Renal histological alterations induced by acute exposure of titanium dioxide nanoparticles / Alteraciones histológicas renales inducidas por la exposición aguda de nanopartículas de dióxido de titanio

SUMMARY: Titanium dioxide nanoparticles (TiO2 NPs) are widely used in many commercial products, nanomedicine, agriculture, personal care products, different industries and pharmaceutical preparations with potential risk in human health and the environment. The current work was conducted to investigate the renal damage that might be induced by the acute toxicity TiO2 NPs. A total of 40 healthy male adult Wistar albino rats (Rattus norvegicus) were exposed to TiO2 NPs (126, 252, 378 mg/kg bw) for 24 and 48 h. Fresh portions of the kidneys from each rat were processed for histological and histochemical alterations. In comparison with respective control rats, exposure to TiO2 NPs has marked the following glomerular, tubular and interstitial alterations including the followings: glomerular congestion, Bowman's capsule swelling and dilatation, inflamed glomeruli, renal tubules cloudy swelling, karyorrhexis, karyolysis, infiltration of inflammatory cells, congestion, necrosis, hydropic degeneration, dilatation and congestion of blood vessels, hyaline droplets and hyaline casts precipitation, interstitial edema and fibrosis. From the findings of the current work one may conclude that TiO2 NPs are capable of inducing kidney damage with more insulation in the cortex and the proximal convoluted tubules than the medulla and the distal ones respectively. In addition, it might be concluded that renal damage induced by these nanomaterials is dose and duration of exposure dependent. Further hematological, biochemical, immunohistochemical, and ultra-structural studies are recommended.

RESUMEN: Las nanopartículas de dióxido de titanio (TiO2 NP) se usan ampliamente en muchos productos comerciales, nanomedicina, agricultura, productos para el cuidado personal, diferentes industrias y preparaciones farmacéuticas con riesgo potencial para la salud humana y el medio ambiente. El trabajo actual se realizó para investigar el daño renal que podría ser inducido por la toxicidad aguda NP de TiO2. Un total de 40 ratas Wistar albinas adultas sanas (Rattus norvegicus) fueron expuestas a TiO2 NP (126, 252, 378 mg / kg de peso corporal) durante 24 y 48 h. Las muestras de los riñones de las ratas se procesaron para estudios histológicos e histoquímicos. En comparación con las ratas control, la exposición de las ratas a TiO2 NP presentaron las siguientes alteraciones glomerulares, tubulares e intersticiales: congestión glomerular, dilatación de la cápsula de Bowman, inflamación glomerular, túbulos renales aumentados, cariorrexis, cariólisis, infiltración de células inflamatorias, congestión, necrosis, degeneración hidrópica, dilatación y congestión de vasos sanguíneos, gotas y precipitaciones hialina, edema intersticial y fibrosis. A partir de los hallazgos del trabajo actual, se puede concluir que las NP de TiO 2 son capaces de inducir daño renal con más aislamiento en la corteza y en los túbulos contorneados proximales que en la médula y los túbulos contorneados distales, respectivamente. Además, se podría concluir que el daño renal inducido por estos nanomateriales depende de la dosis y la duración de la exposición. Se recomiendan estudios adicionales hematológicos, bioquímicos, inmunohistoquímicos y ultraestructurales.

Biosynthesis of gold nanoparticles by two bacterial and fungal strains, Bacillus cereus and Fusarium oxysporum, and assessment and comparison of their nanotoxicity in vitro by direct and indirect assays

Background: Although nanoparticles (NPs) have many advantages, it has been proved that they may be absorbed by and have toxic effects on the human body. Recent research has tried to evaluate and compare the nanotoxicity of gold nanoparticles (AuNPs) produced by two types of microorganisms in vitro by two different methods. AuNPs were produced by Bacillus cereus and Fusarium oxysporum, and their production was confirmed by visible spectral, transmission electron microscope, and X-ray diffraction (XRD) analyses. The human fibroblast cell line CIRC-HLF was treated with AuNPs, and the induced nanotoxicity was measured using direct microscopic and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results: The results showed that the produced AuNPs had a maximum absorbance peak around 510­530 nanometer (nm), with spherical, hexagonal, and octagonal shapes and average sizes around 20­50 nm. The XRD results confirmed the presence of GNPs in the microbial culture supernatants. An MTT assay showed that GNPs had dose-dependent toxic effects, and microscopic analysis showed that GNPs induced cell abnormalities in doses lower than the determined half-maximal inhibitory concentrations (IC50s). Conclusions: In conclusion, the biologically produced AuNPs had toxic effects in the cell culture, and direct techniques such as microscopic evaluation instead of indirect methods such as MTT assay were more useful for assessing the nanotoxicity of the biologically produced AuNPs. Thus, the use of only MTT assay for nanotoxicity evaluation of AuNPs is not desirable.

Cobalt oxide nanoparticles aggravate DNA damage and cell death in eggplant via mitochondrial swelling and NO signaling pathway

BACKGROUND: Despite manifold benefits of nanoparticles (NPs), less information on the risks of NPs to human health and environment has been studied. Cobalt oxide nanoparticles (Co3O4-NPs) have been reported to cause toxicity in several organisms. In this study, we have investigated the role of Co3O4-NPs in inducing phytotoxicity, cellular DNA damage and apoptosis in eggplant (Solanum melongena L. cv. Violetta lunga 2). To the best of our knowledge, this is the first report on Co3O4-NPs showing phytotoxicity in eggplant. RESULTS: The data revealed that eggplant seeds treated with Co3O4-NPs for 2 h at a concentration of 1.0 mg/ml retarded root length by 81.5 % upon 7 days incubation in a moist chamber. Ultrastructural analysis by transmission electron microscopy (TEM) demonstrated the uptake and translocation of Co3O4-NPs into the cytoplasm. Intracellular presence of Co3O4-NPs triggered subcellular changes such as degeneration of mitochondrial cristae, abundance of peroxisomes and excessive vacuolization. Flow cytometric analysis of Co3O4-NPs (1.0 mg/ml) treated root protoplasts revealed 157, 282 and 178 % increase in reactive oxygen species (ROS), membrane potential (APm) and nitric oxide (NO), respectively. Besides, the esterase activity in treated protoplasts was also found compromised. About 2.4-fold greater level of DNA damage, as compared to untreated control was observed in Comet assay, and 73.2 % of Co3O4-NPs treated cells appeared apoptotic in flow cytometry based cell cycle analysis. CONCLUSION: This study demonstrate the phytotoxic potential of Co3O4-NPs in terms of reduction in seed germination, root growth, greater level of DNA and mitochondrial damage, oxidative stress and cell death in eggplant. The data generated from this study will provide a strong background to draw attention on Co3O4-NPs environmental hazards to vegetable crops.

Toxicidade do peróxido de carbamida 16% adicionado de nanopartículas de hidroxiapatita / Carbamide peroxide toxicity added 16% hydroxyapatite nanoparticles

O clareamento dental é um dos tratamentos mais realizados nos consultórios odontológicos a fim de melhorar a aparência do sorriso. O procedimento consiste na aplicação de um gel clareador, a base de peróxido de carbamida ou de hidrogênio, sobre os dentes a serem clareados. A sensibilidade dentária é o efeito adverso mais frequentemente relatado no clareamento dentário e é a principal causa de desmotivação dos pacientes. O mecanismo pelo qual se produz a sensibilidade após clareamento dentário ainda não foi completamente elucidado; no entanto, parece estar associado à rápida difusão dos agentes clareadores através do esmalte e dentina que, devido ao seu grau de citotoxicidade, podem agir agredindo as células pulpares, causando sensibilidade. O objetivo deste estudo foi avaliar a biocompatibilidade de nanopartícula de hidroxiapatita adicionada ao gel clareador peróxido de carbamida 16% com flúor e sem flúor e, para tanto, foram realizados testes de citotoxidade empregando MTT. Como resultados verificou-se que as nanopartículas de hidroxiapatita, quando comparadas aos géis de peróxido de carbamida a 16% com e sem flúor, foram as menos citotóxicas (p< 0.05). As diluições citotóxicas convertidas para 70% das amostras testadas também foram comparadas através do teste de Anova com tukey. Foi possível observar que as partículas de nanoHap quando adicionadas nos géis de clareamento com e sem flúor reduziu significativamento a citotoxidade. Concluímos que o novo material proposto nesta investigação apresenta melhor biocompatibilidade do que o gel sem hidroxiapatita, acompanhado da redução da citotoxidade, tais aspectos sugerem que as nanopartículas de hidroxiapatita podem ter aplicações clínicas futuras em tecidos mineralizados em procedimentos de clareamento dental, contribuindo para a redução da sensibilidade dentária.

The dental bleaching is one of the most procedures performed at dental offices to improve the appearance of the smile. The procedure consists of the application of a bleching gel, based on carbamide peroxide or hydrogen over the teeth to be whitened. Tooth sensibility is the frequently reported adverse effect on tooth whitening and is the leading cause of demotivation by the patients. The mechanism that provides the sensibility after tooth whitening has not already been fully elucidated; however, it appears to be associated with the rapid diffusion of bleaching agents through the enamel and dentin that, because of their degree of cytotoxicity, may act attacking pulp cells, causing the sensibility. The aim of this study was to evaluate the biocompatibility of hydroxyapatite nanoparticles added to whitening gel of 16% carbamide peroxide with and without fluoride and, therefore, cytotoxicity tests were performed using MTT. As a result, it was found that the hydroxyapatite nanoparticles, compared to the gels of 16 % carbamide peroxide with and without fluoride, were less cytotoxic (p <0.05). Cytotoxic dilutions converted to 70 % of the tested samples were compared using ANOVA test with Tukey. We concluded that the new material proposed in this research has a better biocompatibility in comparison with the gel without hydroxyapatite, followed by a reduction of cytotoxicity. These aspects suggest that the hydroxyapatite nanoparticles may have clinical future applications in mineralized tissues when dental bleaching procedures are performed, contributing to the reduction of tooth sensitivity. We conclude that the new material proposed in this research has a better biocompatibility of the gel without hydroxyapatite, accompanied by a reduction of cytotoxicity, these aspects suggest that the hydroxyapatite nanoparticles may have future clinical applications in mineralized tissues in dental bleaching procedures, contributing to a reduction tooth sensitivity.

Insulin-like growth factor (IgF)-I, IgF binding protein-3, and prostate cancer: correlation with gleason score

Introduction Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa). Objective This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH). Materials and Methods This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups. Results PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p<0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p<0.001) and at the inclusion in the study (p<0.001) and IGFBP3 (0.016) among patients with Gleason <7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason <7 and ≥7. Conclusions Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients. .

Prophylactic role of B vitamins against bulk and zinc oxide nanoparticles toxicity induced oxidative DNA damage and apoptosis in rat livers

The aim of this work is to explore the protective of B vitamins [B[3], B[6] and B[12]] against the hepatotoxic potency of either bulk zinc oxide [ZnO-bulk] or its nanoparticles [ZnO-NPs]-induced liver damage in rats. ZnO- bulk or its NPs were administered orally [500 mg/kg b.w.] for 10 successive days. The results revealed that oral coadministration of combination of B vitamins [250 mg B[3], 60 mg B[6] and 0.6 mg B[12] /Kg body weight] daily for 3 weeks to rats intoxicated by either ZnO- bulk or its NPs markedly ameliorated increases in serum of alanine aminotransferase [ALT], aspartate aminotransferase [AST] and lactate dehdrogenase [LDH]. The B vitamins also down-regulated increases in serum glucose level as well as increases in immuno-inflammatory biomarkers, including tumor necrosis factor- alpha [TNF- alpha] and C-reactive protein compared with intoxicated, untreated rats. Beside, the used agent successfully modulated the alterations in serum vascular endothelial growth factor [VEGF], attenuated liver oxidative DNA damage compared with ZnO intoxicated groups. We showed that the used B complex mitigated increased malondialdehyde [MDA], decrease in glutathione peroxidase [GPx] and increase in the apoptosis marker caspase 3 of liver tissue in response to either ZnO-bulk or its NP toxicity. In conclusion, early treatment with vitamin B complex may protect liver tissue from deleterious damage induced by the toxic effects of ZnO- bulk or its NPs

Radiopacity and cytotoxicity of Portland cement associated with niobium oxide micro and nanoparticles

Objective Mineral Trioxide Aggregate (MTA) is composed of Portland Cement (PC) and bismuth oxide (BO). Replacing BO for niobium oxide (NbO) microparticles (Nbµ) or nanoparticles (Nbη) may improve radiopacity and bioactivity. The aim of this study was to evaluate the radiopacity and cytotoxicity of the materials: 1) PC; 2) White MTA; 3) PC+30% Nbµ; 4) PC+30% Nbη. Material and Methods For the radiopacity test, specimens of the different materials were radiographed along an aluminum step-wedge. For cell culture assays, Saos-2 osteoblastic-cells (ATCC HTB-85) were used. Cell viability was evaluated through MTT assay, and bioactivity was assessed by alkaline phosphatase activity assay. Results The results demonstrated higher radiopacity for MTA, followed by Nbµ and Nbη, which had similar values. Cell culture analysis showed that PC and PC+NbO associations promoted greater cell viability than MTA. Conclusions It was concluded that the combination of PC+NbO is a potential alternative for composition of MTA. .

Estudio exploratorio de higiene industrial en ambientes de trabajo donde se producen o utilizan nanopartículas / Exploratory study of industrial hygiene in work areas where nanoparticles are produced or used

Se realizó un estudio exploratorio con los objetivos de identificar empresas que produzcan o manipulen nanopartículas en Chile, evaluar los riesgos para la salud de estas actividades y entregar recomendaciones para su control. Se encontró que la nanotecnología está en una etapa incipiente, con un reducido número de aplicaciones en procesos industriales, concentrándose el desarrollo y aplicación principalmente en centros de investigación de las universidades, donde los investigadores y estudiantes son el principal grupo de potenciales expuestos. Para evaluar la exposición en las empresas e instituciones identificadas, se utilizó un método cualitativo simplificado y un método cuantitativo que se basa en las técnicas tradicionales de higiene ocupacional complementadas con la caracterización de las nanopartículas mediante microscopía electrónica. Se evalúa la exposición a nanopartículas de cobre, carbonato de calcio y partículas ultrafinas de humos de soldadura. La metodología de evaluación cualitativa, si bien requiere algún grado de acondicionamiento, demostró ser una herramienta particularmente útil para definir sistemas de protección en el caso de las nanopartículas, cuya toxicidad es incierta y de las cuales no se tienen establecidas técnicas de medición ni límites permisibles. Los métodos de medición tradicionales de la higiene industrial no entregan la información suficiente para evaluar la exposición, debiendo ser complementados con microscopía electrónica para caracterizar el tamaño y composición química, parámetros claves en la toxicidad de las nanopartículas. El trabajo realizado entrega una base de información y conocimiento a nivel exploratorio, que se estima útil para evaluar el riesgo de exposición en aplicaciones que pudieran surgir en el contexto actual del desarrollo de la nanotecnología en nuestro país.

An exploratory research was developed in order to identify companies which produce or handle nanoparticles in Chile, evaluate the risks for health from these activities and give suggestions for controlling them. It was found that nanotechnology is in an incipient stage, with a reduced numbers of applications in industrial processes, focusing the development and application mainly on research centers in Universities, where researchers and students are the main exposed potential groups. To evaluate the exposure in identified companies and institutions, it was used a qualitative simplified method and a quantitative method which is based in traditional technique of occupational hygiene complemented by the characterization of nanoparticles with electronic microscopy. It was evaluated the exposure to nanoparticles of copper, calcium carbonate and welding smoke ultrafine particles. The methodology of qualitative evaluation, although requires some degree of conditioning, showed being a especially useful tool to define protection systems in nanoparticles case, whose toxicity is uncertain and we do not have established techniques of measuring them or permissible limits. Traditional measuring methods of industrial hygiene do not bring enough information to evaluate the exposure, and they must be complemented with electronic microscopy to characterize the size and chemical composition, key parameters in nanoparticles toxicity. This work provides a base of information and knowledge in a exploratory level, which is estimated as a useful tool to evaluate the exposure risk in applications that may appear in the current nanotechnology development in our country.

Toxicity study of silver nanoparticles synthesized from suaeda monoica on Hep-2 cell line

Recently there has been fabulous excitement in the nano-biotechnological area for the study of nanoparticles synthesis using some natural biological system, which has led the growth advanced nanomaterials. This intention made us to assess the biologically synthesized silver nanoparticles from the leaf of Suaeda monoica [S.monoica] using 1 mM silver nitrate. The leaf extract of S.monoica incubated with 1 mM silver nitrate solution and characterized by UV-spectrometer and AFM. The effect of synthesized silver nanoparticles on Human Epidermoid Larynx Carcinoma cell line was evaluated by the MTT colorimetric technique. As a result we observed gradual change in the colour of extract from greenish to brown. The synthesized silver nanoparticles con-firmed by UV at 430 nm and spherical shape identified in the range of 31 nm under AFM. The effect of silver nanoparticles on Human Epidermoid Larynx Carcinoma cell line exhibits a dose-dependent toxicity for the cell tested and the viability of Hep-2 cells decreased to 50% [IC50] at the concentration of 500 nM. Further findings will be determined the exact mechanisms of this cost effective Nano-treatments

Ultrastructural analyses of platelets and fibrin networks in BALB/c mice after inhalation of spherical and rod-shaped titanium nanoparticles / Análisis ultraestructural de plaquetas y redes de fibrina en ratones BALB/c después de la inhalación de nanopartículas de titanio con forma esférica y de barra

Engineered nanoparticles are designed to perform specific functions and therefore have specific properties that could potentially be harmful. Nanoparticles such as titanium dioxide have the potential to become transparent and are therefore widely used in cosmetic products and sunscreen. Research on the toxicity of nanoparticles is of utmost importance and numerous in vitro studies have shown that some of these particles could have adverse health effects. The current study aimed to investigate the in vivo effects of two different titanium nanoparticles at two different concentrations after inhalation by experimental BALB/c mice. This was done to determine whether these particles will cause an inflammatory reaction, visible as alterations in platelet and fibrin ultrastructure. Mice were divided into five experimental groups comprising of a control group, high and low concentration groups exposed to the spherical-shaped particles, as well as high and low concentration groups exposed to the rod-shaped particles. The ultrastructure of the fibrin networks and platelet aggregates of these experimental groups were investigated and compared to that of controls. Results indicated that the fibrin networks of the exposed animals have a net-like covering over the major fibres, typical to that found in animals with inflammation. It can therefore be concluded that the nanoparticles used in this study may have the potential to cause an inflammatory reaction, affecting the haemostatic physiology.

Las nanopartículas han sido diseñadas para realizar funciones específicas, y por lo tanto, tienen propiedades específicas que podrían ser perjudiciales. Las nanopartículas, como el dióxido de titanio tienen el potencial de llegar a ser transparentes, pudiendo ser ampliamente utilizadas en productos cosméticos y protectores solares. La investigación sobre la toxicidad de las nanopartículas es de suma importancia y numerosos estudios in vitro han demostrado que algunas de estas partículas, podrían tener efectos adversos para la salud. El presente estudio tuvo como objetivo investigar los efectos in vivo de dos nanopartículas de titanio diferentes en dos concentraciones después de la inhalación experimental de ratones BALB/c. Esto se realizó para determinar si las partículas provocan una reacción inflamatoria, visible como alteraciones en la ultraestructura de plaquetas y fibrina. Los ratones se dividieron en cinco grupos experimentales, que comprende un grupo control y grupos expuestos a nanopartículas de forma esférica de alta y baja concentración, así como grupos expuestos a nanopartículas en forma de barra de alta y baja concentración. Fueron investigadas la ultraestructura de las redes de fibrina y agregados plaquetarios de estos grupos experimentales y se comparó con la de los controles. Los resultados indicaron que en los animales expuestos se observó una red de fibrina que recubría las fibras más grandes, típicas de las que se encuentran en los animales con inflamación. Por lo tanto, puede concluirse que las nanopartículas utilizadas en este estudio pueden tener el potencial de causar una reacción inflamatoria, afectando a la fisiología hemostática.

Nanoparticles-A Thoracic Toxicology Perspective

A substantial literature demonstrates that the main ultrafine particles found in ambient urban air are combustion-derived nanoparticles (CDNP) which originate from a number of sources and pose a hazard to the lungs. For CDNP, three properties appear important-surface area, organics and metals. All of these can generate free radicals and so induce oxidative stress and inflammation. Inflammation is a process involved in the diseases exhibited by the individuals susceptible to the effects of PM- development and exacerbations of airways disease and cardiovascular disease. It is therefore possible to implicate CDNP in the common adverse effects of increased PM. The adverse effects of increases in PM on the cardiovascular system are well-documented in the epidemiological literature and, as argued above, these effects are likely to be driven by the combustion-derived NP. The epidemiological findings can be explained in a number of hypotheses regarding the action of NP:-1) Inflammation in the lungs caused by NP causes atheromatous plaque development and destabilization; 2) The inflammation in the lungs causes alteration in the clotting status or fibrinolytic balance favouring thrombogenesis; 3) The NP themselves or metals/organics released by the particles enter the circulation and have direct effects on the endothelium, plaques, the clotting system or the autonomic nervous system/ heart rhythm. Environmental nanoparticles are accidentally produced but they provide a toxicological model for a new class of purposely 'engineered' NP arising from the nanotechnology industry, whose effects are much less understood. Bridging our toxicological knowledge between the environmental nanoparticles and the new engineered nanoparticles is a considerable challenge.