Nanotoxicology最新文献

{"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,&nbsp;Aurelie Pettes-Duler,&nbsp;Eric Gaultier,&nbsp;Christel Cartier,&nbsp;Laurent Weingarten,&nbsp;Antje Biesemeier,&nbsp;Tatjana Taubitz,&nbsp;Philippe Pinton,&nbsp;Cecilia Bebeacua,&nbsp;Laurent Devoille,&nbsp;Jacques Dupuy,&nbsp;Elisa Boutet-Robinet,&nbsp;Nicolas Feltin,&nbsp;Isabelle P Oswald,&nbsp;Fabrice H Pierre,&nbsp;Bruno Lamas,&nbsp;Gladys Mirey,&nbsp;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 (TiO₂) 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 TiO₂ 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 TiO₂ 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 TiO₂ particles. The cytotoxicity, genotoxicity and oxidative stress were investigated in TR146 cells exposed to E171 in comparison with two TiO₂ size standards of 115 and 21 nm in diameter. All TiO₂ samples were reported cytotoxic in proliferating cells but not following differentiation. Genotoxicity and slight oxidative stress were reported for the E171 and 115 nm TiO₂ particles. These data highlight the buccal mucosa as an absorption route for the systemic passage of food-grade TiO₂ 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 TiO₂ 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}

{"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,&nbsp;Nicklas Sahlgren,&nbsp;Nicklas R Jacobsen,&nbsp;Anne T Saber,&nbsp;Karin S Hougaard,&nbsp;Ulla Vogel,&nbsp;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, TiO₂, 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/m³. 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}

{"title":"Dependence of diamond nanoparticle cytotoxicity on physicochemical parameters: comparative studies of glioblastoma, breast cancer, and hepatocellular carcinoma cell lines.","authors":"Barbara Wójcik,&nbsp;Katarzyna Zawadzka,&nbsp;Sławomir Jaworski,&nbsp;Marta Kutwin,&nbsp;Malwina Sosnowska,&nbsp;Agnieszka Ostrowska,&nbsp;Marta Grodzik,&nbsp;Artur Małolepszy,&nbsp;Marta Mazurkiewicz-Pawlicka,&nbsp;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}

{"title":"Impact of physico-chemical properties on the toxicological potential of reduced graphene oxide in human bronchial epithelial cells.","authors":"Adriana Rodríguez-Garraus,&nbsp;Clara Passerino,&nbsp;Gerard Vales,&nbsp;Michela Carlin,&nbsp;Satu Suhonen,&nbsp;Aurelia Tubaro,&nbsp;Julio Gómez,&nbsp;Marco Pelin,&nbsp;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}

{"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,&nbsp;Brandon Veltri,&nbsp;Michael Kashon,&nbsp;Dale W Porter,&nbsp;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,&nbsp;Xin Liu,&nbsp;Yiming Ruan,&nbsp;Ziwei Li,&nbsp;Junxian Li,&nbsp;Lili Sun,&nbsp;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}

{"title":"Needlelike, short and thin multi-walled carbon nanotubes: comparison of effects on wild type and p53^+/- rat lungs.","authors":"Hélène Barthel,&nbsp;Sylvie Sébillaud,&nbsp;Mylène Lorcin,&nbsp;Henrik Wolff,&nbsp;Stéphane Viton,&nbsp;Frédéric Cosnier,&nbsp;Laurent Gaté,&nbsp;Carole Seidel","doi":"10.1080/17435390.2023.2204933","DOIUrl":"https://doi.org/10.1080/17435390.2023.2204933","url":null,"abstract":"<p><p>Carbon nanotubes (CNTs) are nanomaterials presenting an occupational inhalation risk during production or handling. The International Agency for Research on Cancer classified one CNT, Mitsui-7 (MWNT-7), as 'possibly carcinogenic to humans'. In recognition of their similarities, a proposal has been submitted to the risk assessment committee of ECHA to classify all fibers with 'Fibre Paradigm' (FP)-compatible dimensions as carcinogenic. However, there is a lack of clarity surrounding the toxicity of fibers that do not fit the FP criteria. In this study, we compared the effects of the FP-compatible Mitsui-7, to those of NM-403, a CNT that is too short and thin to fit the paradigm. Female Sprague Dawley rats deficient for p53 (GMO) and wild type (WT) rats were exposed to the two CNTs (0.25 mg/rat/week) by intratracheal instillation. Animals (GMO and WT) were exposed weekly for four consecutive weeks and were sacrificed 3 days or 8 months after the last instillation. Exposure to both CNTs induced acute lung inflammation. However, persistent inflammation at 8 months was only observed in the lungs of rats exposed to NM-403. In addition to the persistent inflammation, NM-403 stimulated hyperplasic changes in rat lungs, and no adenomas or carcinomas were detected. The degree and extent of hyperplasia was significantly more pronounced in GMO rats. These results suggest that CNT not meeting the FP criteria can cause persistent inflammation and hyperplasia. Consequently, their health effects should be carefully assessed.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"17 3","pages":"270-288"},"PeriodicalIF":5.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9863831","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":"Assessing regulated cell death modalities as an efficient tool for <i>in vitro</i> nanotoxicity screening: a review.","authors":"Anton Tkachenko,&nbsp;Anatolii Onishchenko,&nbsp;Valeriy Myasoedov,&nbsp;Svetlana Yefimova,&nbsp;Ondrej Havranek","doi":"10.1080/17435390.2023.2203239","DOIUrl":"https://doi.org/10.1080/17435390.2023.2203239","url":null,"abstract":"<p><p>Nanomedicine is a fast-growing field of nanotechnology. One of the major obstacles for a wider use of nanomaterials for medical application is the lack of standardized toxicity screening protocols for assessing the safety of newly synthesized nanomaterials. In this review, we focus on less frequently studied nanomaterials-induced regulated cell death (RCD) modalities, including eryptosis, necroptosis, pyroptosis, and ferroptosis, as a tool for <i>in vitro</i> nanomaterials safety evaluation. We summarize the latest insights into the mechanisms that mediate these RCDs in response to nanomaterials exposure. Comprehensive data from reviewed studies suggest that ROS (reactive oxygen species) overproduction and ROS-mediated pathways play a central role in nanomaterials-induced RCDs activation. On the other hand, studies also suggest that individual properties of nanomaterials, including size, shape, or surface charge, could determine specific toxicity pathways with consequent RCD induction as well. We anticipate that the evaluation of RCDs can become one of the mechanism-based screening methods in nanotoxicology. In addition to the toxicity assessment, evaluation of necroptosis-, pyroptosis-, and ferroptosis-promoting capacity of nanomaterials could simultaneously provide useful information for specific medical applications as could be their anti-tumor potential. Moreover, a detailed understanding of molecular mechanisms driving nanomaterials-mediated induction of immunogenic RCDs will substantially aid novel anti-tumor nanodrugs development.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"17 3","pages":"218-248"},"PeriodicalIF":5.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9458679","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":"Algal extracellular polymeric substances (algal-EPS) for mitigating the combined toxic effects of polystyrene nanoplastics and nano-TiO₂ in <i>Chlorella</i> sp.","authors":"Lokeshwari Natarajan,&nbsp;M Annie Jenifer,&nbsp;Willie J G M Peijnenburg,&nbsp;Amitava Mukherjee","doi":"10.1080/17435390.2023.2179438","DOIUrl":"https://doi.org/10.1080/17435390.2023.2179438","url":null,"abstract":"<p><p>The continuous release of nanoparticles and nanoplastics into the marine environment necessitates the examination of their combined effects in marine organisms. Natural Organic Matter (NOM) can significantly influence the behavior of nanomaterials in the marine environment. The present study explores the effects of algal Extracellular Polymeric Substances (EPS) in reducing the combined toxic effects of three different polystyrene nanoplastics (PSNPs)- aminated (NH₂-PSNPs), carboxylated (COOH-PSNPs), and plain PSNPs - and P25 titanium dioxide nanoparticles (Nano-TiO₂) towards the marine alga, <i>Chlorella</i> sp. Two doses (0.25 and 2.5 mg/L) of nano-TiO₂ mixed with the PSNPs (1 mg/L) were employed. The COOH-PSNPs with 2.5 mg/L nano-TiO₂ exhibited higher growth inhibition toward algal cells. Addition of algal EPS to the mixture of NMs decreased the negative effect significantly. The mean hydrodynamic diameter increased significantly from 666 to 797 nm and 1248 to 3589 nm at concentrations 0.25 and 2.5 mg/L, respectively when the mixtures of nano-TiO₂ and COOH-PSNPs were incubated with the algal EPS. In comparison to the pristine NMs, the EPS-NMs were found to significantly reduce the superoxide and hydroxyl radical production. The results were further validated with the estimation of lipid peroxidation (LPO), esterase activity, photosynthetic efficiency, and membrane permeability in the cells. The major outcomes from this study highlight the role of algal EPS in significantly reducing the toxic impact of binary mixture of NMs in marine organisms.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"17 2","pages":"143-156"},"PeriodicalIF":5.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9460717","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":"Ferritinophagy was involved in long-term SiNPs exposure induced ferroptosis and liver fibrosis.","authors":"Qingqing Liang,&nbsp;Yuexiao Ma,&nbsp;Fenghong Wang,&nbsp;Mengqi Sun,&nbsp;Lisen Lin,&nbsp;Tianyu Li,&nbsp;Junchao Duan,&nbsp;Zhiwei Sun","doi":"10.1080/17435390.2023.2197055","DOIUrl":"https://doi.org/10.1080/17435390.2023.2197055","url":null,"abstract":"<p><p>SiNPs could induce liver fibrosis<i>invivo</i>, but the mechanism was not completely clear. This study focused on exploring whether long-term SiNPs exposure at human-related exposure dosage could lead to ferritinophagy-mediated ferroptosis and liver fibrosis. <i>In vivo</i>, long-term SiNPs exposure induced liver fibrosis inrats accompanied by ferritinophagy and ferroptosis in hepatocytes. Interestingly, the progression of liver fibrosis was alleviated after exposure cessation and recovery, meanwhile ferritinophagy and ferroptosis were not further activated. <i>In vitro</i>, after long-term SiNPs exposure, the mitochondrial membrane ruptured, lipid peroxidation intensified, the level of redox active iron increased and the repair protein of lipid peroxidation were consumed in L-02 cells, demonstrating ferroptosis occurrence. Notably, <i>NCOA4</i> knockdown inhibited ferritin degradation, alleviated the increase of intracellular ferrous iron level, reduced lipid peroxidation and the depletion of glutathione peroxidase 4 (GPX4). In conclusion, ferritinophagy mediated by NCOA4 was responsible for long-term SiNPs exposure induced hepatocytes ferroptosis and liver fibrosis, which provided a scientific basis for toxicological assessment of SiNPs and would be benefited for the safety design of SiNPs-based products.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"17 2","pages":"157-175"},"PeriodicalIF":5.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9827086","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}