Oxidative stress contributes to cobalt oxide nanoparticles-induced cytotoxicity and DNA damage in human hepatocarcinoma cells.

BackgroundCobalt oxide nanoparticles (Co(3)O(4)NPs) are increasingly recognized for their utility in biological applications, magnetic resonance imaging, and drug delivery. However, little is known about the toxicity of Co(3)O(4)NPs in human cells.MethodsWe investigated the possible mechanisms of genotoxicity induced by Co(3)O(4)NPs in human hepatocarcinoma (HepG2) cells. Cell viability, reactive oxygen species (ROS), glutathione, thiobarbituric acid reactive substance, apoptosis, and DNA damage were assessed in HepG2 cells after Co(3)O(4)NPs and Co(2+) exposure.ResultsCo(3)O(4)NPs elicited a significant (P < 0.01) reduction in glutathione with a concomitant increase in lipid hydroperoxide, ROS generation, superoxide dismutase, and catalase activity after 24- and 48-hour exposure. Co(3)O(4)NPs had a mild cytotoxic effect in HepG2 cells; however, it induced ROS and oxidative stress, leading to DNA damage, a probable mechanism of genotoxicity. The comet assay showed a statistically significant (P < 0.01) dose- and time-related increase in DNA damage for Co(3)O(4)NPs, whereas Co(2+) induced less change than Co(3)O(4)NPs but significantly more than control.ConclusionOur results demonstrated that Co(3)O(4)NPs induced cytotoxicity and genotoxicity in HepG2 cells through ROS and oxidative stress

Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species

Mohd Javed Akhtar1,2, Maqusood Ahamed3, Sudhir Kumar1, MA Majeed Khan3, Javed Ahmad4, Salman A Alrokayan31Department of Zoology, University of Lucknow, Lucknow, India; 2Fibre Toxicology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India; 3King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia; 4Department of Zoology, College of Science, King Saud University, Riyadh, Saudi ArabiaBackground: Zinc oxide nanoparticles (ZnO NPs) have received much attention for their implications in cancer therapy. It has been reported that ZnO NPs induce selective killing of cancer cells. However, the underlying molecular mechanisms behind the anticancer response of ZnO NPs remain unclear.Methods and results: We investigated the cytotoxicity of ZnO NPs against three types of cancer cells (human hepatocellular carcinoma HepG2, human lung adenocarcinoma A549, and human bronchial epithelial BEAS-2B) and two primary rat cells (astrocytes and hepatocytes). Results showed that ZnO NPs exert distinct effects on mammalian cell viability via killing of all three types of cancer cells while posing no impact on normal rat astrocytes and hepatocytes. The toxicity mechanisms of ZnO NPs were further investigated using human liver cancer HepG2 cells. Both the mRNA and protein levels of tumor suppressor gene p53 and apoptotic gene bax were upregulated while the antiapoptotic gene bcl-2 was downregulated in ZnO NP-treated HepG2 cells. ZnO NPs were also found to induce activity of caspase-3 enzyme, DNA fragmentation, reactive oxygen species generation, and oxidative stress in HepG2 cells.Conclusion: Overall, our data demonstrated that ZnO NPs selectively induce apoptosis in cancer cells, which is likely to be mediated by reactive oxygen species via p53 pathway, through which most of the anticancer drugs trigger apoptosis. This study provides preliminary guidance for the development of liver cancer therapy using ZnO NPs.Keywords: ZnO nanoparticles, cancer therapy, p53, apoptosis, RO

Structural Characterisation and Assessment of the Novel Bacillus amyloliquefaciens RK3 Exopolysaccharide on the Improvement of Cognitive Function in Alzheimer’s Disease Mice

In this study Bacillus amyloliquefaciens RK3 was isolated from a sugar mill effluent-contaminated soil and utilised to generate a potential polysaccharide with anti-Alzheimer’s activity. Traditional and molecular methods were used to validate the strain. The polysaccharide produced by B. amyloliquefaciens RK3 was purified, and the yield was estimated to be 10.35 gL−1. Following purification, the polysaccharide was structurally and chemically analysed. The structural analysis revealed the polysaccharide consists of α-d-mannopyranose (α-d-Manp) and β-d-galactopyranose (β-d-Galp) monosaccharide units connected through glycosidic linkages (i.e, β-d-Galp(1→6)β-d-Galp (1→6)β-d-Galp(1→2)β-d-Galp(1→2)[β-d-Galp(1→6)]β-d-Galp(1→2)α-d-Manp(1→6)α-d-Manp (1→6)α-d-Manp(1→6)α-d-Manp(1→6)α-d-Manp). The scanning electron microscopy and energy-dispersive X-ray spectroscopy imaging of polysaccharides emphasise their compactness and branching in the usual tubular heteropolysaccharide structure. The purified exopolysaccharide significantly impacted the plaques formed by the amyloid proteins during Alzheimer’s disease. Further, the results also highlighted the potential applicability of exopolysaccharide in various industrial and pharmaceutical applications

Synthesis and characterization of some abundant nanoparticles, their antimicrobial and enzyme inhibition activity

Although the antimicrobial activity of the engineered nanoparticles (NPs) is well known, the biochemical mechanisms underlying this activity are not clearly understood. Therefore, four NPs with the highest global production, namely SiO2, TiO2, ZnO, and Ag, were synthesized and characterized. The synthesized SiO2, TiO2, ZnO, and Ag NPs exhibit an average size of 11.12, 13.4, 35, and 50 nm, respectively. The antimicrobial activity of the synthesized NPs against bacteria and fungi were also determined. NPs-mediated inhibition of two very important enzymes, namely urease and DNA polymerase, is also reported. The synthesized NPs especially Ag and ZnO show significant antimicrobial activity against bacteria and fungi including methicillin-resistant Staphylococcus aureus even at low concentration. The DNA polymerase activity was inhibited at a very low concentration range of 2–4 µg/ml, whereas the urease activity was inhibited at a high concentration range of 50–100 µg/ml. Based on their ability to inhibit the urease and DNA polymerase, NPs can be arranged in the following order: Ag > ZnO > SiO2 > TiO2 and Ag > SiO2 > ZnO > TiO2, respectively. As the synthesized NPs inhibit bacterial growth and suppress the activity of urease and DNA polymerase, the use of these NPs to control pathogens is proposed

Structural and thermal studies of silver nanoparticles and electrical transport study of their thin films

This work reports the preparation and characterization of silver nanoparticles synthesized through wet chemical solution method and of silver films deposited by dip-coating method. X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), field emission transmission electron microscopy (FETEM), high-resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED), and energy dispersive spectroscopy (EDX) have been used to characterize the prepared silver nanoparticles and thin film. The morphology and crystal structure of silver nanoparticles have been determined by FESEM, HRTEM, and FETEM. The average grain size of silver nanoparticles is found to be 17.5 nm. The peaks in XRD pattern are in good agreement with that of face-centered-cubic form of metallic silver. TGA/DTA results confirmed the weight loss and the exothermic reaction due to desorption of chemisorbed water. The temperature dependence of resistivity of silver thin film, determined in the temperature range of 100-300 K, exhibit semiconducting behavior of the sample. The sample shows the activated variable range hopping in the localized states near the Fermi level

Barium Titanate (BaTiO3) Nanoparticles Exert Cytotoxicity through Oxidative Stress in Human Lung Carcinoma (A549) Cells

Barium titanate (BaTiO3) nanoparticles (BT NPs) have shown exceptional characteristics such as high dielectric constant and suitable ferro-, piezo-, and pyro-electric properties. Thus, BT NPs have shown potential to be applied in various fields including electro-optical devices and biomedicine. However, very limited knowledge is available on the interaction of BT NPs with human cells. This work was planned to study the interaction of BT NPs with human lung carcinoma (A549) cells. Results showed that BT NPs decreased cell viability in a dose- and time-dependent manner. Depletion of mitochondrial membrane potential and induction of caspase-3 and -9 enzyme activity were also observed following BT NP exposure. BT NPs further induced oxidative stress indicated by induction of pro-oxidants (reactive oxygen species and hydrogen peroxide) and reduction of antioxidants (glutathione and several antioxidant enzymes). Moreover, BT NP-induced cytotoxicity and oxidative stress were effectively abrogated by N-acetyl-cysteine (an ROS scavenger), suggesting that BT NP-induced cytotoxicity was mediated through oxidative stress. Intriguingly, the underlying mechanism of cytotoxicity of BT NPs was similar to the mode of action of ZnO NPs. At the end, we found that BT NPs did not affect the non-cancerous human lung fibroblasts (IMR-90). Altogether, BT NPs selectively induced cytotoxicity in A549 cells via oxidative stress. This work warrants further research on selective cytotoxicity mechanisms of BT NPs in different types of cancer cells and their normal counterparts

Evaluation of the Cytotoxicity and Oxidative Stress Response of CeO2-RGO Nanocomposites in Human Lung Epithelial A549 Cells

Graphene-based nanocomposites have attracted enormous interest in nanomedicine and environmental remediation, owing to their unique characteristics. The increased production and widespread application of these nanocomposites might raise concern about their adverse health effects. In this study, for the first time, we examine the cytotoxicity and oxidative stress response of a relatively new nanocomposite of cerium oxide-reduced graphene oxide (CeO2-RGO) in human lung epithelial (A549) cells. CeO2-RGO nanocomposites and RGO were prepared by a simple hydrothermal method and characterized by relevant analytical techniques. Cytotoxicity data have shown that RGO significantly induces toxicity in A549 cells, evident by cell viability reduction, membrane damage, cell cycle arrest, and mitochondrial membrane potential loss. However, CeO2-RGO nanocomposites did not cause statistically significant toxicity as compared to a control. We further observed that RGO significantly induces reactive oxygen species generation and reduces glutathione levels. However, CeO2-RGO nanocomposites did not induce oxidative stress in A549 cells. Interestingly, we observed that CeO2 nanoparticles (NPs) alone significantly increase glutathione (GSH) levels in A549 cells as compared to a control. The GSH replenishing potential of CeO2 nanoparticles could be one of the possible reasons for the biocompatible nature of CeO2-RGO nanocomposites. Our data warrant further and more advanced research to explore the biocompatibility/safety mechanisms of CeO2-RGO nanocomposites in different cell lines and animal models

Enhanced Photocatalytic and Anticancer Activity of Zn-Doped BaTiO₃ Nanoparticles Prepared through a Green Approach Using Banana Peel Extract

Perovskite barium titanate (BaTiO3) has received a lot of interest due to its extraordinary dielectric and ferroelectric properties, along with its moderate biocompatibility. Here, we investigated how Zn doping tuned the physicochemical characteristics, photocatalytic activity, and anticancer potential of BaTiO3 nanoparticles synthesized from banana peel extract. XRD, TEM, SEM, EDS, XPS, BET, Raman, and PL were utilized to characterize the as-synthesized pure and Zn (1 and 3 mol%)-doped BaTiO3 nanoparticles. All of the synthesized samples showed evidence of the BaTiO3 tetragonal phase, and the XRD patterns of the Zn-doped BaTiO3 nanoparticles showed the presence of a Zn peak. The particle size of BaTiO3 decreased with increasing levels of Zn doping without morphological changes. After Zn doping, the PL intensity of BaTiO3 decreased, suggesting a lower electron–hole recombination rate. BET analysis found that the surface area of Zn-doped BaTiO3 nanoparticles was higher than that of pure BaTiO3. Under visible irradiation, the photocatalytic activity of pure and Zn-doped BaTiO3 nanoparticles was compared, and a remarkable 85% photocatalytic activity of Zn (3%)-doped BaTiO3 nanoparticles was measured. As a result, Zn-doped BaTiO3 nanoparticles are recognized as excellent photocatalysts for degrading organic pollutants. According to cytotoxicity data, Zn (3%)-doped BaTiO3 nanoparticles display four-fold greater anticancer activity against human lung carcinoma (A549) than pure BaTiO3 nanoparticles. It was also observed that Zn-doped BaTiO3 nanoparticles kill cancer cells by increasing the intracellular level of reactive oxygen species. Furthermore, compared to pure BaTiO3, the Zn-doped BaTiO3 nanostructure showed better cytocompatibility in non-cancerous human lung fibroblasts (IMR90). The Zn-doped BaTiO3 nanoparticles have a reduced particle size, increased surface area, and a lower electron–hole recombination rate, which are highly beneficial for enhanced photocatalytic and anticancer activity. Overall, current data showed that green-fabricated Zn-BaTiO3 nanoparticles have superior photocatalytic and anticancer effects along with improved biocompatibility compared to those of pure BaTiO3. This work underlines the significance of utilizing agricultural waste (e.g., fruit peel) for the fabrication of BaTiO3-based nanostructures, which hold great promise for biomedical and environmental applications

Fish mucus mediated biosynthesis of copper oxide nanoparticles: spectral characterization, morphology and biological activity

Simple methodology was developed to synthesize copper oxide nanoparticles (CuO NPs) using mucus of Channa striatus ( C. striatus ). The mucus of C. striatus is known for its biological properties due to the presence of numerous amino acids. This mucus was used as stabilizing agent for CuO NPs synthesis from copper acetate. The prepared CuO NPs were characterized by fourier transforms infrared spectrometer (FTIR), powder x-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), energy dispersive x-ray analysis (EDX) and transmission electron microscope (TEM) coupled with selected area diffraction pattern (SAED). The FTIR study suggested the utilization of mucus in the synthesis of CuO NPs. The XRD data also confirmed formation of pure crystalline phase of CuO NPs. Fish mucus stabilized CuO NPs exhibited significant activity against HeLa cells. The results of cell death clearly indicated that the synthesized CuO nanoparticles could be served as a biomaterial for anticancer treatment

Anti-Inflammatory CeO2 Nanoparticles Prevented Cytotoxicity Due to Exogenous Nitric Oxide Donors via Induction Rather Than Inhibition of Superoxide/Nitric Oxide in HUVE Cells

The mechanism behind the cytoprotective potential of cerium oxide nanoparticles (CeO2 NPs) against cytotoxic nitric oxide (NO) donors and H2O2 is still not clear. Synthesized and characterized CeO2 NPs significantly ameliorated the lipopolysaccharide (LPS)-induced cytokines IL-1β and TNF-α. The main goal of this study was to determine the capacities of NPs regarding signaling effects that could have occurred due to reactive oxygen species (ROS) and/or NO, since NP-induced ROS/NO did not lead to toxicity in HUVE cells. Concentrations that induced 50% cell death (i.e., IC50s) of two NO donors (DETA-NO; 1250 ± 110 µM and sodium nitroprusside (SNP); 950 ± 89 µM) along with the IC50 of H2O2 (120 ± 7 µM) were utilized to evaluate cytoprotective potential and its underlying mechanism. We determined total ROS (as a collective marker of hydrogen peroxide, superoxide radical (O2•−), hydroxyl radical, etc.) by DCFH-DA and used a O2•− specific probe DHE to decipher prominent ROS. The findings revealed that signaling effects mediated mainly by O2•− and/or NO are responsible for the amelioration of toxicity by CeO2 NPs at 100 µg/mL. The unaltered effect on mitochondrial membrane potential (MMP) due to NP exposure and, again, CeO2 NPs-mediated recovery in the loss of MMP due to exogenous NO donors and H2O2 suggested that NP-mediated O2•− production might be extra-mitochondrial. Data on activated glutathione reductase (GR) and unaffected glutathione peroxidase (GPx) activities partially explain the mechanism behind the NP-induced gain in GSH and persistent cytoplasmic ROS. The promoted antioxidant capacity due to non-cytotoxic ROS and/or NO production, rather than inhibition, by CeO2 NP treatment may allow cells to develop the capacity to tolerate exogenously induced toxicity