum showed partial increases on the next day, but the effect strengths were not clearly attributable to particle sizes. The hypothesis that nano-sized ZnO particles induce stronger health effects than micro-sized ZnO particles was not supported by our data. The stronger systemic inflammatory responses after inhalation of micro-sized ZnO particles can be explained by the higher deposition efficiency of micro-sized ZnO particles in the respiratory tract and a substance-specific mode of action, most likely caused by the formation of zinc ions.
Asunto(s)
Mediadores de Inflamación/sangre , Nanopartículas del Metal/administración & dosificación , Sistema Respiratorio/efectos de los fármacos , Óxido de Zinc/administración & dosificación , Proteínas de Fase Aguda/metabolismo , Administración por Inhalación , Adulto , Ciclismo , Biomarcadores/sangre , Regulación de la Temperatura Corporal/efectos de los fármacos , Método Doble Ciego , Femenino , Humanos , Masculino , Nanopartículas del Metal/efectos adversos , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Nebulizadores y Vaporizadores , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Tamaño de la Partícula , Distribución Aleatoria , Sistema Respiratorio/metabolismo , Esputo/metabolismo , Factores de Tiempo , Adulto Joven , Óxido de Zinc/efectos adversos , Óxido de Zinc/metabolismoRESUMEN
In recent years, zinc oxide nanoparticles (ZnONPs) emerged as an excellent candidate in the field of optical, electrical, food packaging and particularly in biomedical research. ZnONPs show cancer cell specific toxicity via the pH-dependent (low pH) dissolution into Zn2+ ions, which generate reactive oxygen species and induce cytotoxicity in cancer cells. Further, ZnONPs have also been used as an effective carrier for the targeted delivery of several anticancer drugs into tumor cells. The increasing focus on ZnONPs resulted in the development of various synthesis approaches including chemical, pHysical, and green or biological for the manufacturing of ZnONPs. In this article, at first we have discussed the various synthesis methods of ZnONPs and secondly its biomedical applications. We have extensively reviewed the anticancer mechanism of ZnONPs on different types of cancers considering its size, shape and surface charge dependent cytotoxicity. Photoirradiation with UV light or NIR laser further increase its anticancer activity via synergistic chemo-photodynamic effect. The drug delivery applications of ZnONPs with special emphasis on drug loading mechanism, stimuli-responsive controlled release and therapeutic effects have also been discussed in this review. Finally, its side effects to vital body organs with mechanism via different exposure routes, the future direction of the ZnONPs research and application are also discussed.
Asunto(s)
Salud , Nanopartículas , Óxido de Zinc/química , Óxido de Zinc/farmacología , Antineoplásicos/efectos adversos , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Técnicas de Química Sintética , Portadores de Fármacos/efectos adversos , Portadores de Fármacos/síntesis química , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Humanos , Riesgo , Óxido de Zinc/efectos adversosRESUMEN
Prosthesis-associated infections and aseptic loosening are major causes of implant failure. There is an urgent need to improve the antibacterial ability and osseointegration of orthopedic implants. Zinc oxide nanoparticles (ZnO-NPs) are a common type of zinc-containing metal oxide nanoparticles that have been widely studied in many fields, such as food packaging, pollution treatment, and biomedicine. The ZnO-NPs have low toxicity and good biological functions, as well as antibacterial, anticancer, and osteogenic capabilities. Furthermore, ZnO-NPs can be easily obtained through various methods. Among them, green preparation methods can improve the bioactivity of ZnO-NPs and strengthen their potential application in the biological field. This review discusses the antibacterial abilities of ZnO-NPs, including mechanisms and influencing factors. The toxicity and shortcomings of anticancer applications are summarized. Furthermore, osteogenic mechanisms and synergy with other materials are introduced. Green preparation methods are also briefly reviewed.
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Antibacterianos/farmacología , Nanopartículas del Metal/química , Osteogénesis/efectos de los fármacos , Óxido de Zinc/farmacología , Animales , Antibacterianos/química , Antineoplásicos/efectos adversos , Antineoplásicos/química , Antineoplásicos/farmacología , Condrogénesis/efectos de los fármacos , Tecnología Química Verde , Humanos , Nanopartículas del Metal/efectos adversos , Nanopartículas del Metal/uso terapéutico , Osteogénesis/fisiología , Prótesis e Implantes , Óxido de Zinc/efectos adversos , Óxido de Zinc/toxicidadRESUMEN
Zinc oxide nanoparticles (ZnONPs) are frequently encountered nanomaterials in our daily lives. Despite the benefits of ZnONPs in a variety of applications, many studies have shown potential health hazards of exposure to ZnONPs. We have shown that oropharyngeal aspiration of ZnONPs in mice increases lung inflammation. However, the detailed mechanisms underlying pulmonary inflammatory cell infiltration remain to be elucidated. Endothelium functions as a barrier between the blood stream and the blood vessel wall. Endothelial barrier dysfunction may increase infiltration of immune cells into the vessel wall and underlying tissues. This current study examined the effects of ZnONPs exposure on endothelial barriers. ZnONPs exposure increased leukocyte infiltration in the mouse lungs. In endothelial cells, ZnONPs reduced the continuity of tight junction proteins claudin-5 and zonula occludens-1 (ZO-1) at the cell junctions. ZnONPs induced adherens junction protein VE-cadherin internalization from membrane to cytosol and dissociation with ß-catenin, leading to reduced and diffused staining of VE-cadherin and ß-catenin at cell junctions. Our results demonstrated that ZnONPs disrupted both tight and adherens junctions, compromising the integrity and stability of the junction network, leading to inflammatory cell infiltration. Thus, ZnONPs exposure in many different settings should be carefully evaluated for vascular effects and subsequent health impacts.
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Claudina-5/genética , Endotelio/efectos de los fármacos , Neumonía/genética , Óxido de Zinc/efectos adversos , Proteína de la Zonula Occludens-1/genética , Uniones Adherentes/efectos de los fármacos , Uniones Adherentes/genética , Animales , Vasos Sanguíneos/efectos de los fármacos , Humanos , Leucocitos/efectos de los fármacos , Ratones , Nanopartículas/efectos adversos , Orofaringe/efectos de los fármacos , Neumonía/inducido químicamente , Neumonía/patologíaRESUMEN
Zinc Oxide Nanoparticles (ZnO NPs) are a type of metal oxide nanoparticle with an extensive use in biomedicine. Several studies have focused on the biosafety of ZnO NPs, since their size and surface area favor entrance and accumulation in the body, which can induce toxic effects. In previous studies, ZnO NPs have been identified as a dose- and time-dependent cytotoxic inducer in testis and male germ cells. However, the consequences for the first cell stage of spermatogenesis, spermatogonia, have never been evaluated. Therefore, the aim of the present work is to evaluate in vitro the cytotoxic effects of ZnO NPs in spermatogonia cells, focusing on changes in cytoskeleton and nucleoskeleton. For that purpose, GC-1 cell line derived from mouse testes was selected as a model of spermatogenesis. These cells were treated with different doses of ZnO NPs for 6 h and 12 h. The impact of GC-1 cells exposure to ZnO NPs on cell viability, cell damage, and cytoskeleton and nucleoskeleton dynamics was assessed. Our results clearly indicate that higher concentrations of ZnO NPs have a cytotoxic effect in GC-1 cells, leading to an increase of intracellular Reactive Oxygen Species (ROS) levels, DNA damage, cytoskeleton and nucleoskeleton dynamics alterations, and consequently cell death. In conclusion, it is here reported for the first time that ZnO NPs induce cytotoxic effects, including changes in cytoskeleton and nucleoskeleton in mouse spermatogonia cells, which may compromise the progression of spermatogenesis in a time- and dose-dependent manner.
Asunto(s)
Nanopartículas del Metal/toxicidad , Espermatogonias/efectos de los fármacos , Óxido de Zinc/toxicidad , Animales , Muerte Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Daño del ADN/fisiología , Masculino , Ratones , Especies Reactivas de Oxígeno/metabolismo , Espermatogénesis/efectos de los fármacos , Espermatogonias/metabolismo , Óxido de Zinc/efectos adversosRESUMEN
Cancer is the leading cause of death and exhausts human and economic resources for treatment and protection. Zinc oxide nanoparticles play an effective role in tumor treatment but with some cautions, such as overexpression of cytochrome P450, hepatic overload, and the mammalian target of rapamycin pathway resistance. Although lanthanides have antitumor activity, their use is limited. Therefore, the current study aims to improve the effectiveness of zinc oxide nanoparticle via doping with lanthanides, such as samarium. In vitro study revealed that samarium doped with zinc oxide showed more antitumor activity than the other lanthanides, and the antitumor activity depends on the concentration of samarium in the nanocomposite. The in vivo experiment on mice bearing Ehrlich solid tumor revealed that intramuscular injection of samarium/zinc oxide downregulates the expressions of CXCR4 and PI3K/Akt/mammalian target of rapamycin pathway in respect to Ehrlich solid tumor group. Regarding the apoptotic biomarkers, samarium/zinc oxide upregulates the apoptotic biomarker; Bax accompanied with the mitotic catastrophe which was indicated by cell cycle arrest in G2 phase. Moreover, samarium:zinc oxide nanoparticles exhibited minimum toxicity which was indicated by suppressed activities of cytochrome P450 and hepatic enzymes, including alanine transaminase and aspartate transaminase. In addition, the histopathological finding, as well as immunophenotyping results, appreciated the biochemical finding. Therefore, samarium:zinc oxide might be offered a new approach to improve the effectiveness of zinc oxide nanoparticles along with lower toxic effect. Also, samarium:zinc oxide nanoparticles can be a candidate as a new antitumor compound to detect its mode of action.
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Antineoplásicos/farmacología , Inhibidores Enzimáticos del Citocromo P-450/farmacología , Receptores CXCR4/antagonistas & inhibidores , Samario/farmacología , Óxido de Zinc/farmacología , Animales , Regulación hacia Abajo , Femenino , Ratones , Nanopartículas , Receptores CXCR4/genética , Samario/efectos adversos , Óxido de Zinc/efectos adversosAsunto(s)
Nanopartículas/administración & dosificación , Absorción Cutánea/efectos de los fármacos , Piel/metabolismo , Protectores Solares/farmacocinética , Óxido de Zinc/farmacocinética , Adulto , Baños , Membrana Celular/efectos de los fármacos , Seguridad de Productos para el Consumidor , Voluntarios Sanos , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Nanopartículas/efectos adversos , Piel/citología , Piel/efectos de los fármacos , Protectores Solares/administración & dosificación , Protectores Solares/efectos adversos , Natación , Adulto Joven , Óxido de Zinc/administración & dosificación , Óxido de Zinc/efectos adversosRESUMEN
Inhalation of high concentrations of zinc oxide (ZnO) particles may cause metal fume fever. A useful tool to characterize the reactivity of innate immune cells of an individual, e.g., after in vivo exposure, is the whole blood assay (WBA). The measurable outcome of WBA is the release of cytokines, especially pro-inflammatory and pyrogenic cytokines induced by stimulation in vitro. The aim of the study was to evaluate whether inhalation of nano-sized zinc oxide particles modifies the results of WBA from healthy blood donors. Sixteen healthy subjects were exposed to filtered air and ZnO particles (0.5, 1.0, and 2.0 mg/m3) for 4 h on four different days. Blood was collected before and 24 h after exposure, and ex vivo stimulation of the whole blood was performed using different endotoxin concentrations. The release of interleukin (IL)-1ß and IL-8 after 22-h incubation was quantified with specific immunoassays. The dose-response relationship of ex vivo stimulation with different endotoxin concentrations was not affected by previous ZnO exposure. However, based on the previously established calculation models, changes due to ZnO exposure could be described. The range of cytokine release in WBA was calculated for the whole group of blood donors, for the subgroups of low and high responders (each n = 8), and on the individual level. Most changes were observed after 0.5 mg/m3 ZnO exposure. Higher ZnO exposure did not yield higher effects. We conclude that the effects of inhalation of nano-sized ZnO particles in blood of healthy donors using the WBA could be determined. However, it should be noted that cytokine release as outcome of WBA is not a marker of disease.
Asunto(s)
Análisis Químico de la Sangre , Inmunidad Innata/efectos de los fármacos , Inmunidad Innata/inmunología , Óxido de Zinc/efectos adversos , Citocinas/sangre , Citocinas/inmunología , Endotoxinas/sangre , Humanos , Óxido de Zinc/administración & dosificaciónRESUMEN
The unclear bio-safety issue and potential risk of nanoparticles (NPs) on various organelles can be considered as a major challenge. In the present study, we have assessed the green synthesis of ZnO nanoparticles using Hyssop (Hyssopus officinalis) extract and their effects on PC3 cell line and BALB/c mice model. The cytotoxicity of the ZnO-NPs was assessed on PC3 cell line by MTT test after characterisation. Apoptotic effect of ZnO-NPs was determined by in vitro AO/PI staining. The histopathological assessments and determination of LH and FSH levels carried out as in vivo analysis in BALB/c adult male mice. The expression of major genes involved in spermatogenesis and sperm maturation (Adam3, Prm1, Spata19, Tnp2, Gpx5) were also analysed. The obtained result demonstrated that the IC50 for PC3 cell line treated with green-synthesised ZnO-NPs during 24 and 48 hr was reported 8.07 and 5 µg/ml respectively. Meanwhile, the induced apoptosis was recorded 26.6% ± 0.05, 44% ± 0.12 and 80% ± 0.07 of PC3 cells. The results of gene expression analysis revealed that the increase in the concentration of ZnO-NPs significantly (p < .05) down-regulated the Adam3, Prm1, Spata-19, Tnp2 and Gpx5 genes. The overall results of this research elucidated that ZnO-NPs impaired spermatogenesis, sperm maturation process and sperm motility.
Asunto(s)
Nanopartículas del Metal/efectos adversos , Neoplasias de la Próstata/tratamiento farmacológico , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Óxido de Zinc/efectos adversos , Administración Oral , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Tecnología Química Verde/métodos , Humanos , Hyssopus/química , Concentración 50 Inhibidora , Masculino , Nanopartículas del Metal/administración & dosificación , Nanopartículas del Metal/química , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/química , Hojas de la Planta/química , Próstata/citología , Próstata/efectos de los fármacos , Neoplasias de la Próstata/patología , Motilidad Espermática/efectos de los fármacos , Testículo/patología , Pruebas de Toxicidad Subaguda , Óxido de Zinc/administración & dosificación , Óxido de Zinc/síntesis químicaRESUMEN
High aspect ratio zinc oxide nanowires (ZnONWs) have become one of the most important products in nanotechnology. The wide range applications of ZnONWs have heightened the need for evaluating the risks and biological consequences to these particles. In this study, we investigated inflammatory pathways activated by ZnONWs in cultured cells as well as the consequences of systemic exposure in mouse models. Confocal microscopy showed rapid phagocytic uptake of FITC-ZnONWs by macrophages. Exposure of macrophages or lung epithelial cells to ZnONWs induced the production of CCL2 and CCL11. Moreover, ZnONWs exposure induced both IL-6 and TNF-α production only in macrophages but not in LKR13 cells. Intratracheal instillation of ZnONWs in C57BL/6 mice induced a significant increase in the total numbers of immune cells in the broncho alveolar lavage fluid (BALFs) 2 days after instillation. Macrophages and eosinophils were the predominant cellular infiltrates of ZnONWs exposed mouse lungs. Similar cellular infiltrates were also observed in a mouse air-pouch model. Pro-inflammatory cytokines IL-6 and TNF-α as well as chemokines CCL11, and CCL2 were increased both in BALFs and air-pouch lavage fluids. These results suggest that exposure to ZnONWs may induce distinct inflammatory responses through phagocytic uptake and formation of soluble Zn2+ ions.
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Quimiocina CCL11/inmunología , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunología , Inflamación/etiología , Nanocables/efectos adversos , Óxido de Zinc/efectos adversos , Animales , Quimiocina CCL11/genética , Quimiocina CCL2/genética , Modelos Animales de Enfermedad , Técnicas In Vitro , Inflamación/genética , Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Interleucina-6/genética , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Nanocables/química , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Células RAW 264.7 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/genética , Regulación hacia Arriba/efectos de los fármacos , Óxido de Zinc/químicaRESUMEN
PURPOSE: The aim of this study was to evaluate the adverse effects of ZnO NPs on male reproductive system and explore the possible mechanism. METHODS: In this study, the effect of oral administration of 50, 150 and 450 mg/kg zinc oxide nanoparticles (ZnO NPs) in adult male mice was studied over a 14-day period. RESULTS: The results showed that the number of sperms in the epididymis and the concentration of testosterone in serum were decreased with an increased dose of ZnO NPs. Testicular histopathological lesions like detachment, atrophy and vacuolization of germ cells were observed. The results showed that increased dosage of ZnO NPs correspondingly up-regulated the IRE1α, XBP1s, BIP, and CHOP (P<0.05) which are genes related to ER stress. These observations indicated that ZnO NPs had adverse effects on the male reproductive system in a dose-dependent manner possibly through ER stress. The expression of caspase-3 was significantly increased in all the treated groups (P<0.001), which reflected the possible activation of apoptosis. Additionally, there was significant down-regulation of the gene StAR (P<0.05), a key player in testosterone synthesis. When an ER-stress inhibitor salubrinal was administered to the 450 mg/kg ZnO NPs treatment group, the damages to the seminiferous tube and vacuolization of Sertoli and Leydig cells were not observed. Furthermore, the testosterone levels in the serum were similar to the control group after the subsequent salubrinal treatment. CONCLUSION: It may be inferred that the ZnO NP's reproductive toxicity in male mice occurred via apoptosis and ER-stress signaling pathway.
Asunto(s)
Estrés del Retículo Endoplásmico/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Testículo/efectos de los fármacos , Óxido de Zinc/toxicidad , Animales , Apoptosis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Estrés del Retículo Endoplásmico/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Células Intersticiales del Testículo/efectos de los fármacos , Masculino , Nanopartículas del Metal/administración & dosificación , Nanopartículas del Metal/efectos adversos , Ratones , Células de Sertoli/efectos de los fármacos , Células de Sertoli/patología , Transducción de Señal/efectos de los fármacos , Recuento de Espermatozoides , Testículo/metabolismo , Testículo/patología , Testosterona/sangre , Zinc/farmacocinética , Óxido de Zinc/administración & dosificación , Óxido de Zinc/efectos adversosRESUMEN
Zinc oxide nanoparticles (ZnO NPs) have shown adverse health impact on the human male reproductive system, with evidence of inducing apoptosis. However, whether or not ZnO NPs could promote autophagy, and the possible role of autophagy in the progress of apoptosis, remain unclear. In the current study, in vitro and in vivo toxicological responses of ZnO NPs were explored by using a mouse model and mouse Leydig cell line. It was found that intragastrical exposure of ZnO NPs to mice for 28 days at the concentrations of 100, 200, and 400 mg/kg/day disrupted the seminiferous epithelium of the testis and decreased the sperm density in the epididymis. Furthermore, serum testosterone levels were markedly reduced. The induction of apoptosis and autophagy in the testis tissues was disclosed by up-regulating the protein levels of cleaved Caspase-8, cleaved Caspase-3, Bax, LC3-II, Atg 5, and Beclin 1, accompanied by down-regulation of Bcl 2. In vitro tests showed that ZnO NPs could induce apoptosis and autophagy with the generation of oxidative stress. Specific inhibition of autophagy pathway significantly decreased the cell viability and up-regulated the apoptosis level in mouse Leydig TM3 cells. In summary, ZnO NPs can induce apoptosis and autophagy via oxidative stress, and autophagy might play a protective role in ZnO NPs-induced apoptosis of mouse Leydig cells.