{"title":"MiR-5622-3p inhibits ZCWPW1 to induce apoptosis in silica-exposed mice and spermatocyte cells.","authors":"Moxuan Zhao, Guiqing Zhou, Jingjing Wang, Yue Zhang, Jinglong Xue, Jianhui Liu, Junhong Xie, Lihua Ren, Xianqing Zhou","doi":"10.1080/17435390.2023.2223632","DOIUrl":"https://doi.org/10.1080/17435390.2023.2223632","url":null,"abstract":"<p><p>Silica nanoparticles (SiNPs) could cause damage to spermatogenesis, and microRNAs were reported to be associated with male reproduction. This research was designed to explore the toxic impacts of SiNPs induced in male reproduction through miR-5622-3p. In vivo, 60 mice were randomized into the control group and SiNPs group, in which they were exposed to SiNPs for 35 days and then recovered for 15 days. In vitro, 4 groups were set: control group, SiNPs group, SiNPs + miR-5622-3p inhibitor group, and SiNPs + miR-5622-3p inhibitor negative control (NC) group. Our research indicated SiNPs caused the apoptosis of spermatogenic cells, increased level of γ-H2AX, raised the expressions of RAD51, DMC1, 53BP1, and LC8 which were DNA damage repair relative factors, and upregulated Cleaved-Caspase-9 and Cleaved-Caspase-3 levels. Furthermore, SiNPs also elevated the expression of miR-5622-3p but downregulated the level of ZCWPW1. However, miR-5622-3p inhibitor reduced the level of miR-5622-3p, increased the level of ZCWPW1, relieved DNA damage, and depressed the activation of apoptosis pathway, thus, alleviating spermatogenic cells apoptosis caused by SiNPs. The above-mentioned results indicated that SiNPs induced DNA damage resulting in activating of DNA damage response. Meanwhile, SiNPs raised the level of miR-5622-3p targeting inhibited expression of ZCWPW1 to suppress the repair process, possibly making DNA damage so severe that leading to the failure of DNA damage repair, finally inducing the apoptosis of spermatogenic cells.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"17 4","pages":"372-384"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9800238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The effect of natural biomolecules on yttrium oxide nanoparticles from a <i>Daphnia magna</i> survival rate perspective.","authors":"Egle Kelpsiene, Tingru Chang, Aliaksandr Khort, Katja Bernfur, Inger Odnevall, Tommy Cedervall, Jing Hua","doi":"10.1080/17435390.2023.2226712","DOIUrl":"https://doi.org/10.1080/17435390.2023.2226712","url":null,"abstract":"<p><p>The attention to rare earth oxide nanoparticles (NPs), including yttrium oxide (Y<sub>2</sub>O<sub>3</sub>), has increased in many fields due to their unique structural characteristics and functional properties. The aim of our study was to investigate the mechanisms by which bio-corona formation on Y<sub>2</sub>O<sub>3</sub> NPs affects their environmental fate and toxicity. The Y<sub>2</sub>O<sub>3</sub> NPs induced toxicity to freshwater filter feeder <i>Daphnia magna</i> at particle concentrations of 1 and 10 mg/L, regardless of particle size. Interactions between naturally excreted biomolecules (e.g. protein, lipids, and polysaccharides) derived from <i>D. magna,</i> and the Y<sub>2</sub>O<sub>3</sub> NPs (30-45 nm) resulted in the formation of an eco-corona, which reduced their toxic effects toward <i>D. magna</i> at a particle concentration of 10 mg/L. No effects were observed at lower concentrations or for the other particle sizes investigated. Copper-zinc (Cu-Zn) superoxide dismutase, apolipophorins, and vitellogenin-1 proteins proved to be the most prominent proteins of the adsorbed corona, and possibly a reason for the reduced toxicity of the 30-45 nm Y<sub>2</sub>O<sub>3</sub> NPs toward <i>D. magna.</i></p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"17 4","pages":"385-399"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10169792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-06-01Epub Date: 2023-07-15DOI: 10.1080/17435390.2023.2231071
Fábio Campos, Patrícia V Silva, Amadeu M V M Soares, Roberto Martins, Susana Loureiro
{"title":"Harmonizing nanomaterial exposure methodologies in ecotoxicology: the effects of two innovative nanoclays in the freshwater microalgae <i>Raphidocelis subcapitata</i>.","authors":"Fábio Campos, Patrícia V Silva, Amadeu M V M Soares, Roberto Martins, Susana Loureiro","doi":"10.1080/17435390.2023.2231071","DOIUrl":"10.1080/17435390.2023.2231071","url":null,"abstract":"<p><p>Layered double hydroxides (LDHs) are innovative nanomaterials (NMs) with a typical nanoclay structure (height <40 nm) consisting of layers of metallic cations and hydroxides stabilized by anions and water molecules. Upon specific triggers, anions can exchange by others in the surrounding environment. Due to this stimuli-responsive behavior, LDHs are used as carriers of active ingredients in the industrial or pharmaceutical sectors. Available technical guidelines to evaluate the ecotoxicity of conventional substances do not account for the specificities of NMs, leading to inaccuracies and uncertainty. The present study aimed to assess two different exposure methodologies (serial dilutions of the stock dispersion vs. direct addition of NM powder to each concentration) on the ecotoxicological profile of different powder grain sizes of Zn-Al LDH-NO<sub>3</sub> and Cu-Al LDH-NO<sub>3</sub> (bulk, <25, 25-63, 63-125, 125-250, and >250 µm) in the growth of the freshwater microalgae <i>Raphidocelis subcapitata</i>. Results revealed that the serial dilutions methodology was preferable for Zn-Al LDH-NO<sub>3</sub>, whereas for Cu-Al LDH-NO<sub>3</sub> both methodologies were suitable. Thus, the serial dilutions methodology was selected to assess the ecotoxicity of different grain sizes for both LDHs. All Zn-Al LDH-NO<sub>3</sub> grain sizes yielded similar toxicity, while Cu-Al LDH-NO<sub>3</sub> powders with smaller grain sizes caused a higher effect on microalgae growth; thus, grain size separation might be advantageous for future applications of Cu-Al LDH-NO<sub>3</sub>s. Considering the differences between exposure methodologies for the Zn-Al LDH-NO<sub>3</sub>, further research involving other NMs and species must be carried out to achieve harmonization and validation for inter-laboratory comparison.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"401-419"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9878847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-06-01Epub Date: 2023-09-11DOI: 10.1080/17435390.2023.2252899
Mokarameh Pudineh Moarref, Mojtaba Alimolaei, Tara Emami, Mohammad Kazem Koohi
{"title":"Development and evaluation of cell membrane-based biomimetic nanoparticles loaded by <i>Clostridium perfringens</i> epsilon toxin: a novel vaccine delivery platform for <i>Clostridial</i>-associated diseases.","authors":"Mokarameh Pudineh Moarref, Mojtaba Alimolaei, Tara Emami, Mohammad Kazem Koohi","doi":"10.1080/17435390.2023.2252899","DOIUrl":"10.1080/17435390.2023.2252899","url":null,"abstract":"<p><p>As <i>Clostridium perfringens</i> (<i>C. perfringens</i>) epsilon toxin (ETX) ranks as the third most potent clostridial toxin after botulinum and tetanus toxins, vaccination is necessary for creatures that can be affected by it to be safe from the effects of this toxin. Nowadays, nanostructures are good choices for carriers for biological environments. We aimed to synthesize biomimetic biodegradable nanodevices to enhance the efficiency of the ETX vaccine. For this purpose, poly(lactic-co-glycolic acid) (PLGA) copolymer loaded with purified epsilon protoxin (proETX) to create nanoparticles called nanotoxins (NTs) and then coated by RBC membrane-derived vesicles (RVs) to form epsilon nanotoxoids (RV-NTs). The resulting RV-NTs shaped smooth spherical surfaces with double-layer core/shell structure with an average particle size of 105.9 ± 35.1 nm and encapsulation efficiency of 97.5% ± 0.13%. Compared with NTs, the RV-NTs were more stable for 15 consecutive days. In addition, although both structures showed a long-term cumulative release, the release rates from RV-NTs were slower than NTs during 144 hours. According to the results of cell viability, ETX loading in PLGA and entrapment in the RBC membrane decreased the toxicity of the toxin. The presence of PLGA enhances the uptake of proETX, and the synthesized structures showed no significant lesion after injection. These results demonstrate that NTs and RV-NTs could serve as an effective vaccine platform to deliver ETX for future <i>in vivo</i> assays.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"420-431"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10206476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-06-01DOI: 10.1080/17435390.2023.2210664
Julien Vignard, Aurelie Pettes-Duler, Eric Gaultier, Christel Cartier, Laurent Weingarten, Antje Biesemeier, Tatjana Taubitz, Philippe Pinton, Cecilia Bebeacua, Laurent Devoille, Jacques Dupuy, Elisa Boutet-Robinet, Nicolas Feltin, Isabelle P Oswald, Fabrice H Pierre, Bruno Lamas, Gladys Mirey, Eric Houdeau
{"title":"Food-grade titanium dioxide translocates across the buccal mucosa in pigs and induces genotoxicity in an <i>in vitro</i> model of human oral epithelium.","authors":"Julien Vignard, Aurelie Pettes-Duler, Eric Gaultier, Christel Cartier, Laurent Weingarten, Antje Biesemeier, Tatjana Taubitz, Philippe Pinton, Cecilia Bebeacua, Laurent Devoille, Jacques Dupuy, Elisa Boutet-Robinet, Nicolas Feltin, Isabelle P Oswald, Fabrice H Pierre, Bruno Lamas, Gladys Mirey, Eric Houdeau","doi":"10.1080/17435390.2023.2210664","DOIUrl":"https://doi.org/10.1080/17435390.2023.2210664","url":null,"abstract":"<p><p>The whitening and opacifying agent titanium dioxide (TiO<sub>2</sub>) is used worldwide in various foodstuffs, toothpastes and pharmaceutical tablets. Its use as a food additive (E171 in EU) has raised concerns for human health. Although the buccal mucosa is the first area exposed, oral transmucosal passage of TiO<sub>2</sub> particles has not been documented. Here we analyzed E171 particle translocation <i>in vivo</i> through the pig buccal mucosa and <i>in vitro</i> on human buccal TR146 cells, and the effects on proliferating and differentiated TR146 cells. In the buccal floor of pigs, isolated TiO<sub>2</sub> particles and small aggregates were observed 30 min after sublingual deposition, and were recovered in the submandibular lymph nodes at 4 h. In TR146 cells, kinetic analyses showed high absorption capacities of TiO<sub>2</sub> particles. The cytotoxicity, genotoxicity and oxidative stress were investigated in TR146 cells exposed to E171 in comparison with two TiO<sub>2</sub> size standards of 115 and 21 nm in diameter. All TiO<sub>2</sub> samples were reported cytotoxic in proliferating cells but not following differentiation. Genotoxicity and slight oxidative stress were reported for the E171 and 115 nm TiO<sub>2</sub> particles. These data highlight the buccal mucosa as an absorption route for the systemic passage of food-grade TiO<sub>2</sub> particles. The greater toxicity on proliferating cells suggest potential impairement of oral epithelium renewal. In conclusion, this study emphasizes that buccal exposure should be considered during toxicokinetic studies and for risk assessment of TiO<sub>2</sub> in human when used as food additive, including in toothpastes and pharmaceutical formulations.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"17 4","pages":"289-309"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-06-01DOI: 10.1080/17435390.2023.2221728
Niels Hadrup, Nicklas Sahlgren, Nicklas R Jacobsen, Anne T Saber, Karin S Hougaard, Ulla Vogel, Keld A Jensen
{"title":"Toxicity dose descriptors from animal inhalation studies of 13 nanomaterials and their bulk and ionic counterparts and variation with primary particle characteristics.","authors":"Niels Hadrup, Nicklas Sahlgren, Nicklas R Jacobsen, Anne T Saber, Karin S Hougaard, Ulla Vogel, Keld A Jensen","doi":"10.1080/17435390.2023.2221728","DOIUrl":"https://doi.org/10.1080/17435390.2023.2221728","url":null,"abstract":"<p><p>This study collects toxicity data from animal inhalation studies of some nanomaterials and their bulk and ionic counterparts. To allow potential grouping and interpretations, we retrieved the primary physicochemical and exposure data to the extent possible for each of the materials. Reviewed materials are compounds (mainly elements, oxides and salts) of carbon (carbon black, carbon nanotubes, and graphene), silver, cerium, cobalt, copper, iron, nickel, silicium (amorphous silica and quartz), titanium (titanium dioxide), and zinc (chemical symbols: Ag, C, Ce, Co, Cu, Fe, Ni, Si, Ti, TiO<sub>2</sub>, and Zn). Collected endpoints are: a) pulmonary inflammation, measured as neutrophils in bronchoalveolar lavage (BAL) fluid at 0-24 hours after last exposure; and b) genotoxicity/carcinogenicity. We present the dose descriptors no-observed-adverse-effect concentrations (NOAECs) and lowest-observed-adverse-effect concentrations (LOAECs) for 88 nanomaterial investigations in data-library and graph formats. We also calculate 'the value where 25% of exposed animals develop tumors' (T25) for carcinogenicity studies. We describe how the data may be used for hazard assessment of the materials using carbon black as an example. The collected data also enable hazard comparison between different materials. An important observation for poorly soluble particles is that the NOAEC for neutrophil numbers in general lies around 1 to 2 mg/m<sup>3</sup>. We further discuss why some materials' dose descriptors deviate from this level, likely reflecting the effects of the ionic form and effects of the fiber-shape. Finally, we discuss that long-term studies, in general, provide the lowest dose descriptors, and dose descriptors are positively correlated with particle size for near-spherical materials.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"17 4","pages":"338-371"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9853221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-06-01DOI: 10.1080/17435390.2023.2218925
Barbara Wójcik, Katarzyna Zawadzka, Sławomir Jaworski, Marta Kutwin, Malwina Sosnowska, Agnieszka Ostrowska, Marta Grodzik, Artur Małolepszy, Marta Mazurkiewicz-Pawlicka, Mateusz Wierzbicki
{"title":"Dependence of diamond nanoparticle cytotoxicity on physicochemical parameters: comparative studies of glioblastoma, breast cancer, and hepatocellular carcinoma cell lines.","authors":"Barbara Wójcik, Katarzyna Zawadzka, Sławomir Jaworski, Marta Kutwin, Malwina Sosnowska, Agnieszka Ostrowska, Marta Grodzik, Artur Małolepszy, Marta Mazurkiewicz-Pawlicka, Mateusz Wierzbicki","doi":"10.1080/17435390.2023.2218925","DOIUrl":"https://doi.org/10.1080/17435390.2023.2218925","url":null,"abstract":"<p><p>Reports on the cytotoxicity of diamond nanoparticles (ND) are ambiguous and depend on the physicochemical properties of the material and the tested cell lines. Thus, the aim of this research was to evaluate the influence of thirteen types of diamond nanoparticles, differing in production method, size, and surface functional groups, on their cytotoxicity against four tumor cell lines (T98G, U-118 MG, MCF-7, and Hep G2) and one non-tumor cell line (HFF-1). In order to understand the dependence of diamond nanoparticles on physicochemical properties, the following parameters were analyzed: viability, cell membrane damage, morphology, and the level of intracellular general ROS and mitochondrial superoxide. The performed analyses revealed that all diamond nanoparticles showed no toxicity to MCF-7, Hep G2, and HFF-1 cells. In contrast, the same nanomaterials were moderately toxic for the glioblastoma T98G and U-118 MG cell lines. In general, the effect of the production method did not influence ND toxicity. Some changes in cell response after treatment with modified nanomaterials were observed, with the presence of carboxyl groups having a more detrimental effect than the presence of other functional groups. Although nanoparticles of different sizes caused similar toxicity, nanomaterials with bigger particles caused a more pronounced effect.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"17 4","pages":"310-337"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-06-01Epub Date: 2023-10-17DOI: 10.1080/17435390.2023.2265465
Adriana Rodríguez-Garraus, Clara Passerino, Gerard Vales, Michela Carlin, Satu Suhonen, Aurelia Tubaro, Julio Gómez, Marco Pelin, Julia Catalán
{"title":"Impact of physico-chemical properties on the toxicological potential of reduced graphene oxide in human bronchial epithelial cells.","authors":"Adriana Rodríguez-Garraus, Clara Passerino, Gerard Vales, Michela Carlin, Satu Suhonen, Aurelia Tubaro, Julio Gómez, Marco Pelin, Julia Catalán","doi":"10.1080/17435390.2023.2265465","DOIUrl":"10.1080/17435390.2023.2265465","url":null,"abstract":"<p><p>The increasing use of graphene-based materials (GBM) requires their safety evaluation, especially in occupational settings. The same physico-chemical (PC) properties that confer GBM extraordinary functionalities may affect the potential toxic response. Most toxicity assessments mainly focus on graphene oxide and rarely investigate GBMs varying only by one property. As a novelty, the present study assessed the in vitro cytotoxicity and genotoxicity of six reduced graphene oxides (rGOs) with different PC properties in the human bronchial epithelial 16HBE14o - cell line. Of the six materials, rGO1-rGO4 only differed in the carbon-to-oxygen (C/O) content, whereas rGO5 and rGO6 were characterized by different lateral size and number of layers, respectively, but similar C/O content compared with rGO1. The materials were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, laser diffraction and dynamic light scattering, and Brunauer-Emmett-Teller analysis. Cytotoxicity (Luminescent Cell Viability and WST-8 assays), the induction of reactive oxygen species (ROS; 2',7'-dichlorofluorescin diacetate-based assay), the production of cytokines (enzyme-linked immunosorbent assays) and genotoxicity (comet and micronucleus assays) were evaluated. Furthermore, the internalization of the materials in the cells was confirmed by laser confocal microscopy. No relationships were found between the C/O ratio or the lateral size and any of the rGO-induced biological effects. However, rGO of higher oxygen content showed higher cytotoxic and early ROS-inducing potential, whereas genotoxic effects were observed with the rGO of the lowest density of oxygen groups. On the other hand, a higher number of layers seems to be associated with a decreased potential for inducing cytotoxicity and ROS production.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"471-495"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41166896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2023-04-01DOI: 10.1080/17435390.2023.2204161
Chol Seung Lim, Brandon Veltri, Michael Kashon, Dale W Porter, Qiang Ma
{"title":"Multi-walled carbon nanotubes induce arachidonate 5-lipoxygenase expression and enhance the polarization and function of M1 macrophages <i>in vitro</i>.","authors":"Chol Seung Lim, Brandon Veltri, Michael Kashon, Dale W Porter, Qiang Ma","doi":"10.1080/17435390.2023.2204161","DOIUrl":"https://doi.org/10.1080/17435390.2023.2204161","url":null,"abstract":"<p><p>Fibrogenic carbon nanotubes (CNTs) induce the polarization of M1 and M2 macrophages in mouse lungs. Polarization of the macrophages regulates the production of proinflammatory and pro-resolving lipid mediators (LMs) to mediate acute inflammation and its resolution in a time-dependent manner. Here we examined the molecular mechanism by which multi-walled CNTs (MWCNTs, Mitsui-7) induce M1 polarization <i>in vitro</i>. Treatment of murine macrophages (J774A.1) with Mitsui-7 MWCNTs increased the expression of Alox5 mRNA and protein in a concentration- and time-dependent manner. The MWCNTs induced the expression of CD68 and that induction persisted for up to 3 days post-exposure. The expression and activity of inducible nitric oxide synthase, an intracellular marker of M1, were increased by MWCNTs. Consistent with M1 polarization, the MWCNTs induced the production and secretion of proinflammatory cytokines tumor necrosis factor-α and interleukin-1β, and proinflammatory LMs leukotriene B4 (LTB4) and prostaglandin E2 (PGE2). The cell-free media from MWCNT-polarized macrophages induced the migration of neutrophilic cells (differentiated from HL-60), which was blocked by Acebilustat, a specific leukotriene A4 hydrolase inhibitor, or LY239111, an LTB4 receptor antagonist, but not NS-398, a cyclooxygenase 2 inhibitor, revealing LTB4 as a major mediator of neutrophil chemotaxis from MWCNT-polarized macrophages. Knockdown of Alox5 using specific small hairpin-RNA suppressed MWCNT-induced M1 polarization, LTB4 secretion, and migration of neutrophils. Taken together, these findings demonstrate the polarization of M1 macrophages by Mitsui-7 MWCNTs <i>in vitro</i> and that induction of Alox5 is an important mechanism by which the MWCNTs promote proinflammatory responses by boosting M1 polarization and production of proinflammatory LMs.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"17 3","pages":"249-269"},"PeriodicalIF":5.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10263170/pdf/nihms-1899756.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9678401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhanced toxicity of 2,2-bis(chloromethyl) trimethylene bis[bis(2-chloroethyl) phosphate] (V6) by nanopolystyrene particles towards HeLa cells.","authors":"Zheng Zhong, Xin Liu, Yiming Ruan, Ziwei Li, Junxian Li, Lili Sun, Sen Hou","doi":"10.1080/17435390.2023.2203238","DOIUrl":"https://doi.org/10.1080/17435390.2023.2203238","url":null,"abstract":"<p><p>2,2-bis(chloromethyl) trimethylene bis[bis(2-chloroethyl) phosphate] (V6) has been widely used as an additive in a variety of plastics due to its extremely low toxicity. However, we showed in the study that once mixed with nanopolystyrene particles (NPs), the nontoxic V6 could exhibit significant toxicity to HeLa cells. The enhanced toxicity was much higher than the toxicity of NPs alone and was related to the size of NPs. The mixture of V6 and small polystyrene NPs (10 nm and 15 nm in radius) showed obvious toxicity to HeLa cells. The toxicity increased with the concentrations of both V6 and NPs. On the contrary, the mixture of V6 and larger NPs (25 nm, 50 nm, 100 nm, and 500 nm in radius) showed almost no toxicity even at extremely high concentrations (NPs: 100 mg/L; V6: 50 mg/L). The small NPs could enter the cells and accumulated in cytoplasm. However, the larger NPs did not distribute inside the cells. NPs efficiently adsorbed V6 on the surface. The mechanism of the enhanced toxicity was attributed to the increased intracellular reactive oxygen species (ROS) production and the regulation of gene expression concerning apoptosis and ROS scavenging. Our study not only showed that a safe chemical V6 could be turned to be toxic by NPs, but also pointed out a potential risk caused by the joint toxicity of 'safe' chemicals and plastic particles with small size.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"17 3","pages":"203-217"},"PeriodicalIF":5.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9459184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}