Zinc oxide nanoparticles induced oxidative stress in mouse bone marrow mesenchymal stem cells.

Engineered nanoparticles are developed for various applications in industrial, electrical, agricultural, pharmaceutical and medical fields due to their unique properties. Nanoparticles such as TiO(2) and ZnO are widely used in cosmetics for UV protection. The toxicological investigations of ZnO NPs are highly recommended because of the increasing use in various industrial and consumer products. The toxic potential of ZnO NPs was assumed to be caused by the release of free Zn+ ions in the medium. Many of the in vivo studies suggest the toxic nature of ZnO NPs, the in vitro studies are certainly important to elucidate the mechanism of toxicity. This study examined the toxicity of ZnO NPs with the average size of 6-8 nm on the isolated mice bone marrow mesenchymal stem cells. The study focuses on the cytotoxicity and oxidative stress-mediated cellular responses upon exposure to ZnO NPs. The results indicated that the exposure to ZnO NPs significantly affects cellular viability in a dose-dependent manner. Formation of reactive oxygen species (ROS) was found to be the mechanism of cellular toxicity. The release of Zn(+) ions from the nanoparticles, due to the instability of ZnO NPs in the acidic compartment of lysosomes, also increases the ROS generation. In addition to increased ROS production, damage of lysosomal membrane and the activation of executioner caspase-3 and caspase-7 were observed, which eventually ends in apoptosis.

Tobacco use and exposure to second-hand smoke among high school students in Ernakulum district, Kerala: A cross-sectional study.

Objectives: Tobacco use and exposure to second-hand smoke (SHS) in the home setting are major health hazards for adolescents. The objectives of this study were to estimate tobacco use and exposure to SHS among high school students in Ernakulam district of Kerala, India, and to investigate associated factors. Study design: Cross-sectional study. Methods: A school-based cross-sectional study was carried out in 25 randomly selected high schools from 210 schools in the Ernakulam educational district of Kerala, India. The minimum calculated sample size for ever-use of tobacco and SHS exposure was determined to be 2500, with 95% confidence interval (CI) and 10% relative precision. Data were collected using a semi-structured, pre-tested questionnaire from 2585 high school students. Data analyses were performed using SPSS version 20. Results: The ever-use of tobacco was reported to be 3.9% (95% CI 3.16 to 4.54) and the mean age of the participants was 13.97 ± 0.77 years. One-fifth of participants had tried a tobacco product before the age of 10 years. SHS exposure at home was reported by one in every 5 respondents (20.3%). Male gender (adjusted odds ratio [aOR] 8.79; 95% CI 3.16, 24.53), presence of a family member who smokes within the home (aOR 4.28; 95% CI 2.58, 7.12), lack of awareness about the harmful effects of SHS exposure (aOR 2.47; 95% CI 1.41, 5.18) and having seen an advertisement or promotion at point of sale (aOR 2.16; 95% CI 1.29, 3.60) were found to be independent predictors for tobacco use.Participants with respiratory infections were three times more likely to have experienced SHS exposure at home (aOR 2.87; 95% CI 2.21, 3.74), there was an 86% protective effect of SHS exposure for participants with a father in a professional occupation compared with unskilled profession (aOR 0.14; 95% CI 0.02, 0.67; p < 0.15) and participants with ever-use of tobacco were two times more likely to have experienced SHS exposure at home (aOR 1.63; 95% CI 3.13, 8.98). Conclusions: SHS exposure in the home environment continues to be high. Urgent innovative measures are necessary for the implementation of tobacco smoke-free homes and to reduce tobacco use in this vulnerable population. Further studies are necessary to determine ways to reduce smoking within homes and to increase population awareness.

Comprehensive Application of Graphene: Emphasis on Biomedical Concerns.

Graphene, sp2 hybridized carbon framework of one atom thickness, is reputed as the strongest material to date. It has marked its impact in manifold applications including electronics, sensors, composites, and catalysis. Current state-of-the-art graphene research revolves around its biomedical applications. The two-dimensional (2D) planar structure of graphene provides a large surface area for loading drugs/biomolecules and the possibility of conjugating fluorescent dyes for bioimaging. The high near-infrared absorbance makes graphene ideal for photothermal therapy. Henceforth, graphene turns out to be a reliable multifunctional material for use in diagnosis and treatment. It exhibits antibacterial property by directly interacting with the cell membrane. Potential application of graphene as a scaffold for the attachment and proliferation of stem cells and neuronal cells is captivating in a tissue regeneration scenario. Fabrication of 2D graphene into a 3D structure is made possible with the help of 3D printing, a revolutionary technology having promising applications in tissue and organ engineering. However, apart from its advantageous application scope, use of graphene raises toxicity concerns. Several reports have confirmed the potential toxicity of graphene and its derivatives, and the inconsistency may be due to the lack of standardized consensus protocols. The present review focuses on the hidden facts of graphene and its biomedical application, with special emphasis on drug delivery, biosensing, bioimaging, antibacterial, tissue engineering, and 3D printing applications.

Investigation of chronic toxicity of hydroxyapatite nanoparticles administered orally for one year in wistar rats.

Although the toxicity/biocompatibility of hydroxyapatite nanoparticles (nano HA), a prospective nano biomaterial is extensively studied, its interaction on biological systems following chronic exposure is less exploited. In the present study, Wistar rats were given various concentrations of nano HA in the diet to determine the chronic toxicity and potential carcinogenicity. Altogether 140 rats were used for the study under various administration dosages along with control. The animals were sacrificed after 12months of controlled continuous dosing. All in-life parameters, including body weight, food consumption, clinical observations, survival, biochemical and hematology, were unaffected by the chronic exposure of nano HA orally. Similarly, gross and histopathological evaluation was also unchanged following exposure to nano HA. No evidence of nano HA-related lesions or Nano HA-induced neoplasia was suggested in this rodent bioassay study.

Safety and biocompatibility of graphene: A new generation nanomaterial for biomedical application.

Graphene, a material with great application potential is expected to revolutionize various fields in the near future particularly biomedical field with its inherent properties. However, significant increase in the research on graphene in the recent years has created anxiety about their safety/biocompatibility towards living organisms. Though there is increase in reports on graphene synthesis and application, in parallel reports on unwanted toxic effects of these materials is under scrutiny. Before exploiting their use, any engineered nanomaterials should undergo through investigation regarding the risk and health hazards imposed by them. Toxicity of nanomaterial depends on many factors like size, shape, surface chemistry, dose, duration and the biological milieu. In this account, we reviewed physico-chemical properties of graphene that plays a key role in toxicity prediction. We also detailed some examples of the in vitro and in vivo toxicity studies that have been published so far. The potential environmental risk associated with these carbon materials is also addressed, in order to avoid unintentional leaching of these materials into surface water.

Nano-biointeractions of PEGylated and bare reduced graphene oxide on lung alveolar epithelial cells: A comparative in vitro study.

Graphene and its derivatives have garnered significant scientific interest and have potential use in nano-electronics as well as biomedicine. However the undesirable biological consequence, especially upon inhalation of the particle, requires further investigations. This study aimed to elucidate the nano-biointeractions of PEGylated reduced graphene oxide (PrGO) and reduced graphene oxide (rGO) with that of lung alveolar epithelial cells (A549). Both nanomaterials showed dose dependent decrease in cell viability and alteration of cell morphology after 24h. Upon intracellular uptake of PrGO, it elicited oxidative stress mediated apoptosis in the cells by inducing ROS, loss of mitochondrial membrane potential (MMP) and inflammatory response by NF-κB activation. Conversely, rGO was found to scavenge ROS efficiently except at high dose after 24h. It was found that ROS at high dose of rGO prompted loss of MMP. rGO was found to adhere to the cell membrane, where it is assumed to bind to cell surface Toll like receptors (TLRs) thereby activating NF-κB mediated inflammatory response. All these events culminated in an increase in apoptosis of A549 cells after 24h of rGO exposure. It was also noticed that both the nanomaterials did not initiate lysosomal pathway but instead activated mitochondria mediated apoptosis. This study highlights the possible adverse toxic effect of PrGO and rGO upon inhalation and persistence of these particles in the lungs. Further research is required to comprehend the biological response of PrGO and rGO so as to advance its biomedical application and safety.

Toxicity, toxicokinetics and biodistribution of dextran stabilized Iron oxide Nanoparticles for biomedical applications.

Advancement in the field of nanoscience and technology has alarmingly raised the call for comprehending the potential health effects caused by deliberate or unintentional exposure to nanoparticles. Iron oxide magnetic nanoparticles have an increasing number of biomedical applications and hence a complete toxicological profile of the nanomaterial is therefore a mandatory requirement prior to its intended usage to ensure safety and to minimize potential health hazards upon its exposure. The present study elucidates the toxicity of in house synthesized Dextran stabilized iron oxide nanoparticles (DINP) in a regulatory perspective through various routes of exposure, its associated molecular, immune, genotoxic, carcinogenic effects and bio distribution profile. Synthesized ferrite nanomaterials were successfully coated with dextran (<25nm) and were physicochemically characterized and subjected to in vitro and in vivo toxicity evaluations. The results suggest that surface coating of ferrite nanoparticles with dextran helps in improvising particle stability in biological environments. The nanoparticles do not seem to induce oxidative stress mediated toxicological effects, nor altered physiological process or behavior changes or visible pathological lesions. Furthermore no anticipated health hazards are likely to be associated with the use of DINP and could be concluded that the synthesized DINP is nontoxic/safe to be used for biomedical applications.

Interfacing of dextran coated ferrite nanomaterials with cellular system and delayed hypersensitivity on Guinea pigs.

The study focused on the interfacing of dextran coated ferrite nanomaterials (DFNM) with the cellular system and delayed hypersensitivity on Guinea pigs. In vitro study investigated the cytotoxic potential of DFNM on L929 cells, effect on antioxidant enzymes and Lipid peroxides (LPO) production on rat brain homogenates. DFNM was also repeatedly exposed topically to Guinea pigs for the evidence of skin sensitization and toxicity at the molecular level. Biochemical and hematological parameters were estimated. Liver and brain of Guinea pigs were homogenized and evaluated for the induction of LPO, glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and 8-hydroxyl-2-deoxyguanosine (8-OHdG). The results of the study demonstrated that there was no significant alternation in the level of antioxidant defense enzymes, LPO, hematological, biochemical or oxidative stress related DNA damage. Hence, it can be concluded that the synthesized DFNM was non-skin irritant or non-toxic at the molecular level under the laboratory conditions.

An in vitro study on the interaction of hydroxyapatite nanoparticles and bone marrow mesenchymal stem cells for assessing the toxicological behaviour.

Mesenchymal stem cells or multipotent progenitor cells isolated from bone marrow presents close resemblance to the natural in vivo milieu and hence preferred more than the conventional cell culture systems to predict the toxicological behavior of bio-nano interaction. The objective of the present study is to evaluate the molecular toxicity of hydroxyapatite nanoparticles (HANPs) using mouse bone marrow mesenchymal stem cells (BMSCs). In-house synthesized HANPs (50 nm) were used to study the cytotoxicity, nano particle uptake, effect on cyto skeletal arrangement, oxidative stress response and apoptotic behavior with the confluent BMSCs as per standard protocols. The results of the MTT assay indicated that HANPs does not induce cytotoxicity up to 800 µg/mL. It was also observed that oxidative stress related apoptosis and reactive oxygen species (ROS) production following nanoparticle treatment was similar to that of control (cells without treatment). Hence it can be concluded that the in-house synthesized HANPs are non-toxic/safe at the molecular level suggesting that the HANPs are compatible to BMSCs. Further, the in vitro BMSCs cell culture can be used as a model for evaluating the preliminary toxicity of nanomaterials.

Cells-nano interactions and molecular toxicity after delayed hypersensitivity, in guinea pigs on exposure to hydroxyapatite nanoparticles.

The aim of the study was to evaluate the cells-nanoparticle interactions and molecular toxicity after delayed hypersensitivity in Guinea pigs, exposed to hydroxyapatite nanoparticles (HANP). The study focuses on synthesizing and characterizing HANPs and gaining an insight into the cytotoxicity, molecular toxicity, hypersensitivity and oxidative stress caused by them in vitro and in vivo. HANP was synthesized by chemical method and characterized by standard methods. Cytotoxicity was assessed on L929 cells by MTT assay and in vitro studies were carried out on rat liver homogenate. In vivo study was carried out by topical exposure of Guinea pigs with HANP, repeatedly, and evaluating the skin sensitization potential, blood parameters, oxidative stress in liver and brain and DNA damage (8-hydroxyl-2-deoxyguanosine: 8-OHdG) in liver. The results of the study indicated that there was no cytotoxicity (up to 600µg/mL) and oxidative damage (up to 100µg/mL), when exposed to HANPs. It was also evident that, there was no skin sensitization and oxidative damage when HANP were exposed to Guinea pigs.

Effects of sludge filtrate on the survival and reproduction of Ceriodaphnia dubia.

The objective of this study was to determine if the runoff from croplands fertilized with municipal sludge was toxic to aquatic biota and, therefore, a potential threat to either public health or the environment. Seven-day bioassays with Ceriodaphnia dubia showed that the No-Observed-Effect-Concentration (NOEC) was 24 g/L and the Lowest-Observed-Effect-Concentration (LOEC) for survival was 30 g/L for soil samples treated with 35.2 metric tonnes (MT)/ha of municipal sludge. For soil samples treated with 0 and 17.6 MT/ha of sludge, the survival rates of C. dubia were not significantly affected at concentrations of 6-30 g/L of soil. Reproduction was suppressed by 25% when daphnids were exposed to 3.3 g/L concentration of soil treated with sludge at 35.2 MT/ha. A 50% suppression of reproduction occurred when daphnids were exposed to 15 g/L concentration of soil treated with sludge at 17.6 MT/ha. A sludge application rate of 17.6 MT/ha suppressed reproduction at a treatment concentration of 18 g/L. These data indicate that the runoff from agricultural lands treated with municipal sludge has the potential to affect reproduction in daphnids and, therefore, the environment through the aquatic food chain.