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Santoni M, Piccinini G, Liguori G, Randi MR, Baroncini M, Milani L, Danesi F. Enhanced intestinal epithelial co-culture model with orbital mechanical stimulation: a proof-of-concept application in food nanotoxicology. Front Mol Biosci 2025; 11:1529027. [PMID: 39872165 PMCID: PMC11769796 DOI: 10.3389/fmolb.2024.1529027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 12/19/2024] [Indexed: 01/29/2025] Open
Abstract
Introduction Current in vitro intestinal models lack the mechanical forces present in the physiological environment, limiting their reliability for nanotoxicology studies. Here, we developed an enhanced Caco-2/HT29-MTX-E12 co-culture model incorporating orbital mechanical stimulation to better replicate intestinal conditions and investigate nanoparticle interactions. Methods We established co-cultures under static and dynamic conditions, evaluating their development through multiple approaches including barrier integrity measurements, gene expression analysis, and confocal microscopy. We introduced novel quantitative analysis of dome formation as a differentiation marker and demonstrated the model application by investigating cellular responses to titanium dioxide (TiO₂) nanoparticles in a digested food matrix. Results Dynamic conditions accelerated epithelial differentiation, achieving functional barrier properties by day 14 rather than day 21, with enhanced mucin production and more organized three-dimensional structure. Mechanical stimulation selectively promoted goblet cell differentiation without affecting general epithelial markers. The optimized model successfully detected concentration-dependent oxidative stress responses to TiO₂ exposure, revealing cellular dysfunction preceding membrane damage. Discussion This improved co-culture system provides a better physiological platform for nanotoxicology studies. By incorporating mechanical forces, each cell type exhibits more representative behavior, creating a more realistic experimental setup. The model bridges the gap between simple monocultures and complex 3D systems, offering a practical approach for investigating nanoparticle-epithelium interactions in a food-relevant context.
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Affiliation(s)
- Mattia Santoni
- Department of Agricultural and Food Sciences (DISTAL), University of Bologna, Cesena, Italy
| | - Giovanni Piccinini
- Department of Agricultural and Food Sciences (DISTAL), University of Bologna, Cesena, Italy
- Department of Biological, Geological, and Environmental Sciences (BiGeA), University of Bologna, Bologna, Italy
| | - Giovanni Liguori
- Department of Biological, Geological, and Environmental Sciences (BiGeA), University of Bologna, Bologna, Italy
| | - Maria Roberta Randi
- Department of Biological, Geological, and Environmental Sciences (BiGeA), University of Bologna, Bologna, Italy
| | - Massimo Baroncini
- Department of Agricultural and Food Sciences (DISTAL), University of Bologna, Cesena, Italy
| | - Liliana Milani
- Department of Biological, Geological, and Environmental Sciences (BiGeA), University of Bologna, Bologna, Italy
| | - Francesca Danesi
- Department of Agricultural and Food Sciences (DISTAL), University of Bologna, Cesena, Italy
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Wu J, Gupta G, Buerki-Thurnherr T, Nowack B, Wick P. Bridging the gap: Innovative human-based in vitro approaches for nanomaterials hazard assessment and their role in safe and sustainable by design, risk assessment, and life cycle assessment. NANOIMPACT 2024; 36:100533. [PMID: 39454678 DOI: 10.1016/j.impact.2024.100533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 10/22/2024] [Accepted: 10/22/2024] [Indexed: 10/28/2024]
Abstract
The application of nanomaterials in industry and consumer products is growing exponentially, which has pressed the development and use of predictive human in vitro models in pre-clinical analysis to closely extrapolate potential toxic effects in vivo. The conventional cytotoxicity investigation of nanomaterials using cell lines from cancer origin and culturing them two-dimensionally in a monolayer without mimicking the proper pathophysiological microenvironment may affect a precise prediction of in vitro effects at in vivo level. In recent years, complex in vitro models (also belonging to the new approach methodologies, NAMs) have been established in unicellular to multicellular cultures either by using cell lines, primary cells or induced pluripotent stem cells (iPSCs), and reconstituted into relevant biological dimensions mimicking in vivo conditions. These advanced in vitro models retain physiologically reliant exposure scenarios particularly appropriate for oral, dermal, respiratory, and intravenous administration of nanomaterials, which have the potential to improve the in vivo predictability and lead to reliable outcomes. In this perspective, we discuss recent developments and breakthroughs in using advanced human in vitro models for hazard assessment of nanomaterials. We identified fit-for-purpose requirements and remaining challenges for the successful implementation of in vitro data into nanomaterials Safe and Sustainable by Design (SSbD), Risk Assessment (RA), and Life Cycle Assessment (LCA). By addressing the gap between in vitro data generation and the utility of in vitro data for nanomaterial safety assessments, a prerequisite for SSbD approaches, we outlined potential key areas for future development.
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Affiliation(s)
- Jimeng Wu
- Empa, Swiss Federal Laboratories for Materials Science and Technology, Particles-Biology Interactions Laboratory, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland; Empa, Swiss Federal Laboratories for Materials Science and Technology, Technology and Society Laboratory, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland
| | - Govind Gupta
- Empa, Swiss Federal Laboratories for Materials Science and Technology, Particles-Biology Interactions Laboratory, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland
| | - Tina Buerki-Thurnherr
- Empa, Swiss Federal Laboratories for Materials Science and Technology, Particles-Biology Interactions Laboratory, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland
| | - Bernd Nowack
- Empa, Swiss Federal Laboratories for Materials Science and Technology, Technology and Society Laboratory, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland
| | - Peter Wick
- Empa, Swiss Federal Laboratories for Materials Science and Technology, Particles-Biology Interactions Laboratory, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland.
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Younes M, Aquilina G, Castle L, Degen G, Engel K, Fowler P, Frutos Fernandez MJ, Fürst P, Gürtler R, Husøy T, Manco M, Mennes W, Moldeus P, Passamonti S, Shah R, Waalkens‐Berendsen I, Wright M, Andreoli C, Bastos M, Benford D, Bignami M, Bolognesi C, Cheyns K, Corsini E, Crebelli R, Dusemund B, Fitzgerald R, Gaffet E, Loeschner K, Marcon F, Mast J, Mirat M, Mortensen A, Oomen A, Schlatter J, Turck D, Ulbrich B, Undas A, Vleminckx C, Woelfle D, Woutersen R, Barmaz S, Dino B, Gagliardi G, Levorato S, Mazzoli E, Nathanail A, Rincon AM, Ruggeri L, Smeraldi C, Tard A, Vermeiren S, Gundert‐Remy U. Re-evaluation of silicon dioxide (E 551) as a food additive in foods for infants below 16 weeks of age and follow-up of its re-evaluation as a food additive for uses in foods for all population groups. EFSA J 2024; 22:e8880. [PMID: 39421729 PMCID: PMC11483555 DOI: 10.2903/j.efsa.2024.8880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2024] Open
Abstract
The present opinion is the follow-up of the conclusions and recommendations of the Scientific Opinion on the re-evaluation of silicon dioxide (E 551) as a food additive relevant to the safety assessment for all age groups. In addition, the risk assessment of silicon dioxide (E 551) for its use in food for infants below 16 weeks of age is performed. Based on the newly available information on the characterisation of the SAS used as E 551 and following the principles of the 2021 EFSA Guidance on Particle-TR, the conventional safety assessment has been complemented with nano-specific considerations. Given the uncertainties resulting from the limitations of the database and in the absence of genotoxicity concern, the Panel considered that it is not appropriate to derive an acceptable daily intake (ADI) but applied the margin of exposure (MOE) approach for the risk assessment. The Panel concluded that the MOE should be at least 36 for not raising a safety concern. The calculated MOEs considering the dietary exposure estimates for all population groups using the refined non-brand loyal scenario, estimated at the time of the 2018 re-evaluation, were all above 36. The Panel concluded that E 551 does not raise a safety concern in all population groups at the reported uses and use levels. The use of E 551 in food for infants below 16 weeks of age in FC 13.1.1 and FC 13.1.5.1 does not raise a safety concern at the current exposure levels. The Panel also concluded that the technical data provided support an amendment of the specifications for E 551 laid down in Commission Regulation (EU) No 231/2012. The paucity of toxicological studies with proper dispersion protocol (with the exception of the genotoxicity studies) creates uncertainty in the present assessment of the potential toxicological effects related to the exposure to E 551 nanosize aggregates.
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Bianchi MG, Chiu M, Taurino G, Bergamaschi E, Turroni F, Mancabelli L, Longhi G, Ventura M, Bussolati O. Amorphous silica nanoparticles and the human gut microbiota: a relationship with multiple implications. J Nanobiotechnology 2024; 22:45. [PMID: 38291460 PMCID: PMC10826219 DOI: 10.1186/s12951-024-02305-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 01/23/2024] [Indexed: 02/01/2024] Open
Abstract
Amorphous silica nanoparticles (ASNP) are among the nanomaterials that are produced in large quantities. ASNP have been present for a long time in several fast-moving consumer products, several of which imply exposure of the gastrointestinal tract, such as toothpastes, food additives, drug excipients, and carriers. Consolidated use and experimental evidence have consistently pointed to the very low acute toxicity and limited absorption of ASNP. However, slow absorption implies prolonged exposure of the intestinal epithelium to ASNP, with documented effects on intestinal permeability and immune gut homeostasis. These effects could explain the hepatic toxicity observed after oral administration of ASNP in animals. More recently, the role of microbiota in these and other ASNP effects has attracted increasing interest in parallel with the recognition of the role of microbiota in a variety of conditions. Although evidence for nanomaterial effects on microbiota is particularly abundant for materials endowed with bactericidal activities, a growing body of recent experimental data indicates that ASNPs also modify microbiota. The implications of these effects are recounted in this contribution, along with a discussion of the more important open issues and recommendations for future research.
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Affiliation(s)
- Massimiliano G Bianchi
- Lab. of General Pathology, Dept. of Medicine and Surgery, University of Parma, Parma, Italy.
- Interdepartmental Research Centre "Microbiome Research Hub", University of Parma, Parma, Italy.
| | - Martina Chiu
- Lab. of General Pathology, Dept. of Medicine and Surgery, University of Parma, Parma, Italy
| | - Giuseppe Taurino
- Lab. of General Pathology, Dept. of Medicine and Surgery, University of Parma, Parma, Italy
- Interdepartmental Research Centre "Microbiome Research Hub", University of Parma, Parma, Italy
| | - Enrico Bergamaschi
- Department of Public Health Sciences and Paediatrics, University of Turin, Turin, Italy
| | - Francesca Turroni
- Interdepartmental Research Centre "Microbiome Research Hub", University of Parma, Parma, Italy
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parma, Italy
| | - Leonardo Mancabelli
- Interdepartmental Research Centre "Microbiome Research Hub", University of Parma, Parma, Italy
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parma, Italy
| | - Giulia Longhi
- Interdepartmental Research Centre "Microbiome Research Hub", University of Parma, Parma, Italy
| | - Marco Ventura
- Interdepartmental Research Centre "Microbiome Research Hub", University of Parma, Parma, Italy
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parma, Italy
| | - Ovidio Bussolati
- Lab. of General Pathology, Dept. of Medicine and Surgery, University of Parma, Parma, Italy
- Interdepartmental Research Centre "Microbiome Research Hub", University of Parma, Parma, Italy
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Cary C, Stapleton P. Determinants and mechanisms of inorganic nanoparticle translocation across mammalian biological barriers. Arch Toxicol 2023; 97:2111-2131. [PMID: 37303009 PMCID: PMC10540313 DOI: 10.1007/s00204-023-03528-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 05/22/2023] [Indexed: 06/13/2023]
Abstract
Biological barriers protect delicate internal tissues from exposures to and interactions with hazardous materials. Primary anatomical barriers prevent external agents from reaching systemic circulation and include the pulmonary, gastrointestinal, and dermal barriers. Secondary barriers include the blood-brain, blood-testis, and placental barriers. The tissues protected by secondary barriers are particularly sensitive to agents in systemic circulation. Neurons of the brain cannot regenerate and therefore must have limited interaction with cytotoxic agents. In the testis, the delicate process of spermatogenesis requires a specific milieu distinct from the blood. The placenta protects the developing fetus from compounds in the maternal circulation that would impair limb or organ development. Many biological barriers are semi-permeable, allowing only materials or chemicals, with a specific set of properties, that easily pass through or between cells. Nanoparticles (particles less than 100 nm) have recently drawn specific concern due to the possibility of biological barrier translocation and contact with distal tissues. Current evidence suggests that nanoparticles translocate across both primary and secondary barriers. It is known that the physicochemical properties of nanoparticles can affect biological interactions, and it has been shown that nanoparticles can breach primary and some secondary barriers. However, the mechanism by which nanoparticles cross biological barriers has yet to be determined. Therefore, the purpose of this review is to summarize how different nanoparticle physicochemical properties interact with biological barriers and barrier products to govern translocation.
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Affiliation(s)
- Chelsea Cary
- Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ, 08854, USA
| | - Phoebe Stapleton
- Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Environmental and Occupational Health Sciences Institute, Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ, 08854, USA.
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Rolo D, Assunção R, Ventura C, Alvito P, Gonçalves L, Martins C, Bettencourt A, Jordan P, Vital N, Pereira J, Pinto F, Matos P, Silva MJ, Louro H. Adverse Outcome Pathways Associated with the Ingestion of Titanium Dioxide Nanoparticles-A Systematic Review. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:nano12193275. [PMID: 36234403 PMCID: PMC9565478 DOI: 10.3390/nano12193275] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/12/2022] [Accepted: 09/13/2022] [Indexed: 05/15/2023]
Abstract
Titanium dioxide nanoparticles (TiO2-NPs) are widely used, and humans are exposed through food (E171), cosmetics (e.g., toothpaste), and pharmaceuticals. The oral and gastrointestinal (GIT) tract are the first contact sites, but it may be systemically distributed. However, a robust adverse outcome pathway (AOP) has not been developed upon GIT exposure to TiO2-NPs. The aim of this review was to provide an integrative analysis of the published data on cellular and molecular mechanisms triggered after the ingestion of TiO2-NPs, proposing plausible AOPs that may drive policy decisions. A systematic review according to Prisma Methodology was performed in three databases of peer-reviewed literature: Pubmed, Scopus, and Web of Science. A total of 787 records were identified, screened in title/abstract, being 185 used for data extraction. The main endpoints identified were oxidative stress, cytotoxicity/apoptosis/cell death, inflammation, cellular and systemic uptake, genotoxicity, and carcinogenicity. From the results, AOPs were proposed where colorectal cancer, liver injury, reproductive toxicity, cardiac and kidney damage, as well as hematological effects stand out as possible adverse outcomes. The recent transgenerational studies also point to concerns with regard to population effects. Overall, the findings further support a limitation of the use of TiO2-NPs in food, announced by the European Food Safety Authority (EFSA).
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Affiliation(s)
- Dora Rolo
- National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- ToxOmics—Centre for Toxicogenomics and Human Health, NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
- Correspondence:
| | - Ricardo Assunção
- National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- CESAM, Centre for Environmental and Marine Studies, University of Aveiro, 3810-193 Aveiro, Portugal
- IUEM, Instituto Universitário Egas Moniz, Egas Moniz-Cooperativa de Ensino Superior, CRL, 2829-511 Monte de Caparica, Portugal
| | - Célia Ventura
- National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- ToxOmics—Centre for Toxicogenomics and Human Health, NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
| | - Paula Alvito
- National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- CESAM, Centre for Environmental and Marine Studies, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Lídia Gonçalves
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, 1649-003 Lisbon, Portugal
| | - Carla Martins
- National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- NOVA National School of Public Health, Public Health Research Centre, Universidade NOVA de Lisboa, 1600-560 Lisbon, Portugal
- Comprehensive Health Research Center (CHRC), 1169-056 Lisbon, Portugal
| | - Ana Bettencourt
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, 1649-003 Lisbon, Portugal
| | - Peter Jordan
- National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- BioISI—Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal
| | - Nádia Vital
- National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- ToxOmics—Centre for Toxicogenomics and Human Health, NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
- NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
| | - Joana Pereira
- National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- BioISI—Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal
| | - Fátima Pinto
- National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- ToxOmics—Centre for Toxicogenomics and Human Health, NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
| | - Paulo Matos
- National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- BioISI—Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal
| | - Maria João Silva
- National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- ToxOmics—Centre for Toxicogenomics and Human Health, NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
| | - Henriqueta Louro
- National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- ToxOmics—Centre for Toxicogenomics and Human Health, NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
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Baranowska-Wójcik E, Szwajgier D, Winiarska-Mieczan A. A review of research on the impact of E171/TiO 2 NPs on the digestive tract. J Trace Elem Med Biol 2022; 72:126988. [PMID: 35561571 DOI: 10.1016/j.jtemb.2022.126988] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 04/01/2022] [Accepted: 04/25/2022] [Indexed: 12/24/2022]
Abstract
Nanotechnology utilises particles of between 1 and 100 nm in size. In recent years, it has enjoyed widespread application in a variety of areas. However, this has also raised increasing concerns regarding the effects that the use of nanoparticles may have on human health. The nanoparticles of titanium dioxide (TiO2 NPs) are among the most promising nanomaterials and have already found wide use in cosmetics, medicine and, the food industry. A nano-sized (diameter < 100 nm) fraction of TiO2 is present, at a certain percentage, in the E171 ( in the EU) pigment commonly used as an additive in food, whose presence raises particular concerns in terms of its potential negative health impact. The consumption of E171 food additive is increasingly associated with disorders of the intestinal barrier, including intestinal dysbiosis. It may disrupt the normal functions of the gastrointestinal tract (GIT) including: enzymatic digestion of primary nutrients (lipids, proteins, or carbohydrates). The aim of this review is to provide a comprehensive and reliable overview of studies conducted in recent years in terms of the substance's potentially negative impact on human and animal alimentary systems.
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Affiliation(s)
- Ewa Baranowska-Wójcik
- Department of Biotechnology, Microbiology and Human Nutrition, University of Life Sciences in Lublin, Skromna 8, Lublin 20-704, Poland.
| | - Dominik Szwajgier
- Department of Biotechnology, Microbiology and Human Nutrition, University of Life Sciences in Lublin, Skromna 8, Lublin 20-704, Poland
| | - Anna Winiarska-Mieczan
- Institute of Animal Nutrition and Bromatology, Department of Bromatology and Food Physiology, University of Life Sciences in Lublin, Akademicka 13, Lublin 20-950, Poland
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Mittag A, Singer A, Hoera C, Westermann M, Kämpfe A, Glei M. Impact of in vitro digested zinc oxide nanoparticles on intestinal model systems. Part Fibre Toxicol 2022; 19:39. [PMID: 35644618 PMCID: PMC9150335 DOI: 10.1186/s12989-022-00479-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 05/23/2022] [Indexed: 11/13/2022] Open
Abstract
Background Zinc oxide nanoparticles (ZnO NP) offer beneficial properties for many applications, especially in the food sector. Consequently, as part of the human food chain, they are taken up orally. The toxicological evaluation of orally ingested ZnO NP is still controversial. In addition, their physicochemical properties can change during digestion, which leads to an altered biological behaviour. Therefore, the aim of our study was to investigate the fate of two different sized ZnO NP (< 50 nm and < 100 nm) during in vitro digestion and their effects on model systems of the intestinal barrier. Differentiated Caco-2 cells were used in mono- and coculture with mucus-producing HT29-MTX cells. The cellular uptake, the impact on the monolayer barrier integrity and cytotoxic effects were investigated after 24 h exposure to 123–614 µM ZnO NP. Results
In vitro digested ZnO NP went through a morphological and chemical transformation with about 70% free zinc ions after the intestinal phase. The cellular zinc content increased dose-dependently up to threefold in the monoculture and fourfold in the coculture after treatment with digested ZnO NP. This led to reactive oxygen species but showed no impact on cellular organelles, the metabolic activity, and the mitochondrial membrane potential. Only very small amounts of zinc (< 0.7%) reached the basolateral area, which is due to the unmodified transepithelial electrical resistance, permeability, and cytoskeletal morphology. Conclusions Our results reveal that digested and, therefore, modified ZnO NP interact with cells of an intact intestinal barrier. But this is not associated with serious cell damage.
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Baumgartner J, Winkler HC, Zandberg L, Tuntipopipat S, Mankong P, Bester C, Hilty F, Zeevaart JR, Gowachirapant S, Zimmermann MB. Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women. Sci Rep 2022; 12:2792. [PMID: 35181698 PMCID: PMC8857185 DOI: 10.1038/s41598-022-06701-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 01/20/2022] [Indexed: 11/09/2022] Open
Abstract
Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO4-NP; specific surface area [SSA] 98 m2g-1) compared to to ferrous sulfate (FeSO4), the reference compound. We show that absorption of iron from FePO4-NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO4, without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two 57Fe-labeled FePO4-NP with SSAs of 98 m2g−1 and 188 m2g−1 was 2.8-fold and 5.4-fold higher than from bulk FePO4 with an SSA of 25 m2g−1 (P < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO4-NP 188 m2g-1 achieved 72% relative bioavailability compared to FeSO4. These data suggest FePO4-NPs may be useful for nutritional applications.
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Affiliation(s)
- Jeannine Baumgartner
- Laboratory of Human Nutrition, Department of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 7, 8092, Zurich, Switzerland.,Center of Excellence in Nutrition, North-West University, Potchefstroom, South Africa
| | - Hans Christian Winkler
- Laboratory of Human Nutrition, Department of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 7, 8092, Zurich, Switzerland
| | - Lizelle Zandberg
- Center of Excellence in Nutrition, North-West University, Potchefstroom, South Africa
| | | | - Phatchari Mankong
- Institute of Nutrition, Mahidol University, Salaya, Nakhon Pathom, 73170, Thailand
| | - Cor Bester
- DST/NWU Preclinical Drug Development Platform, North-West University, Potchefstroom, South Africa
| | - Florentine Hilty
- Laboratory of Human Nutrition, Department of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 7, 8092, Zurich, Switzerland
| | - Jan Rijn Zeevaart
- DST/NWU Preclinical Drug Development Platform, North-West University, Potchefstroom, South Africa.,South African Nuclear Energy Corporation South Africa (Necsa), Pelindaba, South Africa
| | | | - Michael B Zimmermann
- Laboratory of Human Nutrition, Department of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 7, 8092, Zurich, Switzerland.
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Food Additives, a Key Environmental Factor in the Development of IBD through Gut Dysbiosis. Microorganisms 2022; 10:microorganisms10010167. [PMID: 35056616 PMCID: PMC8780106 DOI: 10.3390/microorganisms10010167] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/04/2022] [Accepted: 01/11/2022] [Indexed: 12/12/2022] Open
Abstract
Diet is a key environmental factor in inflammatory bowel disease (IBD) and, at the same time, represents one of the most promising therapies for IBD. Our daily diet often contains food additives present in numerous processed foods and even in dietary supplements. Recently, researchers and national authorities have been paying much attention to their toxicity and effects on gut microbiota and health. This review aims to gather the latest data focusing on the potential role of food additives in the pathogenesis of IBDs through gut microbiota modulation. Some artificial emulsifiers and sweeteners can induce the dysbiosis associated with an alteration of the intestinal barrier, an activation of chronic inflammation, and abnormal immune response accelerating the onset of IBD. Even if most of these results are retrieved from in vivo and in vitro studies, many artificial food additives can represent a potential hidden driver of gut chronic inflammation through gut microbiota alterations, especially in a population with IBD predisposition. In this context, pending the confirmation of these results by large human studies, it would be advisable that IBD patients avoid the consumption of processed food containing artificial food additives and follow a personalized nutritional therapy prescribed by a clinical nutritionist.
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Vieira A, Gramacho A, Rolo D, Vital N, Silva MJ, Louro H. Cellular and Molecular Mechanisms of Toxicity of Ingested Titanium Dioxide Nanomaterials. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1357:225-257. [DOI: 10.1007/978-3-030-88071-2_10] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AbstractAn exponential increase in products containing titanium dioxide nanomaterials (TiO2), in agriculture, food and feed industry, lead to increased oral exposure to these nanomaterials (NMs). Thus, the gastrointestinal tract (GIT) emerges as a possible route of exposure that may drive systemic exposure, if the intestinal barrier is surpassed. NMs have been suggested to produce adverse outcomes, such as genotoxic effects, that are associated with increased risk of cancer, leading to a concern for public health. However, to date, the differences in the physicochemical characteristics of the NMs studied and other variables in the test systems have generated contradictory results in the literature. Processes like human digestion may change the NMs characteristics, inducing unexpected toxic effects in the intestine. Using TiO2 as case-study, this chapter provides a review of the works addressing the interactions of NMs with biological systems in the context of intestinal tract and digestion processes, at cellular and molecular level. The knowledge gaps identified suggest that the incorporation of a simulated digestion process for in vitro studies has the potential to improve the model for elucidating key events elicited by these NMs, advancing the nanosafety studies towards the development of an adverse outcome pathway for intestinal effects.
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Lu N, Chen Z, Song J, Weng Y, Yang G, Liu Q, Yang K, Lu X, Liu Y. Size Effect of TiO2 Nanoparticles as Food Additive and Potential Toxicity. FOOD BIOPHYS 2021. [DOI: 10.1007/s11483-021-09695-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Tsymbalyuk OV, Davydovska TL, Naumenko AM, Liashevych AN, Lupaina IS, Voiteshenko IS, Nuryshchenko NY, Skryshevsky VA. Functional state of the myometrium of rats under chronic in vivo effect of nanostructured ZnO and ТіО2 materials. REGULATORY MECHANISMS IN BIOSYSTEMS 2021. [DOI: 10.15421/022179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
The specificities of the structure and blood supply of the uterus facilitate a considerable accumulation of nanosized xenobiotics, including nanoparticles of metal oxides, in its tissues. Numerous in vitro and in vivo experiments demonstrated that nanoparticles of metal oxides (ZnO and TiO2) have significant cytotoxic activity, caused by oxidative stress induction. However, there is no information about the impact of these nanomaterials on the functional state of the myometrium under chronic exposure on the organism. Tenzometric methods and mechanokinetic analysis were used in our work to investigate the contractile activity of the myometrium of non-pregnant rats. The contractile activity was either spontaneous or induced by oxytocin (the uterotonic hormone) and acetylcholine (the agonist of muscarinic choline receptors) under chronic peroral intake of the ZnO and TiO2 aqueous nanocolloids into the organism. It was found that after burdening of rats with ZnO and ТіО2 aqueous nanocolloids there were no changes in the pacemaker-dependent mechanisms forming the frequency of spontaneous contractions in the myometrium, but there was a considerably induced increase in the AU index of contractions. It was shown that during the oxytocin-induced excitation of the myometrium under both chronic and short-term burdening of the rats with ZnO and TiO2 aqueous nanocolloids, the mechanisms that regulate the intracellular concentration of Ca2+ ions are the target for the nanomaterials. When the rats were burdened with ZnO aqueous nanocolloids for 6 months, during cholinergic excitation there was hyperstimulation of both M3-receptor-dependent mechanisms of Са2+ ions intake via the potential-governed Са2+-channels of L-type into the smooth muscles of the myometrium, and M2-receptor-dependent mechanisms, controlling the intracellular concentration of these cations. Thus, the regularities and mechanisms of the change in the functioning of uterine smooth muscles under chronic intake of the ZnO and TiO2 aqueous nanocolloids were determined in this study.
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Behaviour of Titanium Dioxide Particles in Artificial Body Fluids and Human Blood Plasma. Int J Mol Sci 2021; 22:ijms221910614. [PMID: 34638952 PMCID: PMC8509028 DOI: 10.3390/ijms221910614] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 09/22/2021] [Accepted: 09/24/2021] [Indexed: 12/13/2022] Open
Abstract
The growing application of materials containing TiO2 particles has led to an increased risk of human exposure, while a gap in knowledge about the possible adverse effects of TiO2 still exists. In this work, TiO2 particles of rutile, anatase, and their commercial mixture were exposed to various environments, including simulated gastric fluids and human blood plasma (both representing in vivo conditions), and media used in in vitro experiments. Simulated body fluids of different compositions, ionic strengths, and pH were used, and the impact of the absence or presence of chosen enzymes was investigated. The physicochemical properties and agglomeration of TiO2 in these media were determined. The time dependent agglomeration of TiO2 related to the type of TiO2, and mainly to the type and composition of the environment that was observed. The presence of enzymes either prevented or promoted TiO2 agglomeration. TiO2 was also observed to exhibit concentration-dependent cytotoxicity. This knowledge about TiO2 behavior in all the abovementioned environments is critical when TiO2 safety is considered, especially with respect to the significant impact of the presence of proteins and size-related cytotoxicity.
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Deng J, Ding QM, Jia MX, Li W, Zuberi Z, Wang JH, Ren JL, Fu D, Zeng XX, Luo JF. Biosafety risk assessment of nanoparticles: Evidence from food case studies. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2021; 275:116662. [PMID: 33582638 DOI: 10.1016/j.envpol.2021.116662] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 12/21/2020] [Accepted: 02/02/2021] [Indexed: 05/04/2023]
Abstract
Nanotechnology provides a wide range of benefits in the food industry in improving food tastes, textures, sensations, quality, shelf life, and food safety. Recently, potential adverse effects such as toxicity and safety concerns have been associated with the increasing use of engineered nanoparticles in food industry. Additionally, very limited information is known concerning the behavior, properties and effects of food nano-materials in the gastrointestinal tract. There is explores the current advances and provides insights of the potential risks of nanoparticles in the food industry. Specifically, characteristics of food nanoparticles and their absorption in the gastrointestinal tract, the effects of food nanoparticles against the gastrointestinal microflora, and the potential toxicity mechanisms in different organs and body systems are discussed. This review would provide references for further investigation of nano-materials toxicity effect in foods and their molecular mechanisms. It will help to develop safer foods and expand nano-materials applications in safe manner.
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Affiliation(s)
- Jing Deng
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible Forestry Resources Safety and Processing Utilization, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China; College of Packaging and Material Engineering, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou, 412007, China
| | - Quan Ming Ding
- College of Packaging and Material Engineering, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou, 412007, China
| | - Ming Xi Jia
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible Forestry Resources Safety and Processing Utilization, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China
| | - Wen Li
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible Forestry Resources Safety and Processing Utilization, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China; College of Packaging and Material Engineering, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou, 412007, China.
| | - Zavuga Zuberi
- Department of Science and Laboratory Technology, Dar Es Salaam Institute of Technology, P.O. Box 2958, Dar Es Salaam, Tanzania
| | - Jian Hui Wang
- School of Chemistry and Food Engineering, Changsha University of Science and Technology, Changsha, Hunan, 410114, China
| | - Jia Li Ren
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible Forestry Resources Safety and Processing Utilization, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China
| | - Da Fu
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Xiao Xi Zeng
- College of Packaging and Material Engineering, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou, 412007, China
| | - Jun Fei Luo
- National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible Forestry Resources Safety and Processing Utilization, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China
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Dudefoi W, Rabesona H, Rivard C, Mercier-Bonin M, Humbert B, Terrisse H, Ropers MH. In vitro digestion of food grade TiO 2 (E171) and TiO 2 nanoparticles: physicochemical characterization and impact on the activity of digestive enzymes. Food Funct 2021; 12:5975-5988. [PMID: 34032251 DOI: 10.1039/d1fo00499a] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Titanium dioxide is a food additive that has raised some concerns for humans due to the presence of nanoparticles. We were interested in knowing the fate of TiO2 particles in the gastro-intestinal tract and their potential effect on digestive enzymes. For this purpose, we analysed the behaviour of two different food grade TiO2 samples (E171) and one nano-sized TiO2 sample (P25) through a standardized static in vitro digestion protocol simulating the oral, gastric and intestinal phases with appropriate juices including enzymes. Both E171 and P25 TiO2 particles remained intact in the digestive fluids but formed large agglomerates, and especially in the intestinal fluid where up to 500 μm sized particles have been identified. The formation of these agglomerates is mediated by the adsorption of mainly α-amylase and divalent cations. Pepsin was also identified to adsorb onto TiO2 particles but only in the case of silica-covered E171. In the salivary conditions, TiO2 exerted an inhibitory action on the enzymatic activity of α-amylase. The activity was reduced by a factor dependent on enzyme concentrations (up to 34% at 1 mg mL-1) but this inhibitory effect was reduced to hardly 10% in the intestinal fluid. In the gastric phase, pepsin was not affected by any form of TiO2. Our results hint that food grade TiO2 has a limited impact on the global digestion of carbohydrates and proteins. However, the reduced activity specifically observed in the oral phase deserves deeper investigation to prevent any adverse health effects related to the slowdown of carbohydrate metabolism.
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Affiliation(s)
- William Dudefoi
- INRAE, UR1268 Biopolymères Interactions Assemblages, 44300 Nantes, France.
| | - Hanitra Rabesona
- INRAE, UR1268 Biopolymères Interactions Assemblages, 44300 Nantes, France.
| | - Camille Rivard
- INRAE, UAR 1008 TRANSFORM, 44300 Nantes, France and Synchrotron SOLEIL, LUCIA Beamline, 91192 Gif-sur-Yvette, France
| | - Muriel Mercier-Bonin
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Bernard Humbert
- Université de Nantes, CNRS, Institut des Matériaux Jean Rouxel, IMN, F-44000 Nantes, France
| | - Hélène Terrisse
- Université de Nantes, CNRS, Institut des Matériaux Jean Rouxel, IMN, F-44000 Nantes, France
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Interaction of food-grade titanium dioxide nanoparticles with pepsin in simulated gastric fluid. Lebensm Wiss Technol 2020. [DOI: 10.1016/j.lwt.2020.110208] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Skočaj M, Bizjak M, Strojan K, Lojk J, Erdani Kreft M, Miš K, Pirkmajer S, Bregar VB, Veranič P, Pavlin M. Proposing Urothelial and Muscle In Vitro Cell Models as a Novel Approach for Assessment of Long-Term Toxicity of Nanoparticles. Int J Mol Sci 2020; 21:ijms21207545. [PMID: 33066271 PMCID: PMC7589566 DOI: 10.3390/ijms21207545] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 10/07/2020] [Accepted: 10/09/2020] [Indexed: 12/11/2022] Open
Abstract
Many studies evaluated the short-term in vitro toxicity of nanoparticles (NPs); however, long-term effects are still not adequately understood. Here, we investigated the potential toxic effects of biomedical (polyacrylic acid and polyethylenimine coated magnetic NPs) and two industrial (SiO2 and TiO2) NPs following different short-term and long-term exposure protocols on two physiologically different in vitro models that are able to differentiate: L6 rat skeletal muscle cell line and biomimetic normal porcine urothelial (NPU) cells. We show that L6 cells are more sensitive to NP exposure then NPU cells. Transmission electron microscopy revealed an uptake of NPs into L6 cells but not NPU cells. In L6 cells, we obtained a dose-dependent reduction in cell viability and increased reactive oxygen species (ROS) formation after 24 h. Following continuous exposure, more stable TiO2 and polyacrylic acid (PAA) NPs increased levels of nuclear factor Nrf2 mRNA, suggesting an oxidative damage-associated response. Furthermore, internalized magnetic PAA and TiO2 NPs hindered the differentiation of L6 cells. We propose the use of L6 skeletal muscle cells and NPU cells as a novel approach for assessment of the potential long-term toxicity of relevant NPs that are found in the blood and/or can be secreted into the urine.
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Affiliation(s)
- Matej Skočaj
- Group for nano and biotechnological applications, Faculty of Electrical Engineering, University of Ljubljana, SI-1000 Ljubljana, Slovenia; (M.S.); (M.B.); (K.S.); (J.L.); (V.B.B.)
- Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia; (K.M.); (S.P.)
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia;
| | - Maruša Bizjak
- Group for nano and biotechnological applications, Faculty of Electrical Engineering, University of Ljubljana, SI-1000 Ljubljana, Slovenia; (M.S.); (M.B.); (K.S.); (J.L.); (V.B.B.)
- Institute of Biophysics, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia
| | - Klemen Strojan
- Group for nano and biotechnological applications, Faculty of Electrical Engineering, University of Ljubljana, SI-1000 Ljubljana, Slovenia; (M.S.); (M.B.); (K.S.); (J.L.); (V.B.B.)
| | - Jasna Lojk
- Group for nano and biotechnological applications, Faculty of Electrical Engineering, University of Ljubljana, SI-1000 Ljubljana, Slovenia; (M.S.); (M.B.); (K.S.); (J.L.); (V.B.B.)
- Institute of Biophysics, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia
| | - Mateja Erdani Kreft
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia;
| | - Katarina Miš
- Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia; (K.M.); (S.P.)
| | - Sergej Pirkmajer
- Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia; (K.M.); (S.P.)
| | - Vladimir Boštjan Bregar
- Group for nano and biotechnological applications, Faculty of Electrical Engineering, University of Ljubljana, SI-1000 Ljubljana, Slovenia; (M.S.); (M.B.); (K.S.); (J.L.); (V.B.B.)
| | - Peter Veranič
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia;
- Correspondence: (P.V.); (M.P.)
| | - Mojca Pavlin
- Group for nano and biotechnological applications, Faculty of Electrical Engineering, University of Ljubljana, SI-1000 Ljubljana, Slovenia; (M.S.); (M.B.); (K.S.); (J.L.); (V.B.B.)
- Institute of Biophysics, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia
- Correspondence: (P.V.); (M.P.)
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Setyawati MI, Zhao Z, Ng KW. Transformation of Nanomaterials and Its Implications in Gut Nanotoxicology. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2020; 16:e2001246. [PMID: 32495486 DOI: 10.1002/smll.202001246] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 04/24/2020] [Indexed: 06/11/2023]
Abstract
Ingestion of engineered nanomaterials (ENMs) is inevitable due to their widespread utilization in the agrifood industry. Safety evaluation has become pivotal to identify the consequences on human health of exposure to these ingested ENMs. Much of the current understanding of nanotoxicology in the gastrointestinal tract (GIT) is derived from studies utilizing pristine ENMs. In reality, agrifood ENMs interact with their microenvironment, and undergo multiple physicochemical transformations, such as aggregation/agglomeration, dissolution, speciation change, and surface characteristics alteration, across their life cycle from synthesis to consumption. This work sieves out the implications of ENM transformations on their behavior, stability, and reactivity in food and product matrices and through the GIT, in relation to measured toxicological profiles. In particular, a strong emphasis is given to understand the mechanisms through which these transformations can affect ENM induced gut nanotoxicity.
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Affiliation(s)
- Magdiel Inggrid Setyawati
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore
| | - Zhitong Zhao
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore
| | - Kee Woei Ng
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore
- Department of Environmental Health, Harvard T. H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA
- Environmental Chemistry and Materials Centre, Nanyang Environment and Water Research Institute (NEWRI), Nanyang Technological University, 1 Cleantech Loop, CleanTech One, Singapore, 637141, Singapore
- Skin Research Institute of Singapore, Biomedical Science Institutes, Immunos, 8A Biomedical Grove, Singapore, 138648, Singapore
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21
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Mosa IF, Abd HH, Abuzreda A, Assaf N, Yousif AB. Bio-evaluation of the role of chitosan and curcumin nanoparticles in ameliorating genotoxicity and inflammatory responses in rats' gastric tissue followed hydroxyapatite nanoparticles' oral uptake. Toxicol Res (Camb) 2020; 9:493-508. [PMID: 32905138 DOI: 10.1093/toxres/tfaa054] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 05/26/2020] [Accepted: 06/30/2020] [Indexed: 11/14/2022] Open
Abstract
Hydroxyapatite has been extensively used in tissue engineering due to its osteogenic potency, but its present toxicological facts are relatively insufficient. Here, the possible gastric toxicity of hydroxyapatite nanoparticles was evaluated biochemically to determine oxidant and antioxidant parameters in rats' stomach tissues. At results, hydroxyapatite nanoparticles have declined stomach antioxidant enzymes and reduced glutathione level, while an induction in lipid peroxidation and nitric oxide has been observed. Furthermore, DNA oxidation was analyzed by the suppression of toll-like receptors 2, nuclear factor-kappa B and Forkhead box P3 gene expression and also 8-Oxo-2'-deoxyguanosine level as a genotoxicity indicator. Various pro-inflammatory gene products have been identified that intercede a vital role in proliferation and apoptosis suppression, among these products: tumor suppressor p53, tumor necrosis factor-α and interliukin-6. Moreover, the hydroxyapatite-treated group revealed wide histological alterations and significant elevation in the number of proliferating cell nuclear antigen-positive cells, which has been observed in the mucosal layer of the small intestine, and these alterations are an indication of small intestine injury, while the appearance of chitosan and curcumin nanoparticles in the combination group showed improvement in all the above parameters with inhibition of toxic-oxidant parameters and activation of antioxidant parameters.
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Affiliation(s)
- Israa F Mosa
- Department of Biological Science and Animal Physiology, Institute of Graduate Studies and Research, Alexandria University, Egypt
| | - Haitham H Abd
- Department of Biological Science and Animal Physiology, Institute of Graduate Studies and Research, Alexandria University, Egypt
| | - Abdelsalam Abuzreda
- Department of Health, Safety and Environment (HSE), Arabian Gulf Oil Company (AGOCO), Benghazi, Libya
| | - Nadhom Assaf
- Department of Biological Science and Animal Physiology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt
| | - Amenh B Yousif
- Department of Family and Community Medicine, Faculty of Medicine, University of Benghazi, Benghazi, Libya
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Analysis of the Characteristics and Cytotoxicity of Titanium Dioxide Nanomaterials Following Simulated In Vitro Digestion. NANOMATERIALS 2020; 10:nano10081516. [PMID: 32748892 PMCID: PMC7466536 DOI: 10.3390/nano10081516] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/27/2020] [Accepted: 07/30/2020] [Indexed: 12/15/2022]
Abstract
Several metallic nanomaterials (NMs), such as titanium dioxide nanomaterials (TiO2), present beneficial properties with a broad range of innovative applications. The human population is exposed to TiO2, particularly by ingestion, due to its increasing use as a food additive and inclusion in dietary supplements and food packaging materials. Whether this oral exposure may lead to adverse local or systemic outcomes has been the subject of research, but studies have generated contradictory results, reflecting differences in the physicochemical properties of the TiO2 studied, effects of the surrounding matrix, and modifications during digestion. This work aimed to investigate the toxic effects of three different TiO2 NMs (NM-103, NM-103 and NM-105) on the gastrointestinal tract cells, Caco-2 and HT29-MTX-E12, after the use of the standardized static INFOGEST 2.0 in vitro digestion method to mimic human digestion of TiO2, contributing to hazard assessment. The results show that, for one of the digested TiO2 NMs studied (NM-105), a more pronounced toxicity occurs after exposure of HT29-MTX-E12 intestinal cells, as compared to undigested NM, concomitantly with subtle changes in characteristics of the NM. Thus, the inclusion of the digestion simulation in the safety evaluation of ingested NMs through in vitro bioassays can better integrate the modifications that NMs suffer in the organism. It is expected that such an approach will reduce uncertainties in the hazard assessment of ingested NMs for human health.
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Rogers KR, Henson TE, Navratilova J, Surette M, Hughes MF, Bradham KD, Stefaniak AB, Knepp AK, Bowers L. In vitro intestinal toxicity of commercially available spray disinfectant products advertised to contain colloidal silver. THE SCIENCE OF THE TOTAL ENVIRONMENT 2020; 728:138611. [PMID: 32344222 PMCID: PMC7786200 DOI: 10.1016/j.scitotenv.2020.138611] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 04/08/2020] [Accepted: 04/08/2020] [Indexed: 05/22/2023]
Abstract
The use of colloidal silver-containing products as dietary supplements, immune boosters and surface disinfectants has increased in recent years which has elevated the potential for human exposure to silver nanoparticles and ions. Product mislabeling and long-term use of these products may put consumers at risk for adverse health outcomes including argyria. This study assessed several physical and chemical characteristics of five commercial products as well as their cytotoxicity using a rat intestinal epithelial cell (IEC-6) model. Concentrations of silver were determined for both the soluble and particulate fractions of the products. Primary particle size distribution and elemental composition were determined by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. Hydrodynamic diameters were measured using nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS). The effect of gastrointestinal (GI) simulation on the colloidal silver products was determined using two systems. First, physical and chemical changes of the silver nanoparticles in these products was assessed after exposure to Synthetic Stomach Fluid (SSF) resulting in particle agglomeration, and the appearance of AgCl on the surfaces and between particles. IEC-6 cells were exposed for 24 h to dilutions of the products and assessed for cell viability. The products were also treated with a three-stage simulated GI system (stomach and intestinal fluids) prior to exposure of the IEC-6 cells to the isolated silver nanoparticles. Cell viability was affected by each of the consumer products. Based on the silver nitrate and commercial silver nanoparticle dose response, the cytotoxicity for each of the colloidal silver products was attributed to the particulate silver, soluble silver or non‑silver matrix constituents.
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Affiliation(s)
- Kim R Rogers
- Watershed and Ecosystem Characterization Division, Center for Environmental Measurement and Modeling, Office of Research and Development, USEPA, RTP, NC 27711, United States.
| | - Taylor E Henson
- Oak Ridge Institute for Science and Education, Research Triangle Park, NC 27711, United States; Chemical Characterization and Exposure Division, Center for Computational Toxicology and Exposure, Office of Research and Development, USEPA, RTP, NC 27711, United States
| | - Jana Navratilova
- Watershed and Ecosystem Characterization Division, Center for Environmental Measurement and Modeling, Office of Research and Development, USEPA, RTP, NC 27711, United States
| | - Mark Surette
- Watershed and Ecosystem Characterization Division, Center for Environmental Measurement and Modeling, Office of Research and Development, USEPA, RTP, NC 27711, United States
| | - Michael F Hughes
- Chemical Characterization and Exposure Division, Center for Computational Toxicology and Exposure, Office of Research and Development, USEPA, RTP, NC 27711, United States
| | - Karen D Bradham
- Watershed and Ecosystem Characterization Division, Center for Environmental Measurement and Modeling, Office of Research and Development, USEPA, RTP, NC 27711, United States
| | - Aleksandr B Stefaniak
- National Institute for Occupational Safety and Health, Morgantown, WV 26506, United States
| | - Alycia K Knepp
- National Institute for Occupational Safety and Health, Morgantown, WV 26506, United States
| | - Lauren Bowers
- National Institute for Occupational Safety and Health, Morgantown, WV 26506, United States
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Astrocytes Are More Vulnerable than Neurons to Silicon Dioxide Nanoparticle Toxicity in Vitro. TOXICS 2020; 8:toxics8030051. [PMID: 32751182 PMCID: PMC7560395 DOI: 10.3390/toxics8030051] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/24/2020] [Accepted: 07/25/2020] [Indexed: 11/29/2022]
Abstract
Some studies have shown that silicon dioxide nanoparticles (SiO2-NPs) can reach different regions of the brain and cause toxicity; however, the consequences of SiO2-NPs exposure on the diverse brain cell lineages is limited. We aimed to investigate the neurotoxic effects of SiO2-NP (0–100 µg/mL) on rat astrocyte-rich cultures or neuron-rich cultures using scanning electron microscopy, Attenuated Total Reflection-Fourier Transform Infrared spectroscopy (ATR-FTIR), FTIR microspectroscopy mapping (IQ mapping), and cell viability tests. SiO2-NPs were amorphous particles and aggregated in saline and culture media. Both astrocytes and neurons treated with SiO2-NPs showed alterations in cell morphology and changes in the IR spectral regions corresponding to nucleic acids, proteins, and lipids. The analysis by the second derivative revealed a significant decrease in the signal of the amide I (α-helix, parallel β-strand, and random coil) at the concentration of 10 µg/mL in astrocytes but not in neurons. IQ mapping confirmed changes in nucleic acids, proteins, and lipids in astrocytes; cell death was higher in astrocytes than in neurons (10–100 µg/mL). We conclude that astrocytes were more vulnerable than neurons to SiO2-NPs toxicity. Therefore, the evaluation of human exposure to SiO2-NPs and possible neurotoxic effects must be followed up.
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Chaudhary RG, Bhusari GS, Tiple AD, Rai AR, Somkuvar SR, Potbhare AK, Lambat TL, Ingle PP, Abdala AA. Metal/Metal Oxide Nanoparticles: Toxicity, Applications, and Future Prospects. Curr Pharm Des 2020; 25:4013-4029. [PMID: 31713480 DOI: 10.2174/1381612825666191111091326] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 10/22/2019] [Indexed: 12/12/2022]
Abstract
The ever-growing resistance of pathogens to antibiotics and crop disease due to pest has triggered severe health concerns in recent years. Consequently, there is a need of powerful and protective materials for the eradication of diseases. Metal/metal oxide nanoparticles (M/MO NPs) are powerful agents due to their therapeutic effects in microbial infections. In this context, the present review article discusses the toxicity, fate, effects and applications of M/MO NPs. This review starts with an introduction, followed by toxicity aspects, antibacterial and testing methods and mechanism. In addition, discussion on the impact of different M/MO NPs and their characteristics such as size, shape, particle dissolution on their induced toxicity on food and plants, as well as applications in pesticides. Finally, prospective on current and future issues are presented.
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Affiliation(s)
- Ratiram G Chaudhary
- Post Graduate Department of Chemistry, Seth Kesarimal Porwal College of Arts, Commerce and Science, Kamptee, (Maharashtra)- 441001, India
| | - Ganesh S Bhusari
- Research and Development Division, Apple Chemie India Private Limited, Nagpur-441108, (Maharashtra), India
| | - Ashish D Tiple
- Department of Zoology, Vidyabharti College, Seloo, Wardha (Maharashtra), India
| | - Alok R Rai
- Post Graduate Department of Microbiology, Seth Kesarimal Porwal College of Arts, Commerce and Science, Kamptee, (Maharashtra)-441001, India
| | - Subhash R Somkuvar
- Department of Botany, Dr. Ambedkar College, Nagpur, (Maharashtra)-440 010, India
| | - Ajay K Potbhare
- Post Graduate Department of Chemistry, Seth Kesarimal Porwal College of Arts, Commerce and Science, Kamptee, (Maharashtra)- 441001, India
| | - Trimurti L Lambat
- Department of Chemistry, Manoharbhai Patel College of Arts, Commerce & Science, Deori, Gondia 441901, Maharashtra, India
| | - Prashant P Ingle
- Saibaba Arts and Science College, Parseoni, (Maharashtra)-441105, India
| | - Ahmed A Abdala
- Chemical Engineering Program, Texas A&M University at Qatar, POB 23784, Doha, Qatar
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Kurtz CC, Mitchell S, Nielsen K, Crawford KD, Mueller-Spitz SR. Acute high-dose titanium dioxide nanoparticle exposure alters gastrointestinal homeostasis in mice. J Appl Toxicol 2020; 40:1384-1395. [PMID: 32420653 DOI: 10.1002/jat.3991] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/10/2020] [Accepted: 04/04/2020] [Indexed: 01/09/2023]
Abstract
Human exposure to a wide variety of engineered nanoparticles (NPs) is on the rise and use in common food additives increases gastrointestinal (GI) exposure. Host health is intricately linked to the GI microbiome and immune response. Perturbations in the microbiota can affect energy harvest, trigger inflammation and alter the mucosal barrier leading to various disease states such as obesity and inflammatory bowel diseases. We hypothesized that single high-dose titanium dioxide (TiO2 ) NP exposure in mice would lead to dysbiosis and stimulate mucus production and local immune populations. Juvenile mice (9-10 weeks) were gavaged with 1 g/kg TiO2 NPs and examined for changes in mucosa-associated bacteria abundance, inflammatory cytokines, mucin expression and body mass. Our data provide support that TiO2 NP ingestion alters the GI microbiota and host defenses promoting metabolic disruption and subsequently weight gain in mice.
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Affiliation(s)
- Courtney C Kurtz
- Department of Biology, University of Wisconsin Oshkosh, Oshkosh, Wisconsin, US
| | - Samantha Mitchell
- Department of Biology, University of Wisconsin Oshkosh, Oshkosh, Wisconsin, US
| | - Kaitlyn Nielsen
- Department of Biology, University of Wisconsin Oshkosh, Oshkosh, Wisconsin, US
| | - Kevin D Crawford
- Department of Chemistry, University of Wisconsin Oshkosh, Oshkosh, Wisconsin, US.,Sustainability Institute for Regional Transformations, University of Wisconsin Oshkosh, Oshkosh, Wisconsin, US
| | - Sabrina R Mueller-Spitz
- Department of Biology, University of Wisconsin Oshkosh, Oshkosh, Wisconsin, US.,Sustainability Institute for Regional Transformations, University of Wisconsin Oshkosh, Oshkosh, Wisconsin, US
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Abstract
PurposeNanotechnology as an emerging area if adequately harnessed could revolutionise food packaging and food processing industry worldwide. Although several benefits of nano-materials or particles in food packaging have been suggested, potential risks and health hazards of nano-materials or particles are possible as a result of migration of their particles into food materials. The purpose of this review therefore assessed nanotechnology and its applications in food packaging, consumer acceptability of nano-packaged foods and potential hazards and safety issues in nano-packaged foods.Design/methodology/approachThis review takes a critical assessment of previous literature on nanotechnology and its impact on food packaging, consumer health and safety.FindingsApplications of nanotechnology in food packaging could be divided into three main divisions: improved packaging, which involves mixing nano-materials into polymers matrix to improve temperature, humidity and gas barrier resistance of the packaging materials. Active packaging deals with direct interaction between nano-materials used for packaging and the food to protect it as anti-microbial or oxygen or ultra violet scavengers. Smart packaging could be used to sense biochemical or microbial changes in foods, as well as a tracker for food safety, to prevent food counterfeit and adulteration. The review also discussed bio-based food packaging which is biodegradable. Bio-based packaging could serve as veritable alternative to conventional packaging which is non-degradable plastic polymers which are not environmental friendly and could pose a threat to the environment. However, bio-based packaging could reduce material waste, elongate shelf life and enhance food quality. However, several challenges are envisaged in the use of nano-materials in food packaging due to knowledge gaps, possible interaction with food products and possible health risks that could result from the nano-materials used for food packaging.Originality/valueThe increase in growth and utilisation of nanotechnology signifies wide use of nano-materials especially in the food sector with arrays of potential benefits in the areas of food safety and quality, micronutrients and bioactive ingredients delivery, food processing and in packaging Active studies are being carried out to develop innovative packages such as smart, intelligent and active food packaging to enhance effective and efficient packaging, as well as balanced environmental issues. This review looks at the future of nano-packaged foodsvis-à-visthe roles played by stakeholders such as governments, regulatory agencies and manufacturers in looking into consumer health and safety issues related to the application of nano-materials in food packaging.
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In deep evaluation of the neurotoxicity of orally administered TiO 2 nanoparticles. Brain Res Bull 2019; 155:119-128. [PMID: 31715315 DOI: 10.1016/j.brainresbull.2019.10.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 07/30/2019] [Accepted: 10/16/2019] [Indexed: 11/20/2022]
Abstract
Titanium dioxide nanoparticles were widely used in food as dietary supplements, in drugs, in toothpaste, ect. Few numbers of studies were interested to the neurotoxicity of TiO2 NPs through oral pathway. The present study aims firstly to understand the connection between the physicochemical properties of TiO2 NPs and their associated toxicological oral pathway by evaluation the colloidal stability of TiO2 NPs over time in different media simulating physiological gastric, intestinal and serum conditions at 37 °C to be close to the oral administraton. Secondly, this study aims to evaluate the neurotoxicity of a subchronic intragastric administration of TiO2 NPs to rats. Different doses of anatase TiO2 NPs were administrated to Wistar rats every day for consecutives eight weeks. Titanium (Ti) content in brain, oxidative antioxidant biomarkers, lipid peroxidation, nitric oxide (NO) levels, tumor necrosis factor-alpha (TNF-α) levels, histophatological changes, degenerated and apoptosis neurons were investigated. Results suggested that TiO2 NPs can reach the brain and cross the brain blood barrier (BBB) to been accumulated in the brain of rats causing cerebral oxidative stress damage, increasing NO levels and histopathological injury. At higher dose, we observed the most cerebral injury by the highest accumulation of Ti and by the remarkable increase of TNF-α besides to the most increase of degenerated and apoptosis neurons in the brain of exposed rats. TiO2 NPs led to a neurotoxic damage accompanied by the increase of degenerated and apoptotic neurons in cerebral cortex.
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Blevins LK, Crawford RB, Bach A, Rizzo MD, Zhou J, Henriquez JE, Khan DMIO, Sermet S, Arnold LL, Pennington KL, Souza NP, Cohen SM, Kaminski NE. Evaluation of immunologic and intestinal effects in rats administered an E 171-containing diet, a food grade titanium dioxide (TiO 2). Food Chem Toxicol 2019; 133:110793. [PMID: 31473338 PMCID: PMC6775638 DOI: 10.1016/j.fct.2019.110793] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 08/22/2019] [Accepted: 08/24/2019] [Indexed: 12/13/2022]
Abstract
The toxicity of dietary E 171, a food grade titanium dioxide was evaluated. A recent study reported rats receiving E 171 in water developed inflammation and aberrant crypt foci (ACF) in the gastrointestinal tract. Here, rats received food containing E 171 (7 or 100 days). The 100-day study included feeding E 171 after dimethylhydrazine (DMH) or vehicle only pretreatment. Food consumption was similar between treatment groups with maximum total cumulative E 171 exposure being 2617 mg/kg in 7 days and 29,400 mg/kg in 100 days. No differences were observed due to E 171 in the percentage of dendritic, CD4+ T or Treg cells within Peyer's patches or the periphery, or in cytokine production in plasma, sections of jejunum, and colon in 7- or 100-day E 171 alone fed rats. Differences were observed for IL-17A in colon (400 ppm E 171 + DMH) and IL-12p70 in plasma (40 ppm E 171 + DMH). E 171 had no effect on histopathologic evaluations of small and large intestines, liver, spleen, lungs, or testes, and no effects on ACF, goblet cell numbers, or colonic gland length. Dietary E 171 administration (7- or 100-day), even at high doses, produced no effect on the immune parameters or tissue morphology.
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Affiliation(s)
- Lance K Blevins
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA
| | - Robert B Crawford
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA
| | - Anthony Bach
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Center for Research on Ingredient Safety, Michigan State University, East Lansing, MI, USA
| | - Michael D Rizzo
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Cell and Molecular Biology Program, Michigan State University, East Lansing, MI, USA
| | - Jiajun Zhou
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, MI, USA
| | - Joseph E Henriquez
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA
| | - D M Isha Olive Khan
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA
| | - Sera Sermet
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA
| | - Lora L Arnold
- University of Nebraska Medical Center, Omaha, NE, USA
| | | | | | - Samuel M Cohen
- University of Nebraska Medical Center, Omaha, NE, USA; Havlik-Wall Professor of Oncology, USA
| | - Norbert E Kaminski
- Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Center for Research on Ingredient Safety, Michigan State University, East Lansing, MI, USA; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
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Abo‐zeid Y, Williams GR. The potential anti‐infective applications of metal oxide nanoparticles: A systematic review. WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY 2019; 12:e1592. [DOI: 10.1002/wnan.1592] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Revised: 09/01/2019] [Accepted: 09/04/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Yasmin Abo‐zeid
- School of Pharmacy Helwan University Cairo Egypt
- UCL School of Pharmacy University College London London UK
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Tian Q, Li Y, Jiang S, An L, Lin J, Wu H, Huang P, Yang S. Tumor pH-Responsive Albumin/Polyaniline Assemblies for Amplified Photoacoustic Imaging and Augmented Photothermal Therapy. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2019; 15:e1902926. [PMID: 31448572 DOI: 10.1002/smll.201902926] [Citation(s) in RCA: 75] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 07/28/2019] [Indexed: 05/14/2023]
Abstract
Tumor-microenvironment-responsive theranostics have great potential for precision diagnosis and effective treatment of cancer. Polyaniline (PANI) is the first reported pH-responsive organic photothermal agent and is widely used as a theranostic agent. However, tumor pH-responsive PANI-based theranostic agents are not explored, mainly because the conversion from the emeraldine base (EB) to emeraldine salt (ES) state of PANI requires pH < 4, which is lower than tumor acidic microenvironment. Herein, a tumor pH-responsive PANI-based theranostic agent is designed and prepared for amplified photoacoustic imaging guided augmented photothermal therapy (PTT), through intermolecular acid-base reactions between carboxyl groups of bovine serum albumin (BSA) and imine moieties of PANI. The albumin/PANI assemblies (BSA-PANI) can convert from the EB to ES state at pH < 7, accompanied by the absorbance redshift from visible to near-infrared region. Both in vitro and in vivo results demonstrate that tumor acidic microenvironment can trigger both the photoacoustic imaging (PAI) signal amplification and the PTT efficacy enhancement of BSA-PANI assemblies. This work not only highlights that BSA-PANI assemblies overcome the limitation of low-pH protonation, but also provides a facile assembly strategy for a tumor pH-responsive PANI-based nanoplatform for cancer theranostics.
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Affiliation(s)
- Qiwei Tian
- The Key Laboratory of Resource Chemistry of the Ministry of Education, the Shanghai Key Laboratory of Rare Earth Functional Materials, and the Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors, Shanghai Normal University, Shanghai, 200234, China
| | - Yaping Li
- The Key Laboratory of Resource Chemistry of the Ministry of Education, the Shanghai Key Laboratory of Rare Earth Functional Materials, and the Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors, Shanghai Normal University, Shanghai, 200234, China
| | - Shanshan Jiang
- Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China
| | - Lu An
- The Key Laboratory of Resource Chemistry of the Ministry of Education, the Shanghai Key Laboratory of Rare Earth Functional Materials, and the Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors, Shanghai Normal University, Shanghai, 200234, China
| | - Jiaomin Lin
- The Key Laboratory of Resource Chemistry of the Ministry of Education, the Shanghai Key Laboratory of Rare Earth Functional Materials, and the Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors, Shanghai Normal University, Shanghai, 200234, China
| | - Huixia Wu
- The Key Laboratory of Resource Chemistry of the Ministry of Education, the Shanghai Key Laboratory of Rare Earth Functional Materials, and the Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors, Shanghai Normal University, Shanghai, 200234, China
| | - Peng Huang
- Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China
| | - Shiping Yang
- The Key Laboratory of Resource Chemistry of the Ministry of Education, the Shanghai Key Laboratory of Rare Earth Functional Materials, and the Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors, Shanghai Normal University, Shanghai, 200234, China
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Yokel RA, Hancock ML, Cherian B, Brooks AJ, Ensor ML, Vekaria HJ, Sullivan PG, Grulke EA. Simulated biological fluid exposure changes nanoceria's surface properties but not its biological response. Eur J Pharm Biopharm 2019; 144:252-265. [PMID: 31563633 DOI: 10.1016/j.ejpb.2019.09.023] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 08/26/2019] [Accepted: 09/26/2019] [Indexed: 01/16/2023]
Abstract
Nanoscale cerium dioxide (nanoceria) has industrial applications, capitalizing on its catalytic, abrasive, and energy storage properties. It auto-catalytically cycles between Ce3+ and Ce4+, giving it pro-and anti-oxidative properties. The latter mediates beneficial effects in models of diseases that have oxidative stress/inflammation components. Engineered nanoparticles become coated after body fluid exposure, creating a corona, which can greatly influence their fate and effects. Very little has been reported about nanoceria surface changes and biological effects after pulmonary or gastrointestinal fluid exposure. The study objective was to address the hypothesis that simulated biological fluid (SBF) exposure changes nanoceria's surface properties and biological activity. This was investigated by measuring the physicochemical properties of nanoceria with a citric acid coating (size; morphology; crystal structure; surface elemental composition, charge, and functional groups; and weight) before and after exposure to simulated lung, gastric, and intestinal fluids. SBF-exposed nanoceria biological effect was assessed as A549 or Caco-2 cell resazurin metabolism and mitochondrial oxygen consumption rate. SBF exposure resulted in loss or overcoating of nanoceria's surface citrate, greater nanoceria agglomeration, deposition of some SBF components on nanoceria's surface, and small changes in its zeta potential. The engineered nanoceria and SBF-exposed nanoceria produced no statistically significant changes in cell viability or cellular oxygen consumption rates.
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Affiliation(s)
- Robert A Yokel
- Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536-0596, United States.
| | - Matthew L Hancock
- Chemical and Materials Engineering, University of Kentucky, Lexington, KY 40506-0046, United States.
| | - Benjamin Cherian
- Chemical and Materials Engineering, University of Kentucky, Lexington, KY 40506-0046, United States.
| | - Alexandra J Brooks
- Chemical and Materials Engineering, University of Kentucky, Lexington, KY 40506-0046, United States.
| | - Marsha L Ensor
- Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536-0596, United States.
| | - Hemendra J Vekaria
- Spinal Cord & Brain Injury Research Center, University of Kentucky, Lexington, KY 40536-0509, United States; Department of Neuroscience, University of Kentucky, Lexington, KY 40536-0509, United States.
| | - Patrick G Sullivan
- Spinal Cord & Brain Injury Research Center, University of Kentucky, Lexington, KY 40536-0509, United States; Department of Neuroscience, University of Kentucky, Lexington, KY 40536-0509, United States.
| | - Eric A Grulke
- Chemical and Materials Engineering, University of Kentucky, Lexington, KY 40506-0046, United States.
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Mancuso C, Barisani D. Food additives can act as triggering factors in celiac disease: Current knowledge based on a critical review of the literature. World J Clin Cases 2019; 7:917-927. [PMID: 31119137 PMCID: PMC6509268 DOI: 10.12998/wjcc.v7.i8.917] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Revised: 03/11/2019] [Accepted: 03/16/2019] [Indexed: 02/05/2023] Open
Abstract
Celiac disease (CeD) is an autoimmune disorder, mainly affecting the small intestine, triggered by the ingestion of gluten with the diet in subjects with a specific genetic status. The passage of gluten peptides through the intestinal barrier, the uptake by antigen presenting cells and their presentation to T cells represent essential steps in the pathogenesis of the disease. CeD prevalence varies in different populations, but a tendency to increase has been observed in various studies in recent years. A higher amount of gluten in modern grains could explain this increased frequency, but also food processing could play a role in this phenomenon. In particular, the common use of preservatives such as nanoparticles could intervene in the pathogenesis of CeD, due to their possible effect on the integrity of the intestinal barrier, immune response or microbiota. In fact, these alterations have been reported after exposure to metal nanoparticles, which are commonly used as preservatives or to improve food texture, consistency and color. This review will focus on the interactions between several food additives and the intestine, taking into account data obtained in vitro and in vivo, and analyzing their effect in respect to the development of CeD in genetically predisposed individuals.
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Affiliation(s)
- Clara Mancuso
- Department of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, Monza 20900, Italy
| | - Donatella Barisani
- Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
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Henson TE, Navratilova J, Tennant AH, Bradham KD, Rogers KR, Hughes MF. In vitro intestinal toxicity of copper oxide nanoparticles in rat and human cell models. Nanotoxicology 2019; 13:795-811. [PMID: 30938207 DOI: 10.1080/17435390.2019.1578428] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Human oral exposure to copper oxide nanoparticles (NPs) may occur following ingestion, hand-to-mouth activity, or mucociliary transport following inhalation. This study assessed the cytotoxicity of Cupric (II) oxide (CuO) and Cu2O-polyvinylpyrrolidone (PVP) coated NPs and copper ions in rat (intestine epithelial cells; IEC-6) and human intestinal cells, two- and three-dimensional models, respectively. The effect of pretreatment of CuO NPs with simulated gastrointestinal (GI) fluids on IEC-6 cell cytotoxicity was also investigated. Both dose- and time-dependent decreases in viability of rat and human cells with CuO and Cu2O-PVP NPs and Cu2+ ions was observed. In the rat cells, CuO NPs had greater cytotoxicity. The rat cells were also more sensitive to CuO NPs than the human cells. Concentrations of H2O2 and glutathione increased and decreased, respectively, in IEC-6 cells after a 4-h exposure to CuO NPs, suggesting the formation of reactive oxygen species (ROS). These ROS may have damaged the mitochondrial membrane of the IEC-6 cells causing a depolarization, as a dose-related loss of a fluorescent mitochondrial marker was observed following a 4-h exposure to CuO NPs. Dissolution studies showed that Cu2O-PVP NPs formed soluble Cu whereas CuO NPs essentially remained intact. For GI fluid-treated CuO NPs, there was a slight increase in cytotoxicity at low doses relative to non-treated NPs. In summary, copper oxide NPs were cytotoxic to rat and human intestinal cells in a dose- and time-dependent manner. The data suggests Cu2O-PVP NPs are toxic due to their dissolution to Cu ions, whereas CuO NPs have inherent cytotoxicity, without dissolving to form Cu ions.
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Affiliation(s)
- Taylor E Henson
- a Student Services Contractor at the National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park , NC , USA
| | | | - Alan H Tennant
- c National Health and Environmental Effects Research Laboratory , Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park , NC , USA
| | - Karen D Bradham
- d National Exposure Research Laboratory , Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park , NC , USA
| | - Kim R Rogers
- d National Exposure Research Laboratory , Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park , NC , USA
| | - Michael F Hughes
- c National Health and Environmental Effects Research Laboratory , Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park , NC , USA
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De Matteis V, Cascione M, Toma CC, Pellegrino P, Rizzello L, Rinaldi R. Tailoring Cell Morphomechanical Perturbations Through Metal Oxide Nanoparticles. NANOSCALE RESEARCH LETTERS 2019; 14:109. [PMID: 30923929 PMCID: PMC6439097 DOI: 10.1186/s11671-019-2941-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Accepted: 03/14/2019] [Indexed: 05/17/2023]
Abstract
The nowadays growing use of nanoparticles (NPs) in commercial products does not match a comprehensive understanding of their potential harmfulness. More in vitro investigations are required to address how the physicochemical properties of NPs guide their engulfment within cells and their intracellular trafficking, fate, and toxicity. These nano-bio interactions have not been extensively addressed yet, especially from a mechanical viewpoint. Cell mechanic is a critical indicator of cell health because it regulates processes like cell migration, tissue integrity, and differentiation via cytoskeleton rearrangements. Here, we investigated in vitro the elasticity perturbation of Caco-2 and A549 cell lines, in terms of Young's modulus modification induced by SiO2NPS and TiO2NPS. TiO2NPs demonstrated stronger effects on cell elasticity compared to SiO2NPs, as they induced significant morphological and morphometric changes in actin network. TiO2NPS increased the elasticity in Caco-2 cells, while opposite effects have been observed on A549 cells. These results demonstrate the existence of a correlation between the alteration of cell elasticity and NPs toxicity that depends, in turn, on the NPs physicochemical properties and the specific cell tested.
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Affiliation(s)
- Valeria De Matteis
- Dipartimento di Matematica e Fisica “Ennio De Giorgi”, Università del Salento, Via Arnesano, 73100 Lecce, Italy
| | - Mariafrancesca Cascione
- Dipartimento di Matematica e Fisica “Ennio De Giorgi”, Università del Salento, Via Arnesano, 73100 Lecce, Italy
| | - Chiara Cristina Toma
- Dipartimento di Matematica e Fisica “Ennio De Giorgi”, Università del Salento, Via Arnesano, 73100 Lecce, Italy
| | - Paolo Pellegrino
- Dipartimento di Matematica e Fisica “Ennio De Giorgi”, Università del Salento, Via Arnesano, 73100 Lecce, Italy
| | - Loris Rizzello
- Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ UK
- Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, 08028 Barcelona, Spain
| | - Rosaria Rinaldi
- Dipartimento di Matematica e Fisica “Ennio De Giorgi”, Università del Salento, Via Arnesano, 73100 Lecce, Italy
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Pirsaheb M, Azadi NA, Miglietta ML, Sayadi MH, Blahova J, Fathi M, Mansouri B. Toxicological effects of transition metal-doped titanium dioxide nanoparticles on goldfish (Carassius auratus) and common carp (Cyprinus carpio). CHEMOSPHERE 2019; 215:904-915. [PMID: 30408886 DOI: 10.1016/j.chemosphere.2018.10.111] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 10/15/2018] [Accepted: 10/16/2018] [Indexed: 06/08/2023]
Abstract
The aim of present study was to assess the toxicological effects of transition metal-doped titanium dioxide nanoparticles (TiO2 NPs) on histopathological changes, behavioral patterns, and antioxidant responses of goldfish (Carassius auratus) and common carp (Cyprinus carpio). The synthesized nanoparticles were confirmed by Transmission Electron Microscopy, Field Emission Scanning Electron Microscopy, X-ray diffraction, UV-visible, and Vibration Sample Magnetometer. Fish in four experimental groups exposed to sub-lethal concentrations of pure TiO2 NPs (10 mg L-1), chromium (Cr), iron (Fe), and nickel (Ni) doped TiO2 NPs for seven days. Statistical analysis of oxidative stress responses in gills showed significant differences in superoxide dismutase, total antioxidant capacity, and malondialdehyde parameters between two species and in all parameters than glutathione peroxidase between experimental groups and control group. In intestine, no significant difference was observed among groups, but oxidative responses were markedly different in all parameters among fish species. The histopathological analysis showed hyperplasia, fusion, and aneurism in the gills as well as degeneration, integration of villi, necrosis and erosion of the intestine. Our findings indicated that compare to pure TiO2 NPs, exposure to transition metals-doped TiO2 NPs induced oxidative stress and histopathological changes in both fish species.
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Affiliation(s)
- Maghdad Pirsaheb
- -Research Center for Environmental Determinants of Health (RCEDH), Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Nammam Ali Azadi
- Biostatistics Department, Faculty of Public Health, Iran University of Medical Sciences, Tehran, Iran.
| | | | - Mohammad Hossein Sayadi
- Department of Environmental Sciences, School of Natural Resources and Environment, University of Birjand, Birjand, Iran.
| | - Jana Blahova
- Department of Animal Protection, Welfare and Behaviour, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho tr. 1946/1, 612 42, Brno, Czech Republic.
| | - Mokhtar Fathi
- Animal Sciences Department, Payam Noor University, Sanandaj, Iran.
| | - Borhan Mansouri
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand, Iran.
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Yang X, Feng L, Zhang Y, Hu H, Shi Y, Liang S, Zhao T, Cao L, Duan J, Sun Z. Co-exposure of silica nanoparticles and methylmercury induced cardiac toxicity in vitro and in vivo. THE SCIENCE OF THE TOTAL ENVIRONMENT 2018; 631-632:811-821. [PMID: 29727991 DOI: 10.1016/j.scitotenv.2018.03.107] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 02/11/2018] [Accepted: 03/09/2018] [Indexed: 06/08/2023]
Abstract
The released nanoparticles into environment can potentially interact with pre-existing pollution, maybe causing higher toxicity. As such, assessment of their joint toxic effects is necessary. This study was to investigate the co-exposure cardiac toxicity of silica nanoparticles (SiNPs) and methylmercury (MeHg). Factorial design was used to determine the potential joint action type. In vitro study, human cardiomyocytes (AC16) were exposed to SiNPs and MeHg alone or the combination. Higher toxicity was observed on cell viability, cell membrane damage in co-exposure compared with single exposure and control. The co-exposure enhanced the ROS, MDA generation and reduced the activity of SOD and GSH-Px. In addition, the co-exposure induced much higher cellular apoptotic rate in AC16. In vivo study, after SD rats exposed to SiNPs and MeHg and their mixture by intratracheal instillation for 30days, pathological changes (myocardial interstitial edema) of heart were occurred in co-exposure compared with single exposure and control. Moreover obvious ultra-structural changes, including myofibril disorder, myocardial gap expansion, and mitochondrial damage were observed in co-exposure group. The activity of myocardial enzymes, including CK-MB, ANP, BNP and cTnT, were significantly elevated in co-exposure group of rat serum. Meanwhile, the cardiac injury-linked proteins expression showed an increase in SERCA2 and decreased levels of cTnT, ANP and BNP in co-exposure group. Factorial design analysis demonstrated that additive and synergistic interactions were responsible for the co-exposure cardiac toxicity in vitro and vivo. In summary, our results showed severe cardiac toxicity induced by co-exposure of SiNPs and MeHg in both cardiomycytes and heart. It will help to clarify the potential cardiovascular toxicity in regards to combined exposure pollutions.
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Affiliation(s)
- Xiaozhe Yang
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China
| | - Lin Feng
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China
| | - Yannan Zhang
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China
| | - Hejing Hu
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China
| | - Yanfeng Shi
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China
| | - Shuang Liang
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China
| | - Tong Zhao
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China
| | - Lige Cao
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China
| | - Junchao Duan
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China.
| | - Zhiwei Sun
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China.
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Sohal IS, O'Fallon KS, Gaines P, Demokritou P, Bello D. Ingested engineered nanomaterials: state of science in nanotoxicity testing and future research needs. Part Fibre Toxicol 2018; 15:29. [PMID: 29970114 PMCID: PMC6029122 DOI: 10.1186/s12989-018-0265-1] [Citation(s) in RCA: 105] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 06/14/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Engineered nanomaterials (ENM) are used extensively in food products to fulfill a number of roles, including enhancement of color and texture, for nutritional fortification, enhanced bioavailability, improved barrier properties of packaging, and enhanced food preservation. Safety assessment of ingested engineered nanomaterials (iENM) has gained interest in the nanotoxicology community in recent years. A variety of test systems and approaches have been used for such evaluations, with in vitro monoculture cell models being the most common test systems, owing to their low cost and ease-of-use. The goal of this review is to systematically assess the current state of science in toxicological testing of iENM, with particular emphasis on model test systems, their physiological relevance, methodological strengths and challenges, realistic doses (ranges and rates), and then to identify future research needs and priorities based on these assessments. METHODS Extensive searches were conducted in Google Scholar, PubMed and Web of Science to identify peer-reviewed literature on safety assessment of iENM over the last decade, using keywords such as "nanoparticle", "food", "toxicity", and combinations thereof. Relevant literature was assessed based on a set of criteria that included the relevance of nanomaterials tested; ENM physicochemical and morphological characterization; dispersion and dosimetry in an in vitro system; dose ranges employed, the rationale and dose realism; dissolution behavior of iENM; endpoints tested, and the main findings of each study. Observations were entered into an excel spreadsheet, transferred to Origin, from where summary statistics were calculated to assess patterns, trends, and research gaps. RESULTS A total of 650 peer-reviewed publications were identified from 2007 to 2017, of which 39 were deemed relevant. Only 21% of the studies used food grade nanomaterials for testing; adequate physicochemical and morphological characterization was performed in 53% of the studies. All in vitro studies lacked dosimetry and 60% of them did not provide a rationale for the doses tested and their relevance. Only 12% of the studies attempted to consider the dissolution kinetics of nanomaterials. Moreover, only 1 study attempted to prepare and characterize standardized nanoparticle dispersions. CONCLUSION We identified 5 clusters of factors deemed relevant to nanotoxicology of food-grade iENM: (i) using food-grade nanomaterials for toxicity testing; (ii) performing comprehensive physicochemical and morphological characterization of iENM in the dry state, (iii) establishing standard NP dispersions and their characterization in cell culture medium, (iv) employing realistic dose ranges and standardized in vitro dosimetry models, and (v) investigating dissolution kinetics and biotransformation behavior of iENM in synthetic media representative of the gastrointestinal (GI) tract fluids, including analyses in a fasted state and in the presence of a food matrix. We discussed how these factors, when not considered thoughtfully, could influence the results and generalizability of in vitro and in vivo testing. We conclude with a set of recommendations to guide future iENM toxicity studies and to develop/adopt more relevant in vitro model systems representative of in vivo animal and human iENM exposure scenarios.
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Affiliation(s)
- Ikjot Singh Sohal
- Biomedical Engineering & Biotechnology Program, University of Massachusetts Lowell, Lowell, MA, 01854, USA.
| | - Kevin S O'Fallon
- Natick Soldier Research, Development and Engineering Center, Natick, MA, 01760, USA
| | - Peter Gaines
- Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA, 01854, USA
| | - Philip Demokritou
- Harvard T.H. Chan School of Public Health, Department of Environmental Health and the Harvard Center for Nanotechnology and Nanotoxicology, Boston, MA, 02115, USA
| | - Dhimiter Bello
- Biomedical Engineering & Biotechnology Program, University of Massachusetts Lowell, Lowell, MA, 01854, USA.
- Harvard T.H. Chan School of Public Health, Department of Environmental Health and the Harvard Center for Nanotechnology and Nanotoxicology, Boston, MA, 02115, USA.
- Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, 883 Broadway Street, Dugan 110-S, Lowell, MA, 01854, USA.
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Winkler HC, Notter T, Meyer U, Naegeli H. Critical review of the safety assessment of titanium dioxide additives in food. J Nanobiotechnology 2018; 16:51. [PMID: 29859103 PMCID: PMC5984422 DOI: 10.1186/s12951-018-0376-8] [Citation(s) in RCA: 122] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Accepted: 05/18/2018] [Indexed: 01/06/2023] Open
Abstract
Nanomaterial engineering provides an important technological advance that offers substantial benefits for applications not only in the production and processing, but also in the packaging and storage of food. An expanding commercialization of nanomaterials as part of the modern diet will substantially increase their oral intake worldwide. While the risk of particle inhalation received much attention, gaps of knowledge exist regarding possible adverse health effects due to gastrointestinal exposure. This problem is highlighted by pigment-grade titanium dioxide (TiO2), which confers a white color and increased opacity with an optimal particle diameter of 200-300 nm. However, size distribution analyses showed that batches of food-grade TiO2 always comprise a nano-sized fraction as inevitable byproduct of the manufacturing processes. Submicron-sized TiO2 particles, in Europe listed as E 171, are widely used as a food additive although the relevant risk assessment has never been satisfactorily completed. For example, it is not possible to derive a safe daily intake of TiO2 from the available long-term feeding studies in rodents. Also, the use of TiO2 particles in the food sector leads to highest exposures in children, but only few studies address the vulnerability of this particular age group. Extrapolation of animal studies to humans is also problematic due to knowledge gaps as to local gastrointestinal effects of TiO2 particles, primarily on the mucosa and the gut-associated lymphoid system. Tissue distributions after oral administration of TiO2 differ from other exposure routes, thus limiting the relevance of data obtained from inhalation or parenteral injections. Such difficulties and uncertainties emerging in the retrospective assessment of TiO2 particles exemplify the need for a fit-to-purpose data requirement for the future evaluation of novel nano-sized or submicron-sized particles added deliberately to food.
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Affiliation(s)
- Hans Christian Winkler
- Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Schmelzbergstrasse 7, 8092 Zurich, Switzerland
| | - Tina Notter
- Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Winterthurerstrasse 260, 8057 Zurich, Switzerland
| | - Urs Meyer
- Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Winterthurerstrasse 260, 8057 Zurich, Switzerland
| | - Hanspeter Naegeli
- Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Winterthurerstrasse 260, 8057 Zurich, Switzerland
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Ma Z, Garrido-Maestu A, Lee C, Chon J, Jeong D, Yue Y, Sung K, Park Y, Jeong KC. Comprehensive in vitro and in vivo risk assessments of chitosan microparticles using human epithelial cells and Caenorhabditis elegans. JOURNAL OF HAZARDOUS MATERIALS 2018; 341:248-256. [PMID: 28797941 DOI: 10.1016/j.jhazmat.2017.07.071] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 07/18/2017] [Accepted: 07/31/2017] [Indexed: 06/07/2023]
Abstract
The safety of using nano- and microparticles is a developing concern. In this study, we conducted risk assessments of chitosan microparticles (CMs) using in vitro human epithelial cell lines and in vivo animal model, Caenorhabditis elegans. After engineering of various CMs, we screened four CMs based on antimicrobial activity, which is a potential usage for disease treatment caused by multidrug resistant bacteria, and evaluated for risk assessments. CMs, with strong antimicrobial activity, and inorganic nanoparticles (SiO2, TiO2, and ZnO) did not cause toxicity in human cells measured by cell membrane integrity, mitochondria activity, and reactive oxygen species concentration. However, when applied to C. elegans, only CMs generated with low molecular weight chitosan and tripolyphosphate at 0.1% did not affect the lifespan, while the other CMs and inorganic nanoparticles shortened the lifespan, suggesting that they may cause subtle toxicity. These results suggest that C. elegans could be a sensitive animal model to measure low level of toxicity of nano- and microparticles. Taken together, although CMs do not cause toxicity at working concentrations of antimicrobial activity in human epithelial cells, they may cause toxicity at high concentration, suggesting that nano- and microparicles should be thoroughly investigated before they are applied.
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Affiliation(s)
- Zhengxin Ma
- Emerging Pathogens Institute, University of Florida, Gainesville, FL 32611, United States; Department of Animal Sciences, University of Florida, Gainesville, FL 32611, United States
| | - Alejandro Garrido-Maestu
- Emerging Pathogens Institute, University of Florida, Gainesville, FL 32611, United States; Department of Animal Sciences, University of Florida, Gainesville, FL 32611, United States
| | - Choonghee Lee
- Emerging Pathogens Institute, University of Florida, Gainesville, FL 32611, United States; Department of Animal Sciences, University of Florida, Gainesville, FL 32611, United States
| | - Jungwhan Chon
- Division of Microbiology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, United States
| | - Daehee Jeong
- F. W. Buchholz High School, Gainesville, FL 32606, United States
| | - Yiren Yue
- Department of Food Science, University of Massachusetts, Amherst, MA 01002, United States
| | - Kidon Sung
- Division of Microbiology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, United States
| | - Yeonhwa Park
- Department of Food Science, University of Massachusetts, Amherst, MA 01002, United States
| | - Kwangcheol Casey Jeong
- Emerging Pathogens Institute, University of Florida, Gainesville, FL 32611, United States; Department of Animal Sciences, University of Florida, Gainesville, FL 32611, United States.
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Gu T, Yao C, Zhang K, Li C, Ding L, Huang Y, Wu M, Wang Y. Toxic effects of zinc oxide nanoparticles combined with vitamin C and casein phosphopeptides on gastric epithelium cells and the intestinal absorption of mice. RSC Adv 2018; 8:26078-26088. [PMID: 35541949 PMCID: PMC9082813 DOI: 10.1039/c8ra03693d] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 06/25/2018] [Indexed: 12/23/2022] Open
Abstract
Vitamin C is more powerful than casein phosphopeptides at controlling the combined toxic effects induced by ZnO NPs on gastric epithelium cells and intestinal absorption in mice.
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Affiliation(s)
- Tianjiao Gu
- Institute of Nanochemistry and Nanobiology
- Shanghai University
- Shanghai
- China
| | - Chenjie Yao
- Institute of Nanochemistry and Nanobiology
- Shanghai University
- Shanghai
- China
| | - Kangkang Zhang
- Institute of Nanochemistry and Nanobiology
- Shanghai University
- Shanghai
- China
| | - Chenchen Li
- Institute of Nanochemistry and Nanobiology
- Shanghai University
- Shanghai
- China
| | - Lin Ding
- Institute of Nanochemistry and Nanobiology
- Shanghai University
- Shanghai
- China
| | - Yanan Huang
- Institute of Nanochemistry and Nanobiology
- Shanghai University
- Shanghai
- China
| | - Minghong Wu
- School of Environmental and Chemical Engineering
- Shanghai University
- Shanghai
- China
| | - Yanli Wang
- Institute of Nanochemistry and Nanobiology
- Shanghai University
- Shanghai
- China
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Bouwmeester H, van der Zande M, Jepson MA. Effects of food-borne nanomaterials on gastrointestinal tissues and microbiota. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2018; 10:e1481. [PMID: 28548289 PMCID: PMC5810149 DOI: 10.1002/wnan.1481] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Revised: 05/02/2017] [Accepted: 05/04/2017] [Indexed: 12/26/2022]
Abstract
Ingestion of engineered nanomaterials is inevitable due to their addition to food and prevalence in food packaging and domestic products such as toothpaste and sun cream. In the absence of robust dosimetry and particokinetic data, it is currently challenging to accurately assess the potential toxicity of food-borne nanomaterials. Herein, we review current understanding of gastrointestinal uptake mechanisms, consider some data on the potential for toxicity of the most commonly encountered classes of food-borne nanomaterials (including TiO2 , SiO2, ZnO, and Ag nanoparticles), and discuss the potential impact of the luminal environment on nanoparticle properties and toxicity. Much of our current understanding of gastrointestinal nanotoxicology is derived from increasingly sophisticated epithelial models that augment in vivo studies. In addition to considering the direct effects of food-borne nanomaterials on gastrointestinal tissues, including the potential role of chronic nanoparticle exposure in development of inflammatory diseases, we also discuss the potential for food-borne nanomaterials to disturb the normal balance of microbiota within the gastrointestinal tract. The latter possibility warrants close attention given the increasing awareness of the critical role of microbiota in human health and the known impact of some food-borne nanomaterials on bacterial viability. WIREs Nanomed Nanobiotechnol 2018, 10:e1481. doi: 10.1002/wnan.1481 This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.
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Affiliation(s)
- Hans Bouwmeester
- Division of ToxicologyWageningen University and ResearchWageningenThe Netherlands
- RIKILT ‐ Wageningen University and ResearchWageningenThe Netherlands
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Yang P, Hong W, Zhou P, Chen B, Xu H. Nano and bulk ZnO trigger diverse Zn-transport-related gene transcription in distinct regions of the small intestine in mice after oral exposure. Biochem Biophys Res Commun 2017; 493:1364-1369. [DOI: 10.1016/j.bbrc.2017.09.165] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Accepted: 09/29/2017] [Indexed: 12/30/2022]
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De Matteis V. Exposure to Inorganic Nanoparticles: Routes of Entry, Immune Response, Biodistribution and In Vitro/In Vivo Toxicity Evaluation. TOXICS 2017; 5:toxics5040029. [PMID: 29051461 PMCID: PMC5750557 DOI: 10.3390/toxics5040029] [Citation(s) in RCA: 167] [Impact Index Per Article: 20.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 10/09/2017] [Accepted: 10/09/2017] [Indexed: 12/12/2022]
Abstract
The development of different kinds of nanoparticles, showing different physico-chemical properties, has fostered their large use in many fields, including medicine. As a consequence, inorganic nanoparticles (e.g., metals or semiconductors), have raised issues about their potential toxicity. The scientific community is investigating the toxicity mechanisms of these materials, in vitro and in vivo, in order to provide accurate references concerning their use. This review will give the readers a thorough exploration on the entry mechanisms of inorganic nanoparticles in the human body, such as titanium dioxide nanoparticles (TiO₂NPs), silicon dioxide nanoparticles (SiO₂NPs), zinc oxide nanoparticles (ZnONPs), silver nanoparticles (AgNPs), gold nanoparticles (AuNPs) and quantum dots (QDsNPs). In addition, biodistribution, the current trends and novelties of in vitro and in vivo toxicology studies will be discussed, with a particular focus on immune response.
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Affiliation(s)
- Valeria De Matteis
- Dipartimento di Matematica e Fisica "Ennio De Giorgi", Università del Salento, Via Arnesano, 73100 Lecce, Italy.
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Sieg H, Kästner C, Krause B, Meyer T, Burel A, Böhmert L, Lichtenstein D, Jungnickel H, Tentschert J, Laux P, Braeuning A, Estrela-Lopis I, Gauffre F, Fessard V, Meijer J, Luch A, Thünemann AF, Lampen A. Impact of an Artificial Digestion Procedure on Aluminum-Containing Nanomaterials. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2017; 33:10726-10735. [PMID: 28903564 DOI: 10.1021/acs.langmuir.7b02729] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
Aluminum has gathered toxicological attention based on relevant human exposure and its suspected hazardous potential. Nanoparticles from food supplements or food contact materials may reach the human gastrointestinal tract. Here, we monitored the physicochemical fate of aluminum-containing nanoparticles and aluminum ions when passaging an in vitro model of the human gastrointestinal tract. Small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), ion beam microscopy (IBM), secondary ion beam mass spectrometry (TOF-SIMS), and inductively coupled plasma mass spectrometry (ICP-MS) in the single-particle mode were employed to characterize two aluminum-containing nanomaterials with different particle core materials (Al0, γAl2O3) and soluble AlCl3. Particle size and shape remained unchanged in saliva, whereas strong agglomeration of both aluminum nanoparticle species was observed at low pH in gastric fluid together with an increased ion release. The levels of free aluminum ions decreased in intestinal fluid and the particles deagglomerated, thus liberating primary particles again. Dissolution of nanoparticles was limited and substantial changes of their shape and size were not detected. The amounts of particle-associated phosphorus, chlorine, potassium, and calcium increased in intestinal fluid, as compared to nanoparticles in standard dispersion. Interestingly, nanoparticles were found in the intestinal fluid after addition of ionic aluminum. We provide a comprehensive characterization of the fate of aluminum nanoparticles in simulated gastrointestinal fluids, demonstrating that orally ingested nanoparticles probably reach the intestinal epithelium. The balance between dissolution and de novo complex formation should be considered when evaluating nanotoxicological experiments.
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Affiliation(s)
- Holger Sieg
- German Federal Institute for Risk Assessment , Department of Food Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany
| | - Claudia Kästner
- Bundesanstalt für Materialforschung und -prüfung (BAM) , Unter den Eichen 87, 12205 Berlin, Germany
| | - Benjamin Krause
- German Federal Institute for Risk Assessment , Department of Chemical and Product Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany
| | - Thomas Meyer
- Institute of Medical Physics and Biophysics, Leipzig University , Härtelstrasse 16-18, 04275 Leipzig, Germany
| | - Agnès Burel
- Institut des Sciences Chimiques de Rennes, UMR-CNRS 6226, Université de Rennes, 35700 Rennes, France
| | - Linda Böhmert
- German Federal Institute for Risk Assessment , Department of Food Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany
| | - Dajana Lichtenstein
- German Federal Institute for Risk Assessment , Department of Food Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany
| | - Harald Jungnickel
- German Federal Institute for Risk Assessment , Department of Chemical and Product Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany
| | - Jutta Tentschert
- German Federal Institute for Risk Assessment , Department of Chemical and Product Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany
| | - Peter Laux
- German Federal Institute for Risk Assessment , Department of Chemical and Product Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany
| | - Albert Braeuning
- German Federal Institute for Risk Assessment , Department of Food Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany
| | - Irina Estrela-Lopis
- Institute of Medical Physics and Biophysics, Leipzig University , Härtelstrasse 16-18, 04275 Leipzig, Germany
| | - Fabienne Gauffre
- Institut des Sciences Chimiques de Rennes, UMR-CNRS 6226, Université de Rennes, 35700 Rennes, France
| | - Valérie Fessard
- Fougères Laboratory, Toxicology of contaminants unit, ANSES, French Agency for Food, Environmental and Occupational Health and Safety, 10B rue Claude Bourgelat, 35306 Cedex, Fougères, France
| | - Jan Meijer
- Felix Bloch Institute for Solid State Physics, Leipzig University , Linnéstraße 5, 04103 Leipzig, Germany
| | - Andreas Luch
- German Federal Institute for Risk Assessment , Department of Chemical and Product Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany
| | - Andreas F Thünemann
- Bundesanstalt für Materialforschung und -prüfung (BAM) , Unter den Eichen 87, 12205 Berlin, Germany
| | - Alfonso Lampen
- German Federal Institute for Risk Assessment , Department of Food Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany
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Murugadoss S, Lison D, Godderis L, Van Den Brule S, Mast J, Brassinne F, Sebaihi N, Hoet PH. Toxicology of silica nanoparticles: an update. Arch Toxicol 2017; 91:2967-3010. [PMID: 28573455 PMCID: PMC5562771 DOI: 10.1007/s00204-017-1993-y] [Citation(s) in RCA: 287] [Impact Index Per Article: 35.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 05/18/2017] [Indexed: 12/18/2022]
Abstract
Large-scale production and use of amorphous silica nanoparticles (SiNPs) have increased the risk of human exposure to SiNPs, while their health effects remain unclear. In this review, scientific papers from 2010 to 2016 were systematically selected and sorted based on in vitro and in vivo studies: to provide an update on SiNPs toxicity and to address the knowledge gaps indicated in the review of Napierska (Part Fibre Toxicol 7:39, 2010). Toxicity of SiNPs in vitro is size, dose, and cell type dependent. SiNPs synthesized by wet route exhibited noticeably different biological effects compared to thermal route-based SiNPs. Amorphous SiNPs (particularly colloidal and stöber) induced toxicity via mechanisms similar to crystalline silica. In vivo, route of administration and physico-chemical properties of SiNPs influences the toxicokinetics. Adverse effects were mainly observed in acutely exposed animals, while no significant signs of toxicity were noted in chronically dosed animals. The correlation between in vitro and in vivo toxicity remains less well established mainly due to improper-unrealistic-dosing both in vitro and in vivo. In conclusion, notwithstanding the multiple studies published in recent years, unambiguous linking of physico-chemical properties of SiNPs types to toxicity, bioavailability, or human health effects is not yet possible.
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Affiliation(s)
- Sivakumar Murugadoss
- Unit for Lung Toxicology, Katholieke Universiteit Leuven, Herestraat 49, O&N1, Room: 07.702, box 706, 3000 Louvain, Belgium
| | - Dominique Lison
- Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Université Catholique de Louvain, Avenue E. Mounier 52/B1.52.12, 1200 Brussels, Belgium
| | - Lode Godderis
- Department of Occupational, Environmental and Insurance Medicine, Katholieke Universiteit Leuven, Kapucijnenvoer 35 block d, box 7001, 3000 Louvain, Belgium
| | - Sybille Van Den Brule
- Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Université Catholique de Louvain, Avenue E. Mounier 52/B1.52.12, 1200 Brussels, Belgium
| | - Jan Mast
- EM-unit, Center for Veterinary and Agrochemical Studies and Research (CODA-CERVA), Groeselenberg 99, Uccle, 1180 Brussels, Belgium
| | - Frederic Brassinne
- EM-unit, Center for Veterinary and Agrochemical Studies and Research (CODA-CERVA), Groeselenberg 99, Uccle, 1180 Brussels, Belgium
| | - Noham Sebaihi
- General Quality and Safety, Metrology Department, National Standards, North Gate-Office 2A29, Bd du Roi Albert II, 16, 1000 Brussels, Belgium
| | - Peter H. Hoet
- Unit for Lung Toxicology, Katholieke Universiteit Leuven, Herestraat 49, O&N1, Room: 07.702, box 706, 3000 Louvain, Belgium
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Böhmert L, Laux P, Luch A, Braeuning A, Lampen A. Nanomaterialien in Lebensmitteln – toxikologische Eigenschaften und Risikobewertung. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2017; 60:722-727. [DOI: 10.1007/s00103-017-2559-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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von Moos LM, Schneider M, Hilty FM, Hilbe M, Arnold M, Ziegler N, Mato DS, Winkler H, Tarik M, Ludwig C, Naegeli H, Langhans W, Zimmermann MB, Sturla SJ, Trantakis IA. Iron phosphate nanoparticles for food fortification: Biological effects in rats and human cell lines. Nanotoxicology 2017; 11:496-506. [PMID: 28368214 DOI: 10.1080/17435390.2017.1314035] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Nanotechnology offers new opportunities for providing health benefits in foods. Food fortification with iron phosphate nanoparticles (FePO4 NPs) is a promising new approach to reducing iron deficiency because FePO4 NPs combine high bioavailability with superior sensory performance in difficult to fortify foods. However, their safety remains largely untested. We fed rats for 90 days diets containing FePO4 NPs at doses at which iron sulfate (FeSO4), a commonly used food fortificant, has been shown to induce adverse effects. Feeding did not result in signs of toxicity, including oxidative stress, organ damage, excess iron accumulation in organs or histological changes. These safety data were corroborated by evidence that NPs were taken up by human gastrointestinal cell lines without reducing cell viability or inducing oxidative stress. Our findings suggest FePO4 NPs appear to be as safe for ingestion as FeSO4.
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Affiliation(s)
- Lea M von Moos
- a Department of Health Sciences and Technology , ETH Zürich , Switzerland
| | - Mirjam Schneider
- a Department of Health Sciences and Technology , ETH Zürich , Switzerland
| | - Florentine M Hilty
- a Department of Health Sciences and Technology , ETH Zürich , Switzerland
| | - Monika Hilbe
- b Institute of Veterinary Pathology, University of Zurich-Vetsuisse , Switzerland
| | - Myrtha Arnold
- a Department of Health Sciences and Technology , ETH Zürich , Switzerland
| | - Nathalie Ziegler
- a Department of Health Sciences and Technology , ETH Zürich , Switzerland
| | - Diogo Sales Mato
- a Department of Health Sciences and Technology , ETH Zürich , Switzerland
| | - Hans Winkler
- c Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse , Switzerland
| | - Mohamed Tarik
- d Energy and Environment Research Division , Paul Scherrer Institute (PSI) , Switzerland
| | - Christian Ludwig
- d Energy and Environment Research Division , Paul Scherrer Institute (PSI) , Switzerland.,e E´cole Polytechnique Fe´de´rale de Lausanne (EPFL), ENAC-IIE , Lausanne , Switzerland
| | - Hanspeter Naegeli
- c Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse , Switzerland
| | - Wolfgang Langhans
- a Department of Health Sciences and Technology , ETH Zürich , Switzerland
| | | | - Shana J Sturla
- a Department of Health Sciences and Technology , ETH Zürich , Switzerland
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Fruijtier-Pölloth C. The safety of nanostructured synthetic amorphous silica (SAS) as a food additive (E 551). Arch Toxicol 2016; 90:2885-2916. [PMID: 27699444 PMCID: PMC5104814 DOI: 10.1007/s00204-016-1850-4] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 09/08/2016] [Indexed: 11/30/2022]
Abstract
KEY MESSAGES Particle sizes of E 551 products are in the micrometre range. The typical external diameters of the constituent particles (aggregates) are greater than 100 nm. E 551 does not break down under acidic conditions such as in the stomach, but may release dissolved silica in environments with higher pH such as the intestinal tract. E 551 is one of the toxicologically most intensively studied substances and has not shown any relevant systemic or local toxicity after oral exposure. Synthetic amorphous silica (SAS) meeting the specifications for use as a food additive (E 551) is and has always been produced by the same two production methods: the thermal and the wet processes, resulting in E 551 products consisting of particles typically in the micrometre size range. The constituent particles (aggregates) are typically larger than 100 nm and do not contain discernible primary particles. Particle sizes above 100 nm are necessary for E 551 to fulfil its technical function as spacer between food particles, thus avoiding the caking of food particles. Based on an in-depth review of the available toxicological information and intake data, it is concluded that the SAS products specified for use as food additive E 551 do not cause adverse effects in oral repeated-dose studies including doses that exceed current OECD guideline recommendations. In particular, there is no evidence for liver toxicity after oral intake. No adverse effects have been found in oral fertility and developmental toxicity studies, nor are there any indications from in vivo studies for an immunotoxic or neurotoxic effect. SAS is neither mutagenic nor genotoxic in vivo. In intact cells, a direct interaction of unlabelled and unmodified SAS with DNA was never found. Differences in the magnitude of biological responses between pyrogenic and precipitated silica described in some in vitro studies with murine macrophages at exaggerated exposure levels seem to be related to interactions with cell culture proteins and cell membranes. The in vivo studies do not indicate that there is a toxicologically relevant difference between SAS products after oral exposure. It is noted that any silicon dioxide product not meeting established specifications, and/or produced to provide new functionality in food, requires its own specific safety and risk assessment.
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Faust JJ, Doudrick K, Yang Y, Capco DG, Westerhoff P. A Facile Method for Separating and Enriching Nano and Submicron Particles from Titanium Dioxide Found in Food and Pharmaceutical Products. PLoS One 2016; 11:e0164712. [PMID: 27798677 PMCID: PMC5087857 DOI: 10.1371/journal.pone.0164712] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Accepted: 09/29/2016] [Indexed: 11/26/2022] Open
Abstract
Recent studies indicate the presence of nano-scale titanium dioxide (TiO2) as an additive in human foodstuffs, but a practical protocol to isolate and separate nano-fractions from soluble foodstuffs as a source of material remains elusive. As such, we developed a method for separating the nano and submicron fractions found in commercial-grade TiO2 (E171) and E171 extracted from soluble foodstuffs and pharmaceutical products (e.g., chewing gum, pain reliever, and allergy medicine). Primary particle analysis of commercial-grade E171 indicated that 54% of particles were nano-sized (i.e., < 100 nm). Isolation and primary particle analysis of five consumer goods intended to be ingested revealed differences in the percent of nano-sized particles from 32%‒58%. Separation and enrichment of nano- and submicron-sized particles from commercial-grade E171 and E171 isolated from foodstuffs and pharmaceuticals was accomplished using rate-zonal centrifugation. Commercial-grade E171 was separated into nano- and submicron-enriched fractions consisting of a nano:submicron fraction of approximately 0.45:1 and 3.2:1, respectively. E171 extracted from gum had nano:submicron fractions of 1.4:1 and 0.19:1 for nano- and submicron-enriched, respectively. We show a difference in particle adhesion to the cell surface, which was found to be dependent on particle size and epithelial orientation. Finally, we provide evidence that E171 particles are not immediately cytotoxic to the Caco-2 human intestinal epithelium model. These data suggest that this separation method is appropriate for studies interested in isolating the nano-sized particle fraction taken directly from consumer products, in order to study separately the effects of nano and submicron particles.
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Affiliation(s)
- James J. Faust
- Molecular and Cellular Biosciences, School of Life Sciences, Arizona State University, Tempe AZ 85287-4501, United States of America
| | - Kyle Doudrick
- Department of Civil and Environmental Engineering and Earth Sciences, 156 Fitzpatrick Hall, Notre Dame IN, 46556, United States of America
| | - Yu Yang
- School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe AZ 85287-5306, United States of America
| | - David G. Capco
- Molecular and Cellular Biosciences, School of Life Sciences, Arizona State University, Tempe AZ 85287-4501, United States of America
| | - Paul Westerhoff
- School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe AZ 85287-5306, United States of America
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