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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 21791

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Dr. Lorenzo Corsi

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Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
Interests: pharmacology; cancer; toxicology, neuroscience; phytotherapy; cell biology; molecular pharmacology
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Special Issue Information

Dear Colleagues,

The problem of environmental pollution is becoming a topic of debate in all areas of science. It is well known that such environmental contaminants are threatening human health. In this scenario, the presence of antibiotic residues and their metabolites in food intended for human and animal consumption may have a serious adverse effect, directly or indirectly. Indeed, some studies reveal that widespread antibiotic use in agriculture and aquaculture might contribute to the development of resistance to antibiotics commonly used in human medicine. In addition, a particular attention has been devoted to the potential toxicity of nanomaterials due to their rapid development in the last decade. Although a significant amount of scientific evidence has already described some of the potential impact of antibiotics and nanomaterials on human health, more knowledge is needed to investigate the toxicity of specific antibiotic residuals in food, and nanomaterials exposure as well. Particular attention will be devoted to papers describing studies of oxytetracycline (OTC) in food as well as the toxicity of metal nanoparticles (NPs), where the molecular mechanism, modulation of inflammatory pathways or cell transformation is reported. In vitro, in vivo, and human studies that contribute to the understanding of the potential impacts of these contaminants on human health are welcome.

Dr. Lorenzo Corsi
Guest Editor

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Keywords

nanoparticles
oxytetracycline
toxicology
inflammation
pollution
antibiotic resistance
cell toxicity
human health

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Published Papers (7 papers)

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Research

15 pages, 3177 KiB

Open AccessArticle

The Pro-Apoptotic Effect of Silica Nanoparticles Depends on Their Size and Dose, as Well as the Type of Glioblastoma Cells

by Rafał Krętowski, Magdalena Kusaczuk, Monika Naumowicz and Marzanna Cechowska-Pasko

Int. J. Mol. Sci. 2021, 22(7), 3564; https://doi.org/10.3390/ijms22073564 - 30 Mar 2021

Cited by 7 | Viewed by 2361

Abstract

Despite intensive investigations, nanoparticle-induced cellular damage is an important problem that has not been fully elucidated yet. Here, we report that silica nanoparticles (SiNPs) demonstrated anticancer influence on glioblastoma cells by the induction of apoptosis or necrosis. These effects are highly cell type-specific, as well as dependent on the size and dose of applied nanoparticles. Exposure of LN-18 and LBC3 cells to different sizes of SiNPs—7 nm, 5–15 nm, or 10–20 nm—at dosages, ranging from 12.5 to 1000 µg/mL, for 24 and 48 h reduced the viability of these cells. Treatment of LN-18 and LBC3 cells with 7 nm or 10–20 nm SiNPs at doses ≥50 µg/mL caused a strong induction of apoptosis, which is connected with an increase of intracellular reactive oxygen species (ROS) production. The 5–15 nm SiNPs exhibited distinct behavior comparing to silica nanoparticles of other studied sizes. In contrast to LBC3, in LN-18 cells exposed to 5–15 nm SiNPs we did not observe any effect on apoptosis. These nanoparticles exerted only strong necrosis, which was connected with a reduction in ROS generation. This suggests that SiNPs can trigger different cellular/molecular effects, depending on the exposure conditions, the size and dose of nanoparticles, and cell type of glioblastoma. Full article

(This article belongs to the Special Issue Toxicology of Metal NPs and OTC)

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26 pages, 4211 KiB

Open AccessArticle

Titanium Dioxide, but Not Zinc Oxide, Nanoparticles Cause Severe Transcriptomic Alterations in T98G Human Glioblastoma Cells

by Encarnación Fuster, Héctor Candela, Jorge Estévez, Eugenio Vilanova and Miguel A. Sogorb

Int. J. Mol. Sci. 2021, 22(4), 2084; https://doi.org/10.3390/ijms22042084 - 19 Feb 2021

Cited by 15 | Viewed by 3361

Abstract

Titanium dioxide and zinc oxide are two of the most widely used nanomaterials. We assessed the effects of noncytotoxic doses of both nanomaterials on T98G human glioblastoma cells by omic approaches. Surprisingly, no effects on the transcriptome of T98G cells was detected after exposure to 5 µg/mL of zinc oxide nanoparticles during 72 h. Conversely, the transcriptome of the cells exposed to 20 µg/mL of titanium dioxide nanoparticles during 72 h revealed alterations in lots of biological processes and molecular pathways. Alterations to the transcriptome suggests that exposure to titanium dioxide nanoparticles might, potentially, compromise the integrity of the blood brain barrier integrity and cause neuroinflammation. The latter issue was further confirmed phenotypically with a proteomic analysis and by recording the release of interleukin 8. Titanium dioxide also caused autophagy, which was demonstrated through the increase in the expression of the autophagy-related 3 and microtubule associated protein 1 light chain 3 alpha genes. The proteomic analysis revealed that titanium dioxide nanoparticles might have anticancerigen properties by downregulating genes involved in the detoxication of anthracyclines. A risk assessment resulting from titanium dioxide exposure, focusing on the central nervous system as a potential target of toxicity, is necessary. Full article

(This article belongs to the Special Issue Toxicology of Metal NPs and OTC)

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25 pages, 10107 KiB

Open AccessArticle

Time-Dependent Internalization of Polymer-Coated Silica Nanoparticles in Brain Endothelial Cells and Morphological and Functional Effects on the Blood-Brain Barrier

by Aniela Bittner, Fabien Gosselet, Emmanuel Sevin, Lucie Dehouck, Angélique D. Ducray, Véronique Gaschen, Michael H. Stoffel, Hansang Cho and Meike Mevissen

Int. J. Mol. Sci. 2021, 22(4), 1657; https://doi.org/10.3390/ijms22041657 - 6 Feb 2021

Cited by 4 | Viewed by 3483

Abstract

Nanoparticle (NP)-assisted procedures including laser tissue soldering (LTS) offer advantages compared to conventional microsuturing, especially in the brain. In this study, effects of polymer-coated silica NPs used in LTS were investigated in human brain endothelial cells (ECs) and blood-brain barrier models. In the co-culture setting with ECs and pericytes, only the cell type directly exposed to NPs displayed a time-dependent internalization. No transfer of NPs between the two cell types was observed. Cell viability was decreased relatively to NP exposure duration and concentration. Protein expression of the nuclear factor ĸ-light-chain-enhancer of activated B cells and various endothelial adhesion molecules indicated no initiation of inflammation or activation of ECs after NP exposure. Differentiation of CD34+ ECs into brain-like ECs co-cultured with pericytes, blood-brain barrier (BBB) characteristics were obtained. The established endothelial layer reduced the passage of integrity tracer molecules. NP exposure did not result in alterations of junctional proteins, BBB formation or its integrity. In a 3-dimensional setup with an endothelial tube formation and tight junctions, barrier formation was not disrupted by the NPs and NPs do not seem to cross the blood-brain barrier. Our findings suggest that these polymer-coated silica NPs do not damage the BBB. Full article

(This article belongs to the Special Issue Toxicology of Metal NPs and OTC)

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11 pages, 3123 KiB

Open AccessArticle

Size-Specific Copper Nanoparticle Cytotoxicity Varies between Human Cell Lines

by Ina Na and David C. Kennedy

Int. J. Mol. Sci. 2021, 22(4), 1548; https://doi.org/10.3390/ijms22041548 - 4 Feb 2021

Cited by 8 | Viewed by 2424

Abstract

Commercially available copper nanoparticles of three different sizes were tested for cytotoxicity against three human cell lines using four different cytotoxicity assays. This array of data was designed to elucidate trends in particle stability, uptake, and cytotoxicity. The copper nanoparticles are not stable in cell culture media, and rapid changes over the time course of the assays play a critical role in the measured endpoints. Typically, the 40–60 nm particles tested were more cytotoxic than either smaller or larger particles. These particles were also taken up more readily by cells and exhibited different stability dynamics in cell culture media. This provides a good correlation between total cellular uptake of copper and cytotoxicity that may be directly linked to particle stability, though it is unclear why the intermediate-sized particles exhibited these unique properties when compared with both larger and smaller particles. Full article

(This article belongs to the Special Issue Toxicology of Metal NPs and OTC)

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24 pages, 7475 KiB

Open AccessArticle

Environmentally Relevant Iron Oxide Nanoparticles Produce Limited Acute Pulmonary Effects in Rats at Realistic Exposure Levels

by Chang Guo, Ralf J. M. Weber, Alison Buckley, Julie Mazzolini, Sarah Robertson, Juana Maria Delgado-Saborit, Joshua Z. Rappoport, James Warren, Alan Hodgson, Paul Sanderson, James Kevin Chipman, Mark R. Viant and Rachel Smith

Int. J. Mol. Sci. 2021, 22(2), 556; https://doi.org/10.3390/ijms22020556 - 8 Jan 2021

Cited by 17 | Viewed by 3691

Abstract

Iron is typically the dominant metal in the ultrafine fraction of airborne particulate matter. Various studies have investigated the toxicity of inhaled nano-sized iron oxide particles (FeO_xNPs) but their results have been contradictory, with some indicating no or minor effects and others finding effects including oxidative stress and inflammation. Most studies, however, did not use materials reflecting the characteristics of FeO_xNPs present in the environment. We, therefore, analysed the potential toxicity of FeO_xNPs of different forms (Fe₃O₄, α-Fe₂O₃ and γ-Fe₂O₃) reflecting the characteristics of high iron content nano-sized particles sampled from the environment, both individually and in a mixture (FeO_x-mix). A preliminary in vitro study indicated Fe₃O₄ and FeO_x-mix were more cytotoxic than either form of Fe₂O₃ in human bronchial epithelial cells (BEAS-2B). Follow-up in vitro (0.003, 0.03, 0.3 µg/mL, 24 h) and in vivo (Sprague–Dawley rats, nose-only exposure, 50 µg/m³ and 500 µg/m³, 3 h/d × 3 d) studies therefore focused on these materials. Experiments in vitro explored responses at the molecular level via multi-omics analyses at concentrations below those at which significant cytotoxicity was evident to avoid detection of responses secondary to toxicity. Inhalation experiments used aerosol concentrations chosen to produce similar levels of particle deposition on the airway surface as were delivered in vitro. These were markedly higher than environmental concentrations. No clinical signs of toxicity were seen nor effects on BALF cell counts or LDH levels. There were also no significant changes in transcriptomic or metabolomic responses in lung or BEAS-2B cells to suggest adverse effects. Full article

(This article belongs to the Special Issue Toxicology of Metal NPs and OTC)

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20 pages, 5096 KiB

Open AccessArticle

Disruption of Cell Adhesion and Cytoskeletal Networks by Thiol-Functionalized Silica-Coated Iron Oxide Nanoparticles

by Karel Královec, Lucie Melounková, Marcela Slováková, Nikola Mannová, Miloš Sedlák, Jan Bartáček and Radim Havelek

Int. J. Mol. Sci. 2020, 21(24), 9350; https://doi.org/10.3390/ijms21249350 - 8 Dec 2020

Cited by 13 | Viewed by 3571

Abstract

One of the major obstacles that limits the use of magnetic nanoparticles in biomedical applications is their potential toxicity. In the present study, we evaluated the cytotoxic effects of thiol-functionalized silica-coated iron oxide (Fe₃O₄@SiO₂-SH) nanoparticles using human lung epithelial cells A549. We investigated the effect of Fe₃O₄@SiO₂-SH nanoparticles on the cell viability, proliferation, cell cycle distribution, adhesion, apoptosis, and the orientation of the cytoskeletal networks, as well as on expression of proteins involved in cell death, cell survival, and cell adhesion. We demonstrated that exposure of A549 cells to Fe₃O₄@SiO₂-SH nanoparticles resulted in severe disruption of the actin microfilaments and microtubule cytoskeleton and reduced the size of focal adhesions. Furthermore, cell adhesion was significantly affected as well as the phosphorylation of focal adhesion kinase (FAK), extracellular-signal-regulated kinase (ERK), and p38. Our findings highlight the need for in-depth cytotoxic evaluation of nanoparticles supporting their safer use, especially in biomedical applications. Full article

(This article belongs to the Special Issue Toxicology of Metal NPs and OTC)

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13 pages, 1654 KiB

Open AccessArticle

Evaluation of the Effects of Particle Sizes of Silver Nanoparticles on Various Biological Systems

by In Chul Kong, Kyung-Seok Ko and Dong-Chan Koh

Int. J. Mol. Sci. 2020, 21(22), 8465; https://doi.org/10.3390/ijms21228465 - 11 Nov 2020

Cited by 27 | Viewed by 2216

Abstract

Seven biological methods were adopted (three bacterial activities of bioluminescence, enzyme, enzyme biosynthetic, algal growth, seed germination, and root and shoot growth) to compare the toxic effects of two different sizes of silver nanoparticles (AgNPs). AgNPs showed a different sensitivity in each bioassay. Overall, the order of inhibitory effects was roughly observed as follows; bacterial bioluminescence activity ≈ root growth > biosynthetic activity of enzymes ≈ algal growth > seed germination ≈ enzymatic activity > shoot growth. For all bacterial activities (bioluminescence, enzyme, and enzyme biosynthesis), the small AgNPs showed statistically significantly higher toxicity than the large ones (p < 0.0036), while no significant differences were observed among other biological activities. The overall effects on the biological activities (except shoot growth) of the small AgNPs were shown to have about 4.3 times lower EC₅₀ (high toxicity) value than the large AgNPs. These results also indicated that the bacterial bioluminescence activity appeared to be an appropriate method among the tested ones in terms of both sensitivity and the discernment of particle sizes of AgNPs. Full article

(This article belongs to the Special Issue Toxicology of Metal NPs and OTC)

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