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1.
NanoImpact ; 27: 100414, 2022 07.
Article in English | MEDLINE | ID: mdl-35961501

ABSTRACT

Graphene nanoplatelet (GNP) as a nanofiller improves the mechanical strength, electrical conductivity, and flame retardancy of the polymers significantly. With an increasing number of GNP-reinforced products, a careful safety assessment is needed to avoid social and economic setbacks. However, no study has addressed the effects of combustion-generated emissions from GNP-reinforced products in the lung, the most sensitive exposure route to airborne particles. Therefore, we studied the influence of GNP as a nanofiller on the emitted particles and polycyclic aromatic hydrocarbons (PAHs), and cytotoxicity of the emissions from the combustion of pure epoxy (EP) and GNP-reinforced epoxy (EP-GNP). GNP was not detected in the airborne emissions. PAHs were found in airborne particles of both emissions from EP and EP-GNP, with some differences in their concentrations. A first hazard assessment was performed on human alveolar epithelial cells exposed to the airborne emissions at air-liquid interface conditions. At 24 h and 96 h after the exposure, similar responses were observed between EP and EP-GNP except an acute transient decrease in mitochondrial activity after exposure to the emissions from EP-GNP. Both emissions from EP and EP-GNP had no acute effects on membrane integrity, cell morphology or expression of anti-oxidative stress markers (HMOX1 and SOD2 genes). Meanwhile, both emissions induced the activation of the aryl hydrocarbon receptor (CYP1A1 gene) and a transient (pro-) inflammatory response (MCP-1), but the effects between EP and EP-GNP were not significantly different.


Subject(s)
Air Pollutants , Graphite , Polycyclic Aromatic Hydrocarbons , Air Pollutants/analysis , Graphite/toxicity , Humans , Lung/chemistry , Polycyclic Aromatic Hydrocarbons/toxicity , Vehicle Emissions/analysis
2.
Anal Biochem ; 637: 114449, 2022 01 15.
Article in English | MEDLINE | ID: mdl-34762874

ABSTRACT

Nanoparticles have been used as antibacterial agents in several products. To optimize their effectiveness, synthesis processes and particle modifications have been developed, creating the need for a rapid screening method to investigate their potencies. Owing to the opacity and insolubility of nanoparticles, a classical method to determine antibacterial activity-such as the minimum inhibitory concentration (MIC), which relies on turbidimetry-might not apply to them. In this study, we demonstrate the potential of a dye (resazurin)-based assay as an indicator of bacterial growth to rapidly screen the antibacterial activities of both organic and inorganic nanomaterials against both gram-negative (E. coli) and gram-positive (S. aureus) bacteria. The results indicate that the resazurin-based assay successfully determine the MIC of organic lipid nanocarriers, and several inorganic nanoparticles. However, the use of resazurin require a precaution for nanoparticles with photocatalytic properties, which may cause dye degradation at higher concentrations. In this study, resazurin bleaching was observed at approximately >50 mg/ml of TiO2. In summary, the modified MIC assay with resazurin can evaluate antibacterial activity of nanomaterials, whose turbidity interferer conventional MIC assay. This modification conserves an advantage of MICs assay which are simple and reliable. This would be useful for screening of antibacterial nanomaterials.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Escherichia coli/drug effects , Nanoparticles/administration & dosage , Oxazines/chemistry , Staphylococcus aureus/drug effects , Xanthenes/chemistry , Anti-Bacterial Agents/chemistry , Indicators and Reagents/chemistry , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests/methods , Nanoparticles/chemistry , Nephelometry and Turbidimetry/methods , Oils, Volatile/chemistry , Particle Size , Silver/chemistry , Titanium/chemistry , Zinc Oxide/chemistry
3.
Micromachines (Basel) ; 14(1)2022 Dec 22.
Article in English | MEDLINE | ID: mdl-36677084

ABSTRACT

Dynamic gut-on-a-chip platform allows better recreation of the intestinal environment in vitro compared to the traditional static cell culture. However, the underlying mechanism is still not fully discovered. In this study, the shear stress behavior in a gut-on-a-chip device with porous membrane subjected to peristalsis motion is numerically investigated using CFD simulation for three different pore sizes and two pattern layouts. The results reveal that, in the stationary microchannel, the average shear stress on the porous membrane is approximately 15% greater than that of the flat membrane, regardless of the pore size. However, when subjected to cyclic deformation, the porous membrane with smaller pore size experiences stronger variation of shear stress which is ±5.61%, ±10.12% and ±34.45% from its average for the pore diameters of 10 µm, 5 µm and 1 µm, respectively. The shear stress distribution is more consistent in case of the staggered pattern layout while the in-line pattern layout allows for a 32% wider range of shear stress at the identical pore size during a cyclic deformation. These changes in the shear stress caused by peristalsis motion, porous size and membrane pattern could be the key factors that promote cell differentiation in the deforming gut-on-a-chip model.

4.
Sci Rep ; 11(1): 3234, 2021 02 05.
Article in English | MEDLINE | ID: mdl-33547413

ABSTRACT

Gut-on-chip devices enable exposure of cells to a continuous flow of culture medium, inducing shear stresses and could thus better recapitulate the in vivo human intestinal environment in an in vitro epithelial model compared to static culture methods. We aimed to study if dynamic culture conditions affect the gene expression of Caco-2 cells cultured statically or dynamically in a gut-on-chip device and how these gene expression patterns compared to that of intestinal segments in vivo. For this we applied whole genome transcriptomics. Dynamic culture conditions led to a total of 5927 differentially expressed genes (3280 upregulated and 2647 downregulated genes) compared to static culture conditions. Gene set enrichment analysis revealed upregulated pathways associated with the immune system, signal transduction and cell growth and death, and downregulated pathways associated with drug metabolism, compound digestion and absorption under dynamic culture conditions. Comparison of the in vitro gene expression data with transcriptome profiles of human in vivo duodenum, jejunum, ileum and colon tissue samples showed similarities in gene expression profiles with intestinal segments. It is concluded that both the static and the dynamic gut-on-chip model are suitable to study human intestinal epithelial responses as an alternative for animal models.


Subject(s)
Gene Expression Profiling/instrumentation , Intestinal Mucosa/metabolism , Lab-On-A-Chip Devices , Transcriptome , Caco-2 Cells , Cell Culture Techniques/instrumentation , Equipment Design , Humans , Intestinal Mucosa/cytology
5.
Nanotoxicology ; 15(9): 1233-1252, 2021 11.
Article in English | MEDLINE | ID: mdl-35077654

ABSTRACT

Due to the widespread application of food-relevant inorganic nanomaterials, the gastrointestinal tract is potentially exposed to these materials. Gut-on-chip in vitro systems are proposed for the investigation of compound toxicity as they better recapitulate the in vivo human intestinal environment than static models, due to the added shear stresses associated with the flow of the medium. We aimed to compare cellular responses of intestinal epithelial Caco-2 cells at the gene expression level upon TiO2 (E171) and ZnO (NM110) nanomaterial exposure when cultured under dynamic and conventionally applied static conditions. Whole-genome transcriptome analyses upon exposure of the cells to TiO2 and ZnO nanomaterials revealed differentially expressed genes and related biological processes that were culture condition specific. The total number of differentially expressed genes (p < 0.01) and affected pathways (p < 0.05 and FDR < 0.25) after nanomaterial exposure was higher under dynamic culture conditions than under static conditions for both nanomaterials. The observed increase in nanomaterial-induced responses in the gut-on-chip model indicates that shear stress might be a major factor in cell susceptibility. This is the first report on the application of a gut-on-chip system in which gene expression responses upon TiO2 and ZnO nanomaterial exposure are evaluated and compared to a static system. It extends current knowledge on nanomaterial toxicity assessment and the influence of a dynamic environment on cellular responses. Application of the gut-on-chip system resulted in higher sensitivity of the cells and might thus be an attractive system for use in the toxicological hazard characterization of nanomaterials.


Subject(s)
Nanostructures , Zinc Oxide , Caco-2 Cells , Humans , Nanostructures/toxicity , Titanium/toxicity , Transcriptome , Zinc Oxide/toxicity
6.
Toxicol In Vitro ; 65: 104815, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32119998

ABSTRACT

Dynamic flow in vitro models are currently widely explored for their applicability in drug development research. The application of gut-on-chip models in toxicology is lagging behind. Here we report the application of a gut-on-chip model for biokinetic studies and compare the observed biokinetics of reference compounds with those obtained using a conventional static in vitro model. Intestinal epithelial Caco-2 cells were cultured on a porous membrane assembled between two glass flow chambers for the dynamic model, or on a porous membrane in a Transwell model. Confocal microscopy, lucifer yellow translocation, and alkaline phosphatase activity evaluation revealed that cells cultured in the gut-on-chip model formed tight, differentiated, polarized monolayers like in the static cultures. In the dynamic gut-on-chip model the transport of the high permeability compounds antipyrine, ketoprofen and digoxin was lower (i.e. 4.2-, 2.7- and 1.9-fold respectively) compared to the transport in the static Transwell model. The transport of the low permeability compound, amoxicillin, was similar in both the dynamic and static in vitro model. The obtained transport values of the compounds are in line with the compound Biopharmaceuticals Classification System. It is concluded that the gut-on-chip provides an adequate model for transport studies of chemicals.


Subject(s)
Intestinal Mucosa/metabolism , Lab-On-A-Chip Devices , Pharmaceutical Preparations/metabolism , Biological Transport , Caco-2 Cells , Cell Differentiation , Cell Survival , Epithelial Cells/metabolism , Humans
7.
RSC Adv ; 8(57): 32440-32453, 2018 Sep 18.
Article in English | MEDLINE | ID: mdl-35547722

ABSTRACT

Novel microfluidic technologies allow the manufacture of in vitro organ-on-a-chip systems that hold great promise to adequately recapitulate the biophysical and functional complexity of organs found in vivo. In this study, a gut-on-a-chip model was developed aiming to study the potential cellular association and transport of food contaminants. Intestinal epithelial cells (Caco-2) were cultured on a porous polyester membrane that was tightly clamped between two glass slides to form two separate flow chambers. Glass syringes, polytetrafluoroethylene tubing and glass microfluidic chips were selected to minimize surface adsorption of the studied compounds (i.e. highly lipophilic dioxins), during the transport studies. Confocal microscopy studies revealed that, upon culturing under constant flow for 7 days, Caco-2 cells formed complete and polarized monolayers as observed after culturing for 21 days under static conditions in Transwells. We exposed Caco-2 monolayers in the chip and Transwell to a mixture of 17 dioxin congeners (7 polychlorinated dibenzo-p-dioxins and 10 polychlorinated dibenzofurans) for 24 h. Gas chromatography-high resolution mass spectrometry was used to assess the cellular association and transport of individual dioxin congeners across the Caco-2 cell monolayers. After 24 h, the amount of transported dioxin mixture was similar in both the dynamic gut-on-a-chip model and the static Transwell model. The transport of individual congeners corresponded with their number of chlorine atoms and substitution patterns as revealed by quantitative structure-property relationship modelling. These results show that the gut-on-a-chip model can be used, as well as the traditional static Transwell system, to study the cellular association and transport of lipophilic compounds like dioxins.

8.
Drug Metab Pharmacokinet ; 31(3): 210-7, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27212065

ABSTRACT

Effects of the hydroethanolic extract of Phikud Navakot (PN), a Thai traditional remedy, on human cytochrome P450s (CYPs) were investigated in vitro. Selective substrates of CYPs were used to investigate the effects and kinetics of PN on CYP inhibition using human liver microsomes. Primary human hepatocytes were used to assess the inductive effects of PN on CYP enzyme activities and protein expressions. The results showed that PN inhibited the activities of CYP1A2, CYP2C9, CYP2D6, and CYP3A4 with half maximal inhibitory concentration (IC50) values of 13, 62, 67, and 88 µg/mL, respectively. Meanwhile, it had no effect on the activities of CYP2C19 and CYP2E1 (IC50 > 1 mg/mL). PN exhibited competitive inhibition of CYP1A2 (Ki = 34 µg/mL), mixed type inhibition of CYP2C9 and CYP2D6 (Ki = 80 and 12 µg/mL, respectively), and uncompetitive inhibition of CYP3A4 (Ki = 150 µg/mL). PN did not have an inductive effect on CYP1A2, CYP2C9, CYP2C19 and CYP3A4 in primary human hepatocytes, which is an advantageous characteristic of the extract. However the extract may cause herb-drug interactions via inhibition of CYP1A2, CYP2C9, CYP2D6 and CYP3A4, and precautions should be taken when PN is coadministered with drugs that are metabolized by these CYP enzymes.


Subject(s)
Cytochrome P-450 Enzyme Inducers/pharmacology , Cytochrome P-450 Enzyme Inhibitors/pharmacology , Cytochrome P-450 Enzyme System/metabolism , Plant Extracts/pharmacology , Cells, Cultured , Cytochrome P-450 Enzyme Inhibitors/toxicity , Hepatocytes/drug effects , Hepatocytes/enzymology , Humans , Kinetics , Plant Extracts/toxicity
9.
Article in English | MEDLINE | ID: mdl-26001102

ABSTRACT

Silver has distinct antibacterial properties and has been used as a component of commercial products with many applications. An increasing number of commercial products cause risks of silver effects for human and environment such as the symptoms of Argyria and the release of silver to the environment. Therefore, the detection of silver in the aquatic environment is important. The colorimetric chemosensor is designed by the basic of ligand interactions with metal ion, leading to the change of signals for the naked-eyes which is very useful method to this application. Dithizone ligand is considered as one of the effective chelating reagents for metal ions due to its high selectivity and sensitivity of a photochromic reaction for silver as well as the linear backbone of dithizone affords the rotation of various isomeric forms. The present study is focused on the conformation and interaction of dithizone with silver using density functional theory (DFT). The interaction parameters were determined in term of binding energy of complexes and the geometry optimization, frequency of the structures and calculation of binding energies using density functional approaches B3LYP and the 6-31G(d,p) basis set. Moreover, the interaction of silver-dithizone complexes was supported by UV-Vis spectroscopy, FT-IR spectrum that were simulated by using B3LYP/6-31G(d,p) and (1)H NMR spectra calculation using B3LYP/6-311+G(2d,p) method compared with the experimental data. The results showed the ion exchange interaction between hydrogen of dithizone and silver atom with minimized binding energies of silver-dithizone interaction. Therefore, the results can be the useful information for determination of complex interaction using the analysis of computer simulations.


Subject(s)
Dithizone/chemistry , Magnetic Resonance Spectroscopy , Models, Molecular , Quantum Theory , Silver/chemistry , Anions , Dimethyl Sulfoxide/chemistry , Ligands , Solutions , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Thermodynamics
10.
Toxicol In Vitro ; 27(1): 330-8, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22940466

ABSTRACT

Silver nanoparticles (AgNPs) are incorporated into a large number of consumer and medical products. Several experiments have demonstrated that AgNPs can be toxic to the vital organs of humans and especially to the lung. The present study evaluated the in vitro mechanisms of AgNP (<100 nm) toxicity in relationship to the generation of reactive oxygen species (ROS) in A549 cells. AgNPs caused ROS formation in the cells, a reduction in their cell viability and mitochondrial membrane potential (MMP), an increase in the proportion of cells in the sub-G1 (apoptosis) population, S phase arrest and down-regulation of the cell cycle associated proliferating cell nuclear antigen (PCNA) protein, in a concentration- and time-dependent manner. Pretreatment of the A549 cells with N-acetyl-cysteine (NAC), an antioxidant, decreased the effects of AgNPs on the reduced cell viability, change in the MMP and proportion of cells in the sub-G1population, but had no effect on the AgNP-mediated S phase arrest or down-regulation of PCNA. These observations allow us to propose that the in vitro toxic effects of AgNPs on A549 cells are mediated via both ROS-dependent (cytotoxicity) and ROS-independent (cell cycle arrest) pathways.


Subject(s)
Metal Nanoparticles/toxicity , Silver/toxicity , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Humans , Membrane Potential, Mitochondrial/drug effects , Proliferating Cell Nuclear Antigen/metabolism , Reactive Oxygen Species/metabolism
11.
Biol Trace Elem Res ; 149(1): 123-32, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22528773

ABSTRACT

Titanium dioxide nanoparticles (TiO(2)NPs) are increasingly being used in various industrial applications including the production of paper, plastics, cosmetics and paints. With the increasing number of nano-related products, the concern of governments and the general public about the health and environmental risks, especially with regard to occupational and other environmental exposure, are gradually increasing. However, there is insufficient knowledge about the actual affects upon human health and the environment, as well as a lack of suitable biomarkers for assessing TiO(2)NP-induced cytotoxicity. Since the respiratory tract is likely to be the main exposure route of industrial workers to TiO(2)NPs, we investigated the cytotoxicity of the anatase and rutile crystalline forms of TiO(2)NPs in A549 cells, a human alveolar type II-like epithelial cell line. In addition, we evaluated the transcript and protein expression levels of two heat shock protein (HSP) members, Grp78 and Hsp70, to ascertain their suitability as biomarkers of TiO(2)NP-induced toxicity in the respiratory system. Ultrastructural observations confirmed the presence of TiO(2)NPs inside cells. In vitro exposure of A549 cells to the anatase or rutile forms of TiO(2)NPs led to cell death and induced intracellular ROS generation in a dose-dependent manner, as determined by the MTS and dichlorofluorescein (DCF) assays, respectively. In contrast, the transcript and protein expression levels of Hsp70 and Grp78 did not change within the same TiO(2)NPs dose range (25-500 µg/ml). Thus, whilst TiO(2)NPs can cause cytotoxicity in A549 cells, and thus potentially in respiratory cells, Hsp70 and Grp78 are not suitable biomarkers for evaluating the acute toxicological effects of TiO(2)NPs in the respiratory system.


Subject(s)
Bronchi/metabolism , Epithelial Cells/metabolism , HSP70 Heat-Shock Proteins/metabolism , Heat-Shock Proteins/metabolism , Metal Nanoparticles/toxicity , Titanium/toxicity , Biomarkers/metabolism , Bronchi/pathology , Cell Death , Cell Line, Tumor , Dose-Response Relationship, Drug , Endoplasmic Reticulum Chaperone BiP , Environmental Monitoring/methods , Epithelial Cells/pathology , Epithelial Cells/ultrastructure , Fluoresceins/metabolism , Gene Expression Regulation , HSP70 Heat-Shock Proteins/genetics , Heat-Shock Proteins/genetics , Humans , Microscopy, Electron, Transmission , Protein Biosynthesis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , Titanium/metabolism , Toxicity Tests/methods
12.
Xenobiotica ; 42(9): 854-62, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22458323

ABSTRACT

Silver nanoparticles (AgNPs) are increasingly used in various products and consequentially the potential adverse effects associated with exposure to them are of concern. This study investigated the effects of AgNPs on the hepatic drug-metabolizing enzymes of the cytochrome P450 (CYP) families 1, 2 and 3, using both in vitro and in vivo biological assays. AgNPs were orally administered to Sprague-Dawley rats at various concentrations (0-1000 mg/kg body weight/day) for 2 weeks. No effect was found on the plasma levels of ALT, AST and ALP in all treated rat groups, and no significant change in the activities of CYP1A, CYP2C, CYP2D, CYP2E1 and CYP3A was observed for all tested AgNP doses. The results correlated with the observation that no AgNPs were detected in the liver sections of the tested rats. However, the in vitro system using rat liver microsomes demonstrated a strong inhibition of CYP2C (IC(50) = 28 µg/mL) and CYP2D (IC(50) = 23 µg/mL) activities, but not of CYP1A, CYP2E1 and CYP3A activities (IC(50) > 100 µg/mL) at concentrations up to 100 µg/mL of AgNPs. The inhibitory effect of AgNPs on these CYPs indicates the possibility of the AgNP-drug interaction when co-administered with some medicines and this may cause adverse effects to patients.


Subject(s)
Cytochrome P-450 Enzyme System/drug effects , Liver/enzymology , Metal Nanoparticles/adverse effects , Silver/toxicity , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Analysis of Variance , Animals , Aspartate Aminotransferases/blood , Cytochrome P-450 Enzyme System/metabolism , Inhibitory Concentration 50 , Metal Nanoparticles/toxicity , Microscopy, Electron, Transmission , Microsomes, Liver/metabolism , Rats , Rats, Sprague-Dawley
13.
Part Fibre Toxicol ; 7: 8, 2010 Apr 01.
Article in English | MEDLINE | ID: mdl-20359338

ABSTRACT

Silver nanoparticles have been used in numerous commercial products, including textiles, to prevent bacterial growth. Meanwhile, there is increasing concern that exposure to these nanoparticles may cause potential adverse effects on humans as well as the environment. This study determined the quantity of silver released from commercially claimed nanosilver and laboratory-prepared silver coated fabrics into various formulations of artificial sweat, each made according to AATCC, ISO and EN standards. For each fabric sample, the initial amount of silver and the antibacterial properties against the model Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria on each fabric was investigated. The results showed that silver was not detected in some commercial fabrics. Furthermore, antibacterial properties of the fabrics varied, ranging from 0% to greater than 99%. After incubation of the fabrics in artificial sweat, silver was released from the different fabrics to varying extents, ranging from 0 mg/kg to about 322 mg/kg of fabric weight. The quantity of silver released from the different fabrics was likely to be dependent on the amount of silver coating, the fabric quality and the artificial sweat formulations including its pH. This study is the unprecedented report on the release of silver nanoparticles from antibacterial fabrics into artificial sweat. This information might be useful to evaluate the potential human risk associated with the use of textiles containing silver nanoparticles.


Subject(s)
Anti-Bacterial Agents/analysis , Anti-Infective Agents, Local , Metal Nanoparticles/analysis , Silver/analysis , Sweat/chemistry , Textiles/analysis , Anti-Bacterial Agents/toxicity , Escherichia coli/drug effects , Materials Testing , Metal Nanoparticles/toxicity , Microbial Sensitivity Tests , Silver/toxicity , Staphylococcus aureus/drug effects , Textiles/microbiology
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