Cytotoxicity and genotoxicity of methomyl, carbaryl, metalaxyl, and pendimethalin in human umbilical vein endothelial cells.

Pesticides have adverse effects on the cellular functionality, which may trigger myriad of health consequences. However, pesticides-mediated toxicity in the endothelial cells (ECs) is still elusive. Hence, in this study, we have used human umbilical vein endothelial cells (HUVECs) as a model to quantify the cytotoxicity and genotoxicity of four pesticides (methomyl, carbaryl, metalaxyl, and pendimethalin). In the MTT assay, HUVECs exposed to methomyl, carbaryl, metalaxyl, and pendimethalin demonstrated significant proliferation inhibition only at higher concentrations (500 and 1000 µM). Likewise, neutral red uptake (NRU) assay also showed proliferation inhibition of HUVECs at 500 and 1000 µM by the four pesticides, confirming lysosomal fragility. HUVECs exposed to the four pesticides significantly increased the level of intracellular reactive oxygen species (ROS). Comet assay and flow cytometric data exhibited DNA damage and apoptotic cell death in HUVECs after 24 h of exposure with methomyl, metalaxyl, carbaryl, and pendimethalin. This is a first study on HUVECs signifying the cytotoxic-genotoxic and apoptotic potential of carbamate insecticides (methomyl and carbaryl), fungicide (metalaxyl), and herbicide (pendimethalin). Overall, these pesticides may affect ECs functions and angiogenesis; nonetheless, mechanistic studies are warranted from the perspective of vascular biology using in vivo test models.

Interaction of Copper-Based Nanoparticles to Soil, Terrestrial, and Aquatic Systems: Critical Review of the State of the Science and Future Perspectives.

In the past two decades, increased production and usage of metallic nanoparticles (NPs) have inevitably increased their discharge into the different compartments of the environment, which ultimately paved the way for their uptake and accumulation in various trophic levels of the food chain. Due to these issues, several questions have been raised on the usage of NPs in everyday life and have become a matter of public health concern. Among the metallic NPs, Cu-based NPs have gained popularity due to their cost-effectiveness and multifarious promising uses. Several studies in the past represented the phytotoxicity of Cu-based NPs on plants. However, comprehensive knowledge is still lacking. Additionally, the impact of Cu-based NPs on soil organisms such as agriculturally important microbes, fungi, mycorrhiza, nematode, and earthworms is poorly studied. This review article critically analyses the literature data to achieve a more comprehensive knowledge on the toxicological profile of Cu-based NPs and increase our understanding of the effects of Cu-based NPs on aquatic and terrestrial plants as well as on soil microbial communities. The underlying mechanism of biotransformation of Cu-based NPs and the process of their penetration into plants have also been discussed herein. Overall, this review could provide valuable information to design rules and regulations for the safe disposal of Cu-based NPs into a sustainable environment.

ARSACS as a Worldwide Disease: Novel SACS Mutations Identified in a Consanguineous Family from the Remote Tribal Jammu and Kashmir Region in India.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder characterized by the triad of early-onset cerebellar ataxia, peripheral sensorimotor neuropathy, and lower limb spasticity. Here, we present a 28-year-old male patient with symptoms of ARSACS and mild intellectual disability from a consanguineous family of tribal J&K, India. Whole exome sequencing unraveled a novel homozygous frameshift SACS mutation (Cys2869ValfsTer15) in the patient. In addition to the well-established ARSACS imaging features, MRI revealed T2 hyperintense rim around the thalami ("bithalamic stripes") demonstrating that this feature might serve as an additional supportive diagnostic imaging marker for ARSACS. Moreover, retinal nerve fiber layer thickening which has recently been proposed as a diagnostic biomarker for ARSACS was present on routine optic coherence tomography (OCT) also in this patient, indicating that it might indeed present a relatively universal diagnostic biomarker for ARSACS. In sum, our findings extend the geographical distribution of ARSACS to even very remote tribal regions in Asia (such as the Rajouri region of J&K, India) and extend the mutational and imaging spectrum of ARSACS. They provide further support that brain imaging and OCT markers might serve as diagnostic biomarkers for ARSACS in patients with novel SACS mutations, applicable even in remote regions of the world to identify and confirm ARSACS disease.

Effective Inhibition of Phytopathogenic Microbes by Eco-Friendly Leaf Extract Mediated Silver Nanoparticles (AgNPs).

ABSTRACT: This study was aimed at producing the eco-friendly, safe, and inexpensive silver (Ag) nanoparticles (NPs) and assessing its antimicrobial activity. Fungal pathogens isolated from diseased leaves and fruits of brinjal and bacterial pathogen obtained from a culture collection were used in this study. Green synthesis of AgNPs was performed and optimized using Azadirachta indica leaf extract. The newly synthesized AgNPs (λmax = 437 nm) showed isotropism in size (crystal size/diameter: 21/29 ± 5 nm) and morphology under transmission and scanning electron microscopy and energy dispersive X-ray analysis. The fourier transform infrared spectroscopy data suggested the role of various aliphatic/aromatic moieties and proteins in AgNPs stabilization. The AgNPs reduced the growth of Penicillium sp. maximally by 92% after 6 days. The sensitivity of test fungi towards AgNPs followed the order: Penicillium sp. (92%) > Fusarium sp. (89%) > Aspergillus sp. (69%). Exposure of Ralstonia solanacearum to AgNPs (MIC/MBC 200/400 µg ml-1) displayed damaged cellular envelopes, bulging of cells, and pit formation. The nucleic acid discharge showed a progressive increase from 8 to 34% (r2 = 0.97). The cellular metabolic activity and surface adhering ability of R. solanacearum were completely lost at 400 µgAgNPs ml-1. Results suggested that the AgNPs synthesized in this study had enough anti-pathogenic potential and could inexpensively and safely be used as a promising alternative to agrochemicals. Moreover, the findings observed in this study is likely to serve as an important indicator for the development of effective nano-control agents which in effect would help to manage some deadly phyto-pathogens capable of causing heavy losses to agricultural production systems. GRAPHICAL ABSTRACT: Effective inhibition of phytopathogenic microbes by eco-friendly neem leaf extract mediated silver nanoparticles (AgNPs).

Pendimethalin induces oxidative stress, DNA damage, and mitochondrial dysfunction to trigger apoptosis in human lymphocytes and rat bone-marrow cells.

Pendimethalin (PM) is a dinitroaniline herbicide extensively applied against the annual grasses and broad-leaved weeds. There is no report available on PM-induced low-dose genotoxicity in human primary cells and in vivo test models. Such data gap has prompted us to evaluate the genotoxic potential of PM in human lymphocytes and rats. PM selectively binds in the minor groove of DNA by forming covalent bonds with G and C nitrogenous bases, as well as with the ribose sugar. PM induces micronucleus formation (MN) in human lymphocytes, indicating its clastogenic potential. Comet assay data showed 35.6-fold greater DNA damage in PM (200 µM)-treated human lymphocytes. Rat bone-marrow cells, at the highest dose of 50 mg/kg b w/day of PM also exhibited 10.5-fold greater DNA damage. PM at 200 µM and 50 mg/kg b w/day induces 193.4 and 229% higher reactive oxygen species generation in human lymphocytes and rat bone-marrow cells. PM-treated human lymphocytes and rat bone-marrow cells both showed dysfunction of mitochondrial membrane potential (ΔΨ m). PM exposure results in the appearance of 72.2 and 35.2% sub-G1 apoptotic peaks in human lymphocytes and rat bone-marrow cells when treated with 200 µM and 50 mg/kg b w/day of PM. Rats exposed to PM also showed imbalance in antioxidant enzymes and histological pathology. Overall, our data demonstrated the genotoxic and apoptotic potentials of PM in human and animal test models.

Bio-inspired nanomaterials in agriculture and food: Current status, foreseen applications and challenges.

Nanotechnology is a potential area that revolutionizes almost every sector of life and is predicted to become a major economic force in the near future. Recently, nanomaterials have received great attention for their properties at nanoscale regime and their applications in many areas primarily, agriculture and food sectors. The Nanomaterials are dispersed or solid particles, with a size range of 1-100 nm. In recent times, there has been an increased research work in this area to synthesize nanomaterials using various approaches. The use of natural biomolecules using 'green' approach play key role in the synthesis of nanomaterials having different shapes and sizes. Further this 'green synthesis' approach not only minimize the cost but also limit the need of hazardous chemicals and stimulates synthesis of greener, safe and environmentally friendly nanoparticles. The present review focus on studies based on the biosynthesis of nanoparticles using biomolecules such as plants, bacteria, fungi, etc. The text summarizes the recent work done globally by renowned researchers in area of biosynthesis of nanomaterials. It also discusses the potential applications of biologically mediated nanomaterials in the areas of agriculture and food and a critical evaluation of challenges within this field.

Toxicogenomics: A New Paradigm for Nanotoxicity Evaluation.

The wider applications of nanoparticles (NPs) has evoked a world-wide concern due to their possible risk of toxicity in humans and other organisms. Aggregation and accumulation of NPs into cell leads to their interaction with biological macromolecules including proteins, nucleic acids and cellular organelles, which eventually induce toxicological effects. Application of toxicogenomics to investigate molecular pathway-based toxicological consequences has opened new vistas in nanotoxicology research. Indeed, genomic approaches appeared as a new paradigm in terms of providing information at molecular levels and have been proven to be as a powerful tool for identification and quantification of global shifts in gene expression. Toxicological responses of NPs have been discussed in this chapter with the aim to provide a clear understanding of the molecular mechanism of NPs induced toxicity both in in vivo and in vitro test models.

Nickel Oxide Nanoparticles Induced Transcriptomic Alterations in HEPG2 Cells.

Nickel oxide nanoparticles (NiO-NPs) are increasingly used and concerns have been raised on its toxicity. Although a few studies have reported the toxicity of NiO-NPs, a comprehensive understanding of NiO-NPs toxicity in human cells is still lagging. In this study, we integrated transcriptomic approach and genotoxic evidence to depict the mechanism of NiO-NPs toxicity in human hepatocellular carcinoma (HepG2) cells. DNA damage analysis was done using comet assay, which showed 26-fold greater tail moment in HepG2 cells at the highest concentration of 100 µg/ml. Flow cytometric analysis showed concentration dependent enhancement in intracellular reactive oxygen species (ROS). Real-time PCR analysis of apoptotic (p53, bax, bcl2) and oxidative stress (SOD1) genes showed transcriptional upregulation. Transcriptome analysis using qPCR array showed over expression of mRNA transcripts related to six different cellular pathways. Our data unequivocally suggests that NiO-NPs induces oxidative stress, DNA damage, apoptosis and transcriptome alterations in HepG2 cells.

Inhibition of growth and biofilm formation of clinical bacterial isolates by NiO nanoparticles synthesized from Eucalyptus globulus plants.

Nanotechnology based therapeutics has emerged as a promising approach for augmenting the activity of existing antimicrobials due to the unique physical and chemical properties of nanoparticles (NPs). Nickel oxide nanoparticles (NiO-NPs) have been suggested as prospective antibacterial and antitumor agent. In this study, NiO-NPs have been synthesized by a green approach using Eucalyptus globulus leaf extract and assessed for their bactericidal activity. The morphology and purity of synthesized NiO-NPs determined through various spectroscopic techniques like UV-Visible, FT-IR, XRD, EDX and electron microscopy differed considerably. The synthesized NiO-NPs were pleomorphic varying in size between 10 and 20 nm. The XRD analysis revealed the average size of NiO-NPs as 19 nm. The UV-Vis spectroscopic data showed a strong SPR of NiO-NPs with a characteristic spectral peak at 396 nm. The FTIR data revealed various functional moieties like C=C, C-N, C-H and O-H which elucidate the role of leaf biomolecules in capping and dispersal of NiO-NPs. The bioactivity assay revealed the antibacterial and anti-biofilm activity of NiO-NPs against ESßL (+) E. coli, P. aeruginosa, methicillin sensitive and resistant S. aureus. Growth inhibition assay demonstrated time and NiO-NPs concentration dependent decrease in the viability of treated cells. NiO-NPs induced biofilm inhibition was revealed by a sharp increase in characteristic red fluorescence of PI, while SEM images of NiO-NPs treated cells were irregular shrink and distorted with obvious depressions/indentations. The results suggested significant antibacterial and antibiofilm activity of NiO-NPs which may play an important role in the management of infectious diseases affecting human health.

Zinc oxide and titanium dioxide nanoparticles induce oxidative stress, inhibit growth, and attenuate biofilm formation activity of Streptococcus mitis.

Streptococcus mitis from the oral cavity causes endocarditis and other systemic infections. Rising resistance against traditional antibiotics amongst oral bacteria further aggravates the problem. Therefore, antimicrobial and antibiofilm activities of zinc oxide and titanium dioxide nanoparticles (NPs) synthesized and characterized during this study against S. mitis ATCC 6249 and Ora-20 were evaluated in search of alternative antimicrobial agents. ZnO and TiO2-NPs exhibited an average size of 35 and 13 nm, respectively. The IC50 values of ZnO and TiO2-NPs against S. mitis ATCC 6249 were 37 and 77 µg ml(-1), respectively, while the IC50 values against S. mitis Ora-20 isolate were 31 and 53 µg ml(-1), respectively. Live and dead staining, biofilm formation on the surface of polystyrene plates, and extracellular polysaccharide production show the same pattern. Exposure to these nanoparticles also shows an increase (26-83 %) in super oxide dismutase (SOD) activity. Three genes, namely bapA1, sodA, and gtfB like genes from these bacteria were identified and sequenced for quantitative real-time PCR analysis. An increase in sodA gene (1.4- to 2.4-folds) levels and a decrease in gtfB gene (0.5- to 0.9-folds) levels in both bacteria following exposure to ZnO and TiO2-NPs were observed. Results presented in this study verify that ZnO-NPs and TiO2-NPs can control the growth and biofilm formation activities of these strains at very low concentration and hence can be used as alternative antimicrobial agents for oral hygiene.

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 (ΔΨm) 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.

Differential cytotoxicity of copper ferrite nanoparticles in different human cells.

Copper ferrite nanoparticles (NPs) have the potential to be applied in biomedical fields such as cell labeling and hyperthermia. However, there is a lack of information concerning the toxicity of copper ferrite NPs. We explored the cytotoxic potential of copper ferrite NPs in human lung (A549) and liver (HepG2) cells. Copper ferrite NPs were crystalline and almost spherically shaped with an average diameter of 35 nm. Copper ferrite NPs induced dose-dependent cytotoxicity in both types of cells, evident by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide and neutral red uptake assays. However, we observed a quite different susceptibility in the two kinds of cells regarding toxicity of copper ferrite NPs. Particularly, A549 cells showed higher susceptibility against copper ferrite NP exposure than those of HepG2 cells. Loss of mitochondrial membrane potential due to copper ferrite NP exposure was observed. The mRNA level as well as activity of caspase-3 enzyme was higher in cells exposed to copper ferrite NPs. Cellular redox status was disturbed as indicated by induction of reactive oxygen species (oxidant) generation and depletion of the glutathione (antioxidant) level. Moreover, cytotoxicity induced by copper ferrite NPs was efficiently prevented by N-acetylcysteine treatment, which suggests that reactive oxygen species generation might be one of the possible mechanisms of cytotoxicity caused by copper ferrite NPs. To the best of our knowledge, this is the first report showing the cytotoxic potential of copper ferrite NPs in human cells. This study warrants further investigation to explore the mechanisms of differential toxicity of copper ferrite NPs in different types of cells. Copyright © 2016 John Wiley & Sons, Ltd.

Verbesina encelioides: cytotoxicity, cell cycle arrest, and oxidative DNA damage in human liver cancer (HepG2) cell line.

BACKGROUND: Cancer is a major health problem and exploiting natural products have been one of the most successful methods to combat this disease. Verbesina encelioides is a notorious weed with various pharmacological properties. The aim of the present investigation was to screen the anticancer potential of V. encelioides extract against human lung cancer (A-549), breast cancer (MCF-7), and liver cancer (HepG2) cell lines. METHODS: A-549, MCF-7, and HepG2 cells were exposed to various concentrations of (10-1000 µg/ml) of V. encelioides for 24 h. Further, cytotoxic concentrations (250, 500, and 1000 µg/ml) of V. encelioides induced oxidative stress (GSH and LPO), reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), cell cycle arrest, and DNA damage in HepG2 cells were studied. RESULTS: The exposure of cells to 10-1000 µg/ml of extract for 24 h, revealed the concentrations 250-1000 µg/ml was cytotoxic against MCF-7 and HepG2 cells, but not against A-549 cells. Moreover, the extract showed higher decrease in the cell viability against HepG2 cells than MCF-7 cells. Therefore, HepG2 cells were selected for further studies viz. oxidative stress (GSH and LPO), reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), cell cycle arrest, and DNA damage. The results revealed differential anticancer activity of V. encelioides against A-549, MCF-7 and HepG2 cells. A significant induction of oxidative stress, ROS generation, and MMP levels was observed in HepG2 cells. The cell cycle analysis and comet assay showed that V. encelioides significantly induced G2/M arrests and DNA damage. CONCLUSION: These results indicate that V. encelioides possess substantial cytotoxic potential and may warrant further investigation to develop potential anticancer agent.

In-Vitro dual inhibition of protein glycation, and oxidation by some Arabian plants.

BACKGROUND: Diabetes mellitus is a metabolic disorder of epidemic proportion, projected to become the major cause of morbidity and mortality in the world in future. Despite extensive research in understanding this disease at molecular level, and the discovery of new drugs, diabetes and its complications remain largely untreated. Many of the late diabetic complications are associated with the glycation of proteins in the body. Natural flora has long been a rich source for therapeutic agents, especially against diabetes. The present study deals with the anti-glycation properties of some medicinally important plants of Arabian region. METHODS: Twenty-six medicinal plants, commonly found in different regions of Arabian Peninsula, were evaluated for their protein anti-glycation activity by using BSA-MG glycation assay in-vitro. The extracts were incubated with BSA and MG at 37 °C for 9 days, each sample was then examined for the presence of fluorescence (λex 330 nm, and λem 420 nm), which represent the extent of protein glycation. Antioxidant activity was evaluated by using 1,1-diphenyl- 2-picrylhydrazyl (DPPH), iron chelation, and superoxide radical scavenging asaays. RESULTS: The data revealed that out of 26 medicinal plants, five plants viz. Sida cordifolia, Plumbago zeylanica, Tribulus terrestris, Glycyrrhiza glabra, and Rosa indica were active against the in-vitro protein glycation with IC50 values between 0.408- 1.690 mg/mL. Among the active plants, Glycyrrhiza glabra L. was found to be the most potent (IC50 = 0.408 ± 0.027 mg/mL), followed by Rosa indica (IC50 = 0.596 ± 0.0179 mg/mL), and Sida cordifolia L. (IC50 = 0.63 ± 0.009 mg/mL). The antioxidant potential of these plant extracts were also determined by using DPPH (2,2-diphenyl-1-picrylhydrazyl), iron chelation, and superoxide anion radical scavenging assays. Among five plants, Sida cordifolia exhibited a potent anti-oxidant activity in both DPPH and superoxide anion radical scavenging assays (IC50 = 0.005 ± 0.0004, and 0.078 ± 0.002 mg/mL, respectively), followed by Rosa indica (IC50 = 0.023 ± 0.0005 and 0.141 ± 0.003 mg/mL, respectively). CONCLUSIONS: Protein glycation in hyperglycemic conditions involve oxidative changes. Therefore dual inhibition of protein glycation and oxidation are desirable properties in any test substance investigated for therapeutic purposes.

Protective effect of Lepidium sativum seed extract against hydrogen peroxide-induced cytotoxicity and oxidative stress in human liver cells (HepG2).

CONTEXT: Garden cress [Lepidium sativum (Brassicaceae)] has been widely used to treat a number of ailments in traditional medicine. The pharmacological and preventive potential of Lepidium sativum, such as anti-inflammatory, antipyretic, antihypertensive, anti-ashthamatic, anticancer, and anti-oxidant, are well known. OBJECTIVE: The present investigation was designed to study the protective effects of chloroform extract of Lepidium sativum seed (LSE) against oxidative stress and cytotoxicity induced by hydrogen peroxide (H2O2) in human liver cells (HepG2). MATERIALS AND METHODS: Cytotoxicity of LSE and H2O2 was identified by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), neutral red uptake (NRU) assays, and morphological changes in HepG2. The cells were pre-exposed to biologically safe concentrations (5-25 µg/ml) of LSE for 24 h, and then cytotoxic (0.25 mM) concentration of H2O2 was added. After 24 h of the exposures, cell viability by MTT, NRU assays, and morphological changes in HepG2 were evaluated. Further, protective effects of LSE on reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), lipid peroxidation (LPO), and reduced glutathione (GSH) levels induced by H2O2 were studied. RESULTS: Pre-exposure of LSE significantly attenuated the loss of cell viability up to 48% at 25 µg/ml concentration against H2O2 (LD50 value = 2.5 mM). Results also showed that LSE at 25 µg/ml concentration significantly inhibited the induction of ROS generation (45%) and LPO (56%), and increases the MMP (55%) and GSH levels (46%). DISCUSSION AND CONCLUSION: The study suggests the cytoprotective effects of LSE against H2O2-induced toxicity in HepG2. The results also demonstrate the anti-oxidative nature of LSE.

Genotoxicity of ferric oxide nanoparticles in Raphanus sativus: Deciphering the role of signaling factors, oxidative stress and cell death.

We have studied the genotoxic and apoptotic potential of ferric oxide nanoparticles (Fe2O3-NPs) in Raphanus sativus (radish). Fe2O3-NPs retarded the root length and seed germination in radish. Ultrathin sections of treated roots showed subcellular localization of Fe2O3-NPs, along with the appearance of damaged mitochondria and excessive vacuolization. Flow cytometric analysis of Fe2O3-NPs (1.0mg/mL) treated groups exhibited 219.5%, 161%, 120.4% and 161.4% increase in intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), nitric oxide (NO) and Ca(2+) influx in radish protoplasts. A concentration dependent increase in the antioxidative enzymes glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (LPO) has been recorded. Comet assay showed a concentration dependent increase in deoxyribonucleic acid (DNA) strand breaks in Fe2O3-NPs treated groups. Cell cycle analysis revealed 88.4% of cells in sub-G1 apoptotic phase, suggesting cell death in Fe2O3-NPs (2.0mg/mL) treated group. Taking together, the genotoxicity induced by Fe2O3-NPs highlights the importance of environmental risk associated with improper disposal of nanoparticles (NPs) and radish can serve as a good indicator for measuring the phytotoxicity of NPs grown in NP-polluted environment.

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.

Concentration-dependent induction of reactive oxygen species, cell cycle arrest and apoptosis in human liver cells after nickel nanoparticles exposure.

Due to advent of nanotechnology, nickel nanoparticles (Ni NPs) are increasingly recognized for their utility in various applications including catalysts, sensors and electronics. However, the environmental and human health effects of Ni NPs have not been fully investigated. In this study, we examined toxic effects of Ni NPs in human liver (HepG2) cells. Ni NPs were prepared and characterized by X-ray diffraction, transmission electron microscopy and dynamic light scattering. We observed that Ni NPs (size, ∼28 nm; concentration range, 25-100 µg/mL) induced cytotoxicity in HepG2 cells and degree of induction was concentration-dependent. Ni NPs were also found to induce oxidative stress in dose-dependent manner evident by induction of reactive oxygen species and depletion of glutathione. Cell cycle analysis of cells treated with Ni NPs exhibited significant increase of apoptotic cell population in subG1 phase. Ni NPs also induced caspase-3 enzyme activity and apoptotic DNA fragmentation. Upregulation of cell cycle checkpoint gene p53 and bax/bcl-2 ratio with a concomitant loss in mitochondrial membrane potential suggested that Ni NPs induced apoptosis in HepG2 cells was mediated through mitochondrial pathway. This study warrants that applications of Ni NPs should be carefully assessed as to their toxicity to human health.

Zinc oxide quantum dots: a potential candidate to detain liver cancer cells.

The term cancer is used for diseases in which abnormal cells proliferate without control and are able to attack with other tissues. Over various types of cancers, liver cancer is the most hurtful disease, which affects the whole body system. The aim of the present study was to investigate the efficiency against cancer cells of HepG2 cells, with quantum dots of ZnO. The cytotoxic effects were analyzed with MTT assays in range of 1-100 µg/ml. The cells were exposed to ZnO-QDs and it exhibit significant reduction, which starts from concentration 5 µg/ml (4 %; p < 0.05). The assay was justified with quantitative RT-PCR and it demonstrates, exposure of ZnO-QDs on HepG2 cells. The level of mRNA expressions was significantly up-regulated (Bax, P53, and Caspase-3), whereas the anti-apoptotic gene (Bcl-2) was down-regulated. The QDs (5 ± 2 nm) were prepared via soft chemical solution process and analyzed using FESEM, TEM and HR-TEM.

Hepatoprotective potential of Lavandula coronopifolia extracts against ethanol induced oxidative stress-mediated cytotoxicity in HepG2 cells.

The present investigations were carried out to study the protective potential of four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM), ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known hepatotoxin in human hapatocellular carcinoma (HepG2) cells. Cells were pretreated with LCR, LCM, LCE, and LCL extracts (10-50 µg/ml) of L. coronopifolia for 24 h and then ethanol was added and incubated further for 24 h. After the exposure, cell viability using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red uptake assays and morphological changes in HepG2 cells were studied. Pretreatment with various extracts of L. coronpifolia was found to be significantly effective in countering the cytotoxic responses of ethanol. Antioxidant properties of these L. coronopifolia extracts against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and glutathione (GSH) levels induced by ethanol were investigated. Results show that pretreatment with these extracts for 24 h significantly inhibited ROS generation and LPO induced and increased the GSH levels reduced by ethanol. The data from the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia showed hepatoprotective activity against ethanol-induced damage in HepG2 cells. However, a comparative study revealed that the LCE extract was found to be the most effective and LCL the least effective. The hepatoprotective effects observed in the study could be associated with the antioxidant properties of these extracts of L. coronopifolia.