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

Thermal Model of Rotary Friction Welding for Similar and Dissimilar Metals

Friction welding is one of the foremost welding processes for similar and dissimilar metals. Previously, the process has been modeled utilizing the rudimentary techniques of constant friction and slip-stick friction. The motivation behind this article is to present a new characteristic for temperature profile estimation in modeling of the rotary friction welding process. For the first time, a unified model has been exhibited, with an implementation of the phase transformation of similar and dissimilar materials. The model was generated on COMSOL Multiphysics® and thermal and structural modules were used to plot the temperature curve. The curve for the welding of dissimilar metals using the model was generated, compared and analyzed with that of practical curves already acquired through experimentation available in the literature, and then the effect of varying the parameters on the welding of similar metals was also studied

A facile one-pot synthesis of novel 2,5-disubstituted-1,3,4-oxadiazoles under conventional and microwave conditions and evaluation of their in vitro antimicrobial activities

AbstractA rapid and efficient solvent-free synthesis of 2,5-disubstituted-1,3,4-oxadiazoles (3a–l) from fatty acid hydrazides (1a–f) under microwave irradiation is described. The structural elucidation of these compounds is based on their spectral data (IR, 1H NMR, 13C NMR and MS). All the newly synthesized compounds have been screened for their antibacterial and antifungal activities. The compounds 3f, 3j and 3l were found to be most potent anti-microbial agents

Evaluation of cytotoxicity and oxidative stress induced by alcoholic extract and oil of Lepidium Sativum seeds in human liver cell line HepG2

Since, the primary site of drug metabolism is the liver, that plays a major role in metabolism, digestion, detoxification, and elimination of substances from the body, the present studies were designed to investigate the possible adverse effect of alcoholic extract of seeds of Lepidium sativum (LSA) and Lepidium sativum seed oil (LSO) on HepG2 cells, a human liver cell line. LSA and LSO induced cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and neutral red uptake (NRU) assays. Morphological changes, lipid peroxidation, glutathione, catalase, and superoxide dismutase activities in HepG2 cells were studied. Cells were exposed to 25 to 1000 μg/ml of LSA and LSO for 24 h. The results show that LSA and LSO reduced cell viability, and altered the cellular morphology in dose dependent manner. Concentrations (100 to 1000 μg/ml) of LSA and LSO were found to be cytotoxic, whereas 50 μg/ml and lower concentrations did not cause any significant adverse effect in cell viability of HepG2 cells. LSA and LSO were also found to induce oxidative stress in dosedependent manner indicated by decrease in glutathione level, catalase activity, and SOD activity and an increase in lipid peroxidation. The results indicate that LSA and LSO induced oxidative stress mediated cytotoxicity in HepG2 cells.Keywords: Lepidium sativum, HepG2 cells, oxidative stress, cytoxicityAfrican Journal of Biotechnology Vol. 12(24), pp. 3854-386

Portulaca oleracea Linn seed extract ameliorates hydrogen peroxide-induced cell death in human liver cells by inhibiting reactive oxygen species generation and oxidative stress

Purpose: To investigate the protective effects of Portulaca oleracea seed extract (POA) against cytotoxicity, oxidative stress and reactive oxygen species (ROS) generation induced by hydrogen peroxide (H2O2) in human liver cells (HepG2).Methods: The extract (POA) was obtained by ethanol extraction of P. oleracea seeds. Cytotoxicity in HepG2 cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, neutral red uptake (NRU) assay and morphological changes. The cells were pre-exposed to noncytotoxic concentrations (5 - 25 μg/mL) of POA for 24 h, and then cytotoxic (0.25 mM) concentration of H2O2. After 24 h of exposure, MTT and NRU assays were used to evaluate cell viability, while morphological changes were assessed using phase contrast inverted microscopy. The effect of POA on reduced glutathione (GSH) level, lipid peroxidation (LPO), and ROS generation induced by H2O2 was also studied.Results: The results showed that pre-exposure to POA (25 μg/mL) significantly (p <0.01) attenuated the loss of cell viability by up to 38 % against H2O2-induced oxidative stress and ROS generation. In addition, POA (25 μg/mL) significantly (p <0.01) increased GSH level (31 %), but decreased the levels of LPO (37 %) and ROS generation (49 %).Conclusion: This study demonstrates that POA has the capacity to protect HepG2 cells against H2O2- induced cell death by inhibiting oxidative stress and ROS generation.Keywords: Portulaca oleracea, HepG2 cells, Cytotoxicity, Oxidative stress, Reactive oxygen specie

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

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Cytotoxicity and apoptosis induction of zinc ferrite nanoparticle through the oxidative stress pathway in human breast cancer cells

The nanoparticles of Zinc ferrite have been broadly used in various fields such as solar cells, photocatalysis, hydrogen storage, sensors etc. Here, the zinc ferrite nanoparticles (ZnFe2O4NPs) was prepared via solution process and characterized in detail with instruments such as XRD, FESEM, TEM, FTIR and TGA. The characterization studies revealed that the average individual size of each NP is ∼ 27 ± 1 nm size. The FTIR shows the functional band of metal and oxygen was obtained at 570 cm−1. Although, the processing and use of zinc iron oxide based nanostructures are very widely utilized in industries but a limited studies are available towards the biological studies. The current work explores the application of ZnFe2O4NPs with the concentration range from 2 to 200 μg/mL against breast cancer cells (MCF-7) to examine the cytotoxicity of oxidative stress and morphological variations using MTT, NRU, LPO, GSH assays after 24 h of treatment. Dose dependent drop in cell survival was seen in MTT and NRU assays. A significant increase in LPO was observed in MCF-7 cells exposed to ZnFe2O4NPs after 24 h of treatment. However, the GSH levels in MCF-7 cells exposed to ZnFe2O4NPs decreased significantly after 24 h. Further, the study of apoptotic gene expression was seen by real time PCR analysis was also conducted and described