Oxidative stress contributes to silica nanoparticle-induced cytotoxicity in human embryonic kidney cells

In order to elucidate the nanoparticle-induced cytotoxicity and its mechanism, the effects of 20 and 50 nm silica nanoparticles on cultured human embryonic kidney (HEK293) cells were investigated. Cell viability, mitochondrial function, cell morphology, reactive oxygen species (ROS), glutathione (GSH), thiobarbituric acid reactive substance (TBARS), cell cycle and apoptosis were assessed under control and silica exposed conditions. Exposure to 20 or 50 nm SiO₂ nanoparticles at dosage levels between 20 and 100 μg/ml decreased cell viability in a dose-dependent manner. Median lethal dose (LD₅₀) of 24 h exposure was 80.2 ± 6.4 and 140.3 ± 8.6 μg/ml for 20 and 50 nm SiO₂ nanoparticles, respectively. Morphological examination revealed cell shrinkage and nuclear condensation after SiO₂ nanoparticle exposure. Increase in intracellular ROS level and reduction in GSH content were also observed in SiO₂ nanoparticle-exposed HEK293 cells. Increase in the amount of TBARS suggested an elevated level of lipid peroxidation. Flow cytometric analysis showed that SiO₂ nanoparticles can cause G2/M phase arrest and apoptotic sub-G1 population increase in a dose-dependent manner. In summary, exposure to SiO₂ nanoparticles resulted in a dose-dependent cytotoxicity in cultured HEK293 cells that was associated with increased oxidative stress.     

Effects of silver and gold nanoparticles of different sizes in human pulmonary fibroblasts

Abstract

Silver and gold nanoparticles (Ag–AuNPs) are currently some of the most manufactured nanomaterials. Accordingly, the hazards associated with human exposure to Ag–AuNPs should be investigated to facilitate the risk assessment process. In particular, because pulmonary exposure to Ag–AuNPs occurs during handling of these nanoparticles, it is necessary to evaluate the toxic response in pulmonary cells. The aim of this study was to evaluate the in vitro mechanisms of toxicity of different sizes of silver (4.7 and 42?nm) and gold nanoparticles (30, 50 and 90?nm) in human pulmonary fibroblasts (HPF). The toxicity was evaluated by observing cell viability and oxidative stress parameters. Data showed that AgNPs-induced cytotoxicity was size-dependent, whereas the AuNPs of the three sizes showed similar cytotoxicity. Silver nanoparticles of 4.7?nm were much more toxic than the large silver nanoparticles and the AuNPs. However, the pre-treatment with the antioxidant, N-acetyl-l-cysteine, protected HPF cells against treatment with Ag–AuNPs. The oxidative stress parameters revealed significant increase in reactive oxygen species levels, depletion of glutathione level and slight, but not statistically significant inactivation of superoxide dismutase, suggesting generation of oxidative stress. Hence, care has to be taken while processing and formulating the Ag–AuNPs till their final finished product.     

Contribution of oxidative stress to TiO2 nanoparticle-induced toxicity

With the rapid development of nanotechnology, titanium dioxide nanoparticles (TNPs) are widely used in many fields. People in such workplaces or researchers in laboratories are at a higher risk of being exposed to TNPs, so are the consumers. Moreover, increasing evidence revealed that the concentrations of TNPs are elevated in animal organs after systematic exposure and such accumulated TNPs could induce organ dysfunction. Although cellular responses such as oxidative stress, inflammatory response, apoptosis, autophagy, signaling pathways, and genotoxic effects contribute to the toxicity of TNPs, the interrelationship among them remains obscure. Given the pivotal role of oxidative stress, we summarized relevant articles covering the involvement of oxidative stress in TNPs’ toxicity and found that TNP-induced oxidative stress might play a central role in toxic mechanisms. However, available data are far from being conclusive and more investigations should be performed to further confirm whether the toxicity of TNPs might be attributed in part to the cascades of oxidative stress. Tackling this uncertain issue may help us to comprehensively understand the interrelationship among toxic cellular responses induced by TNPs and might shed some light on methods to alleviate toxicity of TNPs.     

金纳米粒子对CHO-K1细胞毒性的谷胱甘肽作用机制

目的探讨金纳米粒子(AuNP)对卵巢细胞CHO-K1的毒性作用及谷胱甘肽(GSH)的对抗作用。方法 AuNP 10～100μmol.L-1作用卵巢细胞CHO-K1 72 h,MTT比色法检测细胞存活。AuNP10μmo.lL-1,丁硫氨酸-亚砜亚胺(BSO)20μmo.lL-1及GSH 1 mmo.l L-1单独或联合作用细胞72 h,MTT比色法检测细胞增殖,倒置相差显微镜观察细胞形态,AnnexinⅤ-FITC和PI染色流式细胞仪检测细胞凋亡;AuNP 10μmo.l L-1,BSO 20μmo.l L-1及GSH 1 mmo.l L-1单独或联合作用细胞48 h,共聚焦显微镜检测细胞骨架微丝,JC-1染色流式细胞仪检测线粒体膜电位。结果 AuNP 10～100μmo.lL-1对正常的CHO-K1细胞存活无明显影响。与正常对照组相比,AuNP 10μmol.L-1和BSO 20μmol.L-1联合作用,可明显抑制CHO-K1细胞存活,抑制率为(80±2)%(P<0.01),胞体皱缩、变圆,细胞骨架微丝破坏;凋亡率为(66±6)%(P<0.01);细胞线粒体膜电位显著增加(P<0.01);加入外源性的GSH可逆转AuNP对因细胞GSH水平受抑而产生的细胞毒性。结论 AuNP对CHO-K1细胞损伤可能与GSH水平降低有关。     

Exposure to silver nanoparticles induces size- and dose-dependent oxidative stress and cytotoxicity in human colon carcinoma cells

The antimicrobial properties of silver nanoparticles (AgNPs) have made these particles one of the most frequently utilized nanomaterials in consumer products; therefore, a comprehensive understanding of their toxicity is necessary. In particular, information about the cellular uptake and size dependence of AgNPs is insufficient.In this study, we evaluated the size-dependent effects of AgNPs by treating the human LoVo cell line, an intestinal epithelium model, with spherical AgNPs of well-defined sizes (10, 20, 40, 60 and 100 nm). The cellular uptake was visualized by confocal laser scanning microscopy, and various cytotoxicity parameters were analyzed in a size- and dose-dependent manner. In addition, the cellular proteomic response to 20 and 100 nm AgNPs was investigated to increase the understanding of potential mechanisms of action. Our data indicated that cellular uptake and toxicity were regulated by size; smaller particles easily penetrated the cells, and 100 nm particles did not. It was hypothesized that this size-dependent effect resulted from the stimulation of a signaling cascade that generated ROS and inflammatory markers, leading to mitochondrial dysfunction and subsequently inducing apoptosis. By contrast, the cell proliferation, was independent of AgNPs particle size, indicating a differentially regulated, ROS-independent pathway.     

Cytotoxicity,oxidative stress,and inflammation in human Hep G2 liver epithelial cells following exposure to gold nanorods

The gold nanorods (GNRs) are great potentials in imaging, therapy, biosensing, and many other commercial applications. However, GNRs interactions with human cells and potential health risks remain not well known. The present investigation aimed to evaluate the in vitro toxicity of 10 and 25?nm GNRs (10–50?μg/mL) following exposure for 48?h in human Hep G2 liver epithelial cells using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH) leakage, glutathione (GSH) estimation, lipid peroxidation (TBARS), caspase-3 levels, and interleukin-8 (IL-8) release assays. Exposure of GNRs to cells results in decrease in cell viability and causes cell membrane damage through LDH leakage results in cytotoxicity. The IC₅₀ (concentration required to inhibit 50% of cells) values of 10?nm GNRs, 25?nm GNRs, and quartz (toxic control)-treated cells were found to be 19.9, 26.8, and 36.35?μg/mL, suggesting the higher cytotoxicity of GNRs. The GNRs exposure to liver cells found in depleted GSH levels, increased lipid peroxidation, and increased caspase-3 levels leads to induction of oxidative stress. In addition, enhanced levels of IL-8 were found, a sign of inflammation. The 10?nm GNRs have shown significant toxicity against all biochemical assays when compare to 25?nm GNRs and quartz-treated cells. Finally, the data indicate that the concentration size-dependent in vitro toxicity of GNRs toward liver Hep G2 cells. The toxicity of GNRs may be due to cell membrane damage, induction of oxidative stress, and inflammatory mediator release. Further investigations are necessitated to elucidate the in vivo toxicity of GNRs.     

Comparative cytotoxicity of nanosilver in human liver HepG2 and colon Caco2 cells in culture

The use of silver nanoparticles in food, food contact materials, dietary supplements and cosmetics has increased significantly owing to their antibacterial and antifungal properties. As a consequence, the need for validated rapid screening methods to assess their toxicity is necessary to ensure consumer safety. This study evaluated two widely used in vitro cell culture models, human liver HepG2 cells and human colon Caco2 cells, as tools for assessing the potential cytotoxicity of food‐ and cosmetic‐related nanoparticles. The two cell culture models were utilized to compare the potential cytotoxicity of 20‐nm silver. The average size of the silver nanoparticle determined by our transmission electron microscopy (TEM) analysis was 20.4 nm. The dynamic light scattering (DLS) analysis showed no large agglomeration of the silver nanoparticles. The concentration of the 20‐nm silver solution determined by our inductively coupled plasma–mass spectrometry (ICP‐MS) analysis was 0.962 mg ml^–1. Our ICP‐MS and TEM analysis demonstrated the uptake of 20‐nm silver by both HepG2 and Caco2 cells. Cytotoxicity, determined by the Alamar Blue reduction assay, was evaluated in the nanosilver concentration range of 0.1 to 20 µg ml^–1. Significant concentration‐dependent cytotoxicity of the nanosilver in HepG2 cells was observed in the concentration range of 1 to 20 µg ml^–1 and at a higher concentration range of 10 to 20 µg ml^–1 in Caco2 cells compared with the vehicle control. A concentration‐dependent decrease in dsDNA content was observed in both cell types exposed to nanosilver but not controls, suggesting an increase in DNA damage. The DNA damage was observed in the concentration range of 1 to 20 µg ml^–1. Nanosilver‐exposed HepG2 and Caco2 cells showed no cellular oxidative stress, determined by the dichlorofluorescein assay, compared with the vehicle control in the concentration range used in this study. A concentration‐dependent decrease in mitochondria membrane potential in both nanosilver exposed cell types suggested increased mitochondria injury compared with the vehicle control. The mitochondrial injury in HepG2 cells was significant in the concentration range of 1 to 20 µg ml^–1, but in Caco2 cells it was significant at a higher concentration range of 10 to 20 µg ml^–1. These results indicated that HepG2 cells were more sensitive to nanosilver exposure than Caco2 cells. It is generally believed that cellular oxidative stress induces cytotoxicity of nanoparticles. However, in this study we did not detect any nanosilver‐induced oxidative stress in either cell type at the concentration range used in this study. Our results suggest that cellular oxidative stress did not play a major role in the observed cytotoxicity of nanosilver in HepG2 and Caco2 cells and that a different mechanism of nanosilver‐induced mitochondrial injury leads to the cytotoxicity. The HepG2 and Caco2 cells used this study appear to be targets for silver nanoparticles. The results of this study suggest that the differences in the mechanisms of toxicity induced by nanosilver may be largely as a consequence of the type of cells used. This differential rather than universal response of different cell types exposed to nanoparticles may play an important role in the mechanism of their toxicity. In summary, the results of this study indicate that the widely used in vitro models, HepG2 and Caco2 cells in culture, are excellent systems for screening cytotoxicity of silver nanoparticles. These long established cell culture models and simple assays used in this study can provide useful toxicity and mechanistic information that can help to better inform safety assessments of food‐ and cosmetic‐related silver nanoparticles. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.     

药用纳米SiO2对人正常肺细胞的氧化损伤

目的：探讨药用纳米SiO2对人正常肺细胞MRC-5的生长抑制与氧化损伤作用。方法：纳米SiO2暴露于MRC-5细胞48h后,以MTT法测定其对细胞增殖的影响,HE染色观察细胞的形态学变化,并检测暴露后细胞内活性氧（ROS）和还原型谷胱甘肽（GSH）含量以及超氧化物歧化酶（SOD）活性的改变,分析纳米材料对MRC-5细胞的氧化损伤作用。结果：两种尺度（粒径21.6、48.6nm）纳米SiO2暴露浓度分别达到0.4mg/mL与1.0mg/mL以上时,细胞存活率随暴露剂量的增加而降低,IC50分别为0.8mg/mL和1.9mg/mL。细胞形态皱缩,核质凝聚。细胞内活性氧明显升高（P〈0.01）,GSH含量和SOD活性显著降低（P〈0.05）,且呈现明显的剂量效应关系。结论：较高浓度纳米SiO2直接暴露可抑制人正常肺细胞MRC-5的增殖,其机理与细胞的氧化损伤有关。     

Aluminium oxide nanoparticles induced morphological changes,cytotoxicity and oxidative stress in Chinook salmon (CHSE‐214) cells

Aluminium oxide nanoparticles (Al₂O₃ NPs) are increasingly used in diverse applications that has raised concern about their safety. Recent studies suggested that Al₂O₃ NPs induced oxidative stress may be the cause of toxicity in algae, Ceriodaphnia dubia, Caenorhabditis elegans and Danio rerio. However, there is paucity on the toxicity of Al₂O₃ NPs on fish cell lines. The current study was aimed to investigate Al₂O₃ NPs induced cytotoxicity, oxidative stress and morphological abnormality of Chinnok salmon cells (CHSE‐214). A dose‐dependent decline in cell viability was observed in CHSE‐214 cells exposed to Al₂O₃ NPs. Oxidative stress induced by Al₂O₃ NPs in CHSE‐214 cells has resulted in the significant reduction of superoxide dismutase, catalase and glutathione in a dose‐dependent manner. However, a significant increase in glutathione sulfo‐transferase and lipid peroxidation was observed in CHSE‐214 cells exposed to Al₂O₃ NPs in a dose‐dependent manner. Significant morphological changes in CHSE‐214 cells were observed when exposed to Al₂O₃ NPs at 6, 12 and 24 h. The cells started to detach and appear spherical at 6 h followed by loss of cellular contents resulting in the shrinking of the cells. At 24 h, the cells started to disintegrate and resulted in cell death. Our data demonstrate that Al₂O₃ NPs induce cytotoxicity and oxidative stress in a dose‐dependent manner in CHSE‐214 cells. Thus, our current work may serve as a base‐line study for future evaluation of toxicity studies using CHSE‐214 cells. Copyright © 2015 John Wiley & Sons, Ltd.     

Influence of the surface coating on the cytotoxicity,genotoxicity and uptake of gold nanoparticles in human HepG2 cells

The toxicological profile of gold nanoparticles (AuNPs) remains controversial. Significant efforts to develop surface coatings to improve biocompatibility have been carried out. In vivo biodistribution studies have shown that the liver is a target for AuNPs accumulation. Therefore, we investigated the effects induced by ~20 nm spherical AuNPs (0–200 μM Au) with two surface coatings, citrate (Cit) compared with 11‐mercaptoundecanoic acid (11‐MUA), in human liver HepG2 cells. Cytotoxicity was evaluated using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release assays after 24 to 72 h of incubation. DNA damage was assessed by the comet assay, 24 h after incubation with the capped AuNPs. Uptake and subcellular distribution of the tested AuNPs was evaluated by quantifying the gold intracellular content by graphite furnace atomic absorption spectrometry (GFAAS) and transmission electron microscopy (TEM), respectively. The obtained results indicate that both differently coated AuNPs did not induce significant cytotoxicity. An inverse concentration‐dependent increase in comet tail intensity and tail moment was observed in Cit‐AuNPs‐ but not in MUA‐AuNPs‐exposed cells. Both AuNPs were internalized in a concentration‐dependent manner. However, no differences were found in the extent of the internalization between the two types of NPs. Electron‐dense deposits of agglomerates of Cit‐ and MUA‐AuNPs were observed either inside endosomes or in the intercellular spaces. In spite of the absence of cytotoxicity, DNA damage was observed after exposure to the lower concentrations of Cit‐ but not to MUA‐AuNPs. Thus, our data supports the importance of the surface properties to increase the biocompatibility and safety of AuNPs. Copyright © 2013 John Wiley & Sons, Ltd.     

Methamidophos induces cytotoxicity and oxidative stress in human peripheral blood mononuclear cells

Previous studies have shown that organophosphate pesticide (OP) exposure is associated with oxidative stress. Methamidophos (MET) is an OP widely used in agriculture, which is regarded as a highly toxic pesticide and it is a potent inhibitor of acetylcholinesterase. The aim of this study was to evaluate whether MET can induce oxidative stress at low concentrations in primary cultures of human peripheral blood mononuclear cells (PBMCs). PBMCs from healthy individuals were exposed to MET (0–80 mg/L) for 0–72 h. We performed the MTT and neutral‐red assays to assess the cytotoxicity. As indicators of oxidative stress, the levels of reactive oxygen species (ROS) were assessed using flow cytometry, and the malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined. MET decreased the viability of PBMCs in a dose‐dependent manner. At concentrations of 3, 10, or 20 mg/L for 24 h, MET increased the ROS production significantly compared with the vehicle control. Similarly, MET increased the levels of MDA at the same concentrations that increased ROS (10 and 20 mg/L); however, no changes in GSH levels were observed. These results suggest that MET increased the generation of oxidative stress in PBMCs. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 147–155, 2017.     

Comparative cytotoxicity of dolomite nanoparticles in human larynx HEp2 and liver HepG2 cells

Dolomite is a natural mineral of great industrial and commercial importance. With the advent of nanotechnology, natural minerals including dolomite in the form of nanoparticles (NPs) are being utilized in various applications to improve the quality of products. However, safety or toxicity information of dolomite NPs is largely lacking. This study evaluated the cytotoxicity of dolomite NPs in two widely used in vitro cell culture models: human airway epithelial (HEp2) and human liver (HepG2) cells. Concentration‐dependent decreased cell viability and damaged cell membrane integrity revealed the cytotoxicity of dolomite NPs. We further observed that dolomite NPs induce oxidative stress in a concentration‐dependent manner, as indicated by depletion of glutathione and induction of reactive oxygen species (ROS) and lipid peroxidation. Quantitative real‐time PCR data demonstrated that the mRNA level of tumor suppressor gene p53 and apoptotic genes (bax, CASP3 and CASP9) were up‐regulated whereas the anti‐apoptotic gene bcl‐2 was down‐regulated in HEp2 and HepG2 cells exposed to dolomite NPs. Moreover, the activity of apoptotic enzymes (caspase‐3 and caspase‐9) was also higher in both kinds of cells treated with dolomite NPs. It is also worth mentioning that HEp2 cells seem to be marginally more susceptible to dolomite NPs exposure than HepG2 cells. Cytotoxicity induced by dolomite NPs was efficiently prevented by N‐acetyl cysteine treatment, which suggests that oxidative stress is primarily responsible for the cytotoxicity of dolomite NPs in both HEp2 and HepG2 cells. Toxicity mechanisms of dolomite NPs warrant further investigations at the in vivo level. Copyright © 2015 John Wiley & Sons, Ltd.     

同型半胱氨酸激活JNK信号通路诱导血管平滑肌细胞氧化应激的损伤研究

目的 观察同型半胱氨酸（Hcy）在A10血管平滑肌细胞株（vascular smooth muscle cells,VSMC）上对氧化应激的影响及其可能的分子机制。方法 在体外培养的A10细胞上,用3个不同浓度（5、30和100 μmol/L）的Hcy孵育细胞共48 h,随后破裂细胞,一方面使用试剂盒检测细胞裂解液中的活性氧（ROS）水平、H₂O₂含量、总抗氧化能力（T-AOC）,以评价其氧化应激情况。另一方面,用免疫印迹法检测磷酸化应激活化蛋白激酶（JNK）及总JNK的表达量。结果 Hcy可诱导ROS、H₂O₂的含量升高,而导致T-AOC的水平下降。而且,Hcy增加了磷酸化JNK的蛋白表达量（P<0.05）。结论 Hcy在VSMC上通过激活JNK信号通路诱导氧化应激。     

Low-dose methylmercury-induced oxidative stress, cytotoxicity, and tau-hyperphosphorylation in human neuroblastoma (SH-SY5Y) cells

Acute neurotoxic effects of high-dose methylmercury (MeHg) in humans have been well documented in the scientific literature. However, low-dose effects are less well described. This study was designed to evaluate the effects of low-dose MeHg (<100 nM) on human brain cells in a tissue culture model. Neuroblastoma (NB) cells (SH-SY5Y) were used in the cell culture model to study low-dose effects of MeHg on cell growth, cell survival, reactive oxygen species (ROS), and the phosphorylation of tau protein, as a measure of potential markers of cellular events associated with tauopathies. When cells were incubated in culture with MeHg (50 and 100 nM), there were significant decreases in cell viability as well as significant increase in ROS generation as determined by fluorescent dye analysis (H(2)DCFDA). Furthermore, a concomitant decrease in glutathione levels to 25% of control was observed at both 50 and 100 nM MeHg. In addition, the level of phosphorylated tau was significantly increased after treatment at both 50 and 100 nM MeHg, compared with controls. Pretreatment of NB cells with the antioxidant, N-acetylcysteine (1.25 mM) and the calpain inhibitor, MDL-28170 (10 μM), significantly attenuated the effects of MeHg (50 and 100 nM) on cell viability as well as on tau phosphorylation. These results indicate that low-dose MeHg toxicity may be related to an induction of tau phosphorylation through an oxidative stress-dependent mechanism and that blockade of this pathway may attenuate the toxic effects of MeHg.     

Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells

As the applications of industrial nanoparticles are being developed, the concerns on the environmental health are increasing. Cytotoxicities of titanium dioxide nanoparticles of different concentrations (5, 10, 20 and 40mug/ml) were evaluated in this study using a cultured human bronchial epithelial cell line, BEAS-2B. Exposure of the cultured cells to nanoparticles led to cell death, reactive oxygen species (ROS) increase, reduced glutathione (GSH) decrease, and the induction of oxidative stress-related genes such as heme oxygenase-1, thioredoxin reductase, glutathione-S-transferase, catalase, and a hypoxia inducible gene. The ROS increase by titanium dioxide nanoparticles triggered the activation of cytosolic caspase-3 and chromatin condensation, which means that titanium dioxide nanoparticles exert cytotoxicity by an apoptotic process. Furthermore, the expressions of inflammation-related genes such as interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), TNF-a, and C-X-C motif ligand 2 (CXCL2) were also elevated. The induction of IL-8 by titanium dioxide nanoparticles was inhibited by the pre-treatment with SB203580 and PD98059, which means that the IL-8 was induced through p38 mitogen-acitvated protein kinase (MAPK) pathway and/or extracellular signal (ERK) pathway. Uptake of the nanoparticles into the cultured cells was observed and titanium dioxide nanoparticles seemed to penetrate into the cytoplasm and locate in the peri-region of the nucleus as aggregated particles, which may induce direct interactions between the particles and cellular molecules, to cause adverse biological responses.     

Investigation of flurbiprofen genotoxicity and cytotoxicity in rat bone marrow cells

This study was performed to investigate cytogenetic effects of NSAID flurbiprofen which was used as active ingredient in some analgesic, antipyretic and anti-inflammatory drugs. Genotoxic effect of flurbiprofen was investigated using in vivo chromosome aberration (CA) test and random amplified polymorphic DNA–polymerase chain reaction (RAPD-PCR) test. Also, oxidative stress potential of flurbiprofen was determined by measuring total oxidant and antioxidant level which occurred with flurbiprofen treatment in rat peripheral blood. For these purposes, rats were treated with three concentrations of flurbiprofen (29.25, 58.50 and 117?mg/kg, body weight) in single dose at two different treatment periods (12 and 24?h). According to the results, flurbiprofen did not affect chromosome aberrations in rat bone marrow cells with CA test. In RAPD-PCR test, polymorphic bands were unaffected. Also, test substance did not change total oxidant and antioxidant status (except for 58.50 and 117?mg/kg, 12?h) and therefore it did not lead to significant increase on oxidative stress (again except 58.50 and 117?mg/kg, 12?h). However, flurbiprofen reduced to mitotic indexes and these reductions were dose-dependent for 12?h treatment. In summary, flurbiprofen did not show significant genotoxic effect. But it caused cytotoxicity in rat bone marrow cells.     

Evaluation of cytotoxic,oxidative stress,proinflammatory and genotoxic effect of silver nanoparticles in human lung epithelial cells

Silver nanoparticles are increasingly used in various products, due to their antibacterial properties. Despite its wide spread use, only little information on possible adverse health effects exists. Therefore, the aim of this study was to assess the toxic potential of silver nanoparticles (<100 nm) in human lung epithelial (A549) cells and the underlying mechanism of its cellular toxicity. Silver nanoparticles induced dose and time‐dependent cytotoxicity in A549 cells demonstrated by MTT and LDH assays. Silver nanoparticles were also found to induce oxidative stress in dose and time‐dependent manner indicated by depletion of GSH and induction of ROS, LPO, SOD, and catalase. Further, the activities of caspases and the level of proinflammatory cytokines, namely interleukin‐1β (IL‐1β) and interleukin‐6 (IL‐6) were significantly higher in treated cells. DNA damage, as measured by single cell gel electrophoresis, was also dose and time‐dependent signicants in A549 cells. This study investigating the effects of silver nanoparticles in human lung epithelial cells has provided valuable insights into the mechanism of potential toxicity induced by silver nanoparticles and warrants more careful assessment of silver nanoparticles before their industrial applications. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 149–160, 2015.     

Mitochondrial dysfunction in titanium dioxide nanoparticle-induced neurotoxicity

Abstract

Nanotechnology has emerged as a field of scientific innovation which has opened up a plethora of concerns for the potential impact on human and environment. Various toxicological studies have confirmed that nanoparticles (NPs) can be potentially hazardous because of their unique small size and physico-chemical properties. With the wide applications of titanium dioxide nanoparticles (TNPs) in day-to-day life in form of cosmetics, paints, sterilization and so on, there is growing concern regarding the deleterious effects of TNPs on central nervous system. Mitochondria is an important origin for generation of energy as well as free radicals and these free radicals can lead to mitochondrial damage and finally lead to apoptosis. The objective of our study was to elucidate the potential neurotoxic effect of TNPs in anatase form. Oxidative stress was determined by measuring lipid peroxidation and protein carbonyl content which was found to be significantly increased. Reduced glutathione content and major glutathione metabolizing enzymes were also modulated signifying the role of glutathione redox cycle in the pathophysiology of TNPs. Mitochondrial complexes were also modulated from the exposure to TNPs. The present study indicates that nanosize TNPs may pose a health risk to mitochondrial brain with the generation of reactive oxygen species, and thus NPs should be carefully used.