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Special Issue "Nanotoxicology and Nanosafety 2.0"

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: 29 February 2020.

Special Issue Editor

Prof. Dr. Ying-Jan Wang
E-Mail Website
Guest Editor
National Cheng Kung University | NCKU · Department of Environmental and Occupational Health
Interests: nanotoxicology; environmental toxicology; ecotoxicology; nanosafety; alternative testing methods; regulatory toxicology; adverse outcome pathways

Special Issue Information

Dear Colleagues,

With the rapid development of nanotechnology, nanomaterials have been widely applied in many industrial sectors, including medicine, consumer products, and electronics. While such technology has brought benefits and convenience into our daily lives, it may also potentially threaten human health and environmental safety. However, knowledge of the adverse health effects of these nanomaterials is still very limited. In this Special Issue, we hope to bring together significant research that advances the knowledge base on the adverse effects of nanomaterials, as well as the regulatory aspects of nanomaterials. In vitro, in vivo, and human studies that contribute to our understanding of human health and environmental impacts are welcome. Of particular interest will be papers that describe studies where modes of action and adverse outcome pathways could be evaluated during nanomaterials intoxication. In addition, alternative testing methods using zebrafish, drosophila, and C. Elegant are also welcome. This Special Issue will focus on the publication of original manuscripts and critical reviews to advance our understanding of the possible health effects of nanomaterials, as well as the means to protect workers and consumers exposed to them.

Prof. Dr. Ying-Jan Wang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • molecular and cellular mechanisms of nanomaterials intoxication
  • regulatory toxicology
  • nanotoxicology
  • nanosafety
  • alternative testing methods
  • ecotoxicity of nanomaterials
  • adverse effects of nanomaterials in zebrafish
  • adverse effects of nanomaterials in drosophila
  • adverse effects of nanomaterials in C. Elegant
  • risk assessment of engineered nanomaterials
  • risk management of engineered nanomaterials
  • biological monitoring of engineered nanomaterials
  • environmental monitoring of engineered nanomaterials

Related Special Issue

Published Papers (8 papers)

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Research

Open AccessArticle
Evaluation of the Genotoxic and Oxidative Damage Potential of Silver Nanoparticles in Human NCM460 and HCT116 Cells
Int. J. Mol. Sci. 2020, 21(5), 1618; https://doi.org/10.3390/ijms21051618 (registering DOI) - 27 Feb 2020
Abstract
Nano Ag has excellent antibacterial properties and is widely used in various antibacterial materials, such as antibacterial medicine and medical devices, food packaging materials and antibacterial textiles. Despite the many benefits of nano-Ag, more and more research indicates that it may have potential [...] Read more.
Nano Ag has excellent antibacterial properties and is widely used in various antibacterial materials, such as antibacterial medicine and medical devices, food packaging materials and antibacterial textiles. Despite the many benefits of nano-Ag, more and more research indicates that it may have potential biotoxic effects. Studies have shown that people who ingest nanoparticles by mouth have the highest uptake in the intestinal tract, and that the colon area is the most vulnerable to damage and causes the disease. In this study, we examined the toxic effects of different concentrations of Ag-NPs on normal human colon cells (NCM460) and human colon cancer cells (HCT116). As the concentration of nanoparticles increased, the activity of the two colon cells decreased and intracellular reactive oxygen species (ROS) increased. RT-qPCR and Western-blot analyses showed that Ag NPs can promote the increase in P38 protein phosphorylation levels in two colon cells and promote the expression of P53 and Bax. The analysis also showed that Ag NPs can promote the down-regulation of Bcl-2, leading to an increased Bax / Bcl-2 ratio and activation of P21, further accelerating cell death .This study showed that a low concentration of nano Ag has no obvious toxic effect on colon cells, while nano Ag with concentrations higher than 15 μg/mL will cause oxidative damage to colon cells. Full article
(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)
Open AccessArticle
Nanoplastics Cause Neurobehavioral Impairments, Reproductive and Oxidative Damages, and Biomarker Responses in Zebrafish: Throwing up Alarms of Wide Spread Health Risk of Exposure
Int. J. Mol. Sci. 2020, 21(4), 1410; https://doi.org/10.3390/ijms21041410 - 19 Feb 2020
Abstract
Plastic pollution is a growing global emergency and it could serve as a geological indicator of the Anthropocene era. Microplastics are potentially more hazardous than macroplastics, as the former can permeate biological membranes. The toxicity of microplastic exposure on humans and aquatic organisms [...] Read more.
Plastic pollution is a growing global emergency and it could serve as a geological indicator of the Anthropocene era. Microplastics are potentially more hazardous than macroplastics, as the former can permeate biological membranes. The toxicity of microplastic exposure on humans and aquatic organisms has been documented, but the toxicity and behavioral changes of nanoplastics (NPs) in mammals are scarce. In spite of their small size, nanoplastics have an enormous surface area, which bears the potential to bind even bigger amounts of toxic compounds in comparison to microplastics. Here, we used polystyrene nanoplastics (PS-NPs) (diameter size at ~70 nm) to investigate the neurobehavioral alterations, tissue distribution, accumulation, and specific health risk of nanoplastics in adult zebrafish. The results demonstrated that PS-NPs accumulated in gonads, intestine, liver, and brain with a tissue distribution pattern that was greatly dependent on the size and shape of the NPs particle. Importantly, an analysis of multiple behavior endpoints and different biochemical biomarkers evidenced that PS-NPs exposure induced disturbance of lipid and energy metabolism as well as oxidative stress and tissue accumulation. Pronounced behavior alterations in their locomotion activity, aggressiveness, shoal formation, and predator avoidance behavior were exhibited by the high concentration of the PS-NPs group, along with the dysregulated circadian rhythm locomotion activity after its chronic exposure. Moreover, several important neurotransmitter biomarkers for neurotoxicity investigation were significantly altered after one week of PS-NPs exposure and these significant changes may indicate the potential toxicity from PS-NPs exposure. In addition, after ~1-month incubation, the fluorescence spectroscopy results revealed the accumulation and distribution of PS-NPs across zebrafish tissues, especially in gonads, which would possibly further affect fish reproductive function. Overall, our results provided new evidence for the adverse consequences of PS-NPs-induced behavioral dysregulation and changes at the molecular level that eventually reduce the survival fitness of zebrafish in the ecosystem. Full article
(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)
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Open AccessArticle
The Vitamin A and D Exposure of Cells Affects the Intracellular Uptake of Aluminum Nanomaterials and Its Agglomeration Behavior: A Chemo-Analytic Investigation
Int. J. Mol. Sci. 2020, 21(4), 1278; https://doi.org/10.3390/ijms21041278 - 14 Feb 2020
Abstract
Aluminum (Al) is extensively used for the production of different consumer products, agents, as well as pharmaceuticals. Studies that demonstrate neurotoxicity and a possible link to Alzheimer’s disease trigger concern about potential health risks due to high Al intake. Al in cosmetic products [...] Read more.
Aluminum (Al) is extensively used for the production of different consumer products, agents, as well as pharmaceuticals. Studies that demonstrate neurotoxicity and a possible link to Alzheimer’s disease trigger concern about potential health risks due to high Al intake. Al in cosmetic products raises the question whether a possible interaction between Al and retinol (vitamin A) and cholecalciferol (vitamin D3) metabolism might exist. Understanding the uptake mechanisms of ionic or elemental Al and Al nanomaterials (Al NMs) in combination with bioactive substances are important for the assessment of possible health risk associated. Therefore, we studied the uptake and distribution of Al oxide (Al2O3) and metallic Al0 NMs in the human keratinocyte cell line HaCaT. Possible alterations of the metabolic pattern upon application of the two Al species together with vitamin A or D3 were investigated. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging and inductively coupled plasma mass spectrometry (ICP-MS) were applied to quantify the cellular uptake of Al NMs. Full article
(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)
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Open AccessArticle
Manifestation of Systemic Toxicity in Rats after a Short-Time Inhalation of Lead Oxide Nanoparticles
Int. J. Mol. Sci. 2020, 21(3), 690; https://doi.org/10.3390/ijms21030690 - 21 Jan 2020
Abstract
Outbred female rats were exposed to inhalation of lead oxide nanoparticle aerosol produced right then and there at a concentration of 1.30 ± 0.10 mg/m3 during 5 days for 4 h a day in a nose-only setup. A control group of rats [...] Read more.
Outbred female rats were exposed to inhalation of lead oxide nanoparticle aerosol produced right then and there at a concentration of 1.30 ± 0.10 mg/m3 during 5 days for 4 h a day in a nose-only setup. A control group of rats were sham-exposed in parallel under similar conditions. Even this short-time exposure of a relatively low level was associated with nanoparticles retention demonstrable by transmission electron microscopy in the lungs and the olfactory brain. Some impairments were found in the organism’s status in the exposed group, some of which might be considered lead-specific toxicological outcomes (in particular, increase in reticulocytes proportion, in δ-aminolevulinic acid (δ-ALA) urine excretion, and the arterial hypertension’s development). Full article
(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)
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Open AccessArticle
Fate Determination of ZnO in Commercial Foods and Human Intestinal Cells
Int. J. Mol. Sci. 2020, 21(2), 433; https://doi.org/10.3390/ijms21020433 - 09 Jan 2020
Abstract
(1) Background: Zinc oxide (ZnO) particles are widely used as zinc (Zn) fortifiers, because Zn is essential for various cellular functions. Nanotechnology developments may lead to production of nano-sized ZnO, although nanoparticles (NPs) are not intended to be used as food additives. Current [...] Read more.
(1) Background: Zinc oxide (ZnO) particles are widely used as zinc (Zn) fortifiers, because Zn is essential for various cellular functions. Nanotechnology developments may lead to production of nano-sized ZnO, although nanoparticles (NPs) are not intended to be used as food additives. Current regulations do not specify the size distribution of NPs. Moreover, ZnO is easily dissolved into Zn ions under acidic conditions. However, the fate of ZnO in commercial foods or during intestinal transit is still poorly understood. (2) Methods: We established surfactant-based cloud point extraction (CPE) for ZnO NP detection as intact particle forms using pristine ZnO-NP-spiked powdered or liquid foods. The fate determination and dissolution characterization of ZnO were carried out in commercial foods and human intestinal cells using in vitro intestinal transport and ex vivo small intestine absorption models. (3) Results: The results demonstrated that the CPE can effectively separate ZnO particles and Zn ions in food matrices and cells. The major fate of ZnO in powdered foods was in particle form, in contrast to its ionic fate in liquid beverages. The fate of ZnO was closely related to the extent of its dissolution in food or biomatrices. ZnO NPs were internalized into cells in both particle and ion form, but dissolved into ions with time, probably forming a Zn–ligand complex. ZnO was transported through intestinal barriers and absorbed in the small intestine primarily as Zn ions, but a small amount of ZnO was absorbed as particles. (4) Conclusion: The fate of ZnO is highly dependent on food matrix type, showing particle and ionic fates in powdered foods and liquid beverages, respectively. The major intracellular and intestinal absorption fates of ZnO NPs were Zn ions, but a small portion of ZnO particle fate was also observed after intestinal transit. These findings suggest that the toxicity of ZnO is mainly related to the Zn ion, but potential toxicity resulting from ZnO particles cannot be completely excluded. Full article
(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)
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Open AccessArticle
Neuron-Like Cells Generated from Human Umbilical Cord Lining-Derived Mesenchymal Stem Cells as a New In Vitro Model for Neuronal Toxicity Screening: Using Magnetite Nanoparticles as an Example
Int. J. Mol. Sci. 2020, 21(1), 271; https://doi.org/10.3390/ijms21010271 - 31 Dec 2019
Abstract
The wide employment of iron nanoparticles in environmental and occupational settings underlines their potential to enter the brain. Human cell-based systems are recommended as relevant models to reduce uncertainty and to improve prediction of human toxicity. This study aimed at demonstrating the in [...] Read more.
The wide employment of iron nanoparticles in environmental and occupational settings underlines their potential to enter the brain. Human cell-based systems are recommended as relevant models to reduce uncertainty and to improve prediction of human toxicity. This study aimed at demonstrating the in vitro differentiation of the human umbilical cord lining-derived-mesenchymal stem cells (hCL-MSCs) into neuron-like cells (hNLCs) and the benefit of using them as an ideal primary cell source of human origin for the neuronal toxicity of Fe3O4NPs (magnetite-nanoparticles). Neuron-like phenotype was confirmed by: live morphology; Nissl body staining; protein expression of different neuronal-specific markers (immunofluorescent staining), at different maturation stages (i.e., day-3-early and day-8-full differentiated), namely β-tubulin III, MAP-2, enolase (NSE), glial protein, and almost no nestin and SOX-2 expression. Synaptic makers (SYN, GAP43, and PSD95) were also expressed. Fe3O4NPs determined a concentration- and time-dependent reduction of hNLCs viability (by ATP and the Trypan Blue test). Cell density decreased (20–50%) and apoptotic effects were detected at ≥10 μg/mL in both types of differentiated hNLCs. Three-day-differentiated hNLCs were more susceptible (toxicity appeared early and lasted for up to 48 h) than 8-day-differentiated cells (delayed effects). The study demonstrated that (i) hCL-MSCs easily differentiated into neuronal-like cells; (ii) the hNCLs susceptibility to Fe3O4NPs; and (iii) human primary cultures of neurons are new in vitro model for NP evaluation. Full article
(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)
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Open AccessArticle
Behavioral Impairments and Oxidative Stress in the Brain, Muscle, and Gill Caused by Chronic Exposure of C70 Nanoparticles on Adult Zebrafish
Int. J. Mol. Sci. 2019, 20(22), 5795; https://doi.org/10.3390/ijms20225795 - 18 Nov 2019
Abstract
There is an imperative need to develop efficient whole-animal-based testing assays to determine the potential toxicity of engineered nanomaterials. While previous studies have demonstrated toxicity in lung and skin cells after C70 nanoparticles (NPs) exposure, the potential detrimental role of C70 [...] Read more.
There is an imperative need to develop efficient whole-animal-based testing assays to determine the potential toxicity of engineered nanomaterials. While previous studies have demonstrated toxicity in lung and skin cells after C70 nanoparticles (NPs) exposure, the potential detrimental role of C70 NPs in neurobehavior is largely unaddressed. Here, we evaluated the chronic effects of C70 NPs exposure on behavior and alterations in biochemical responses in adult zebrafish. Two different exposure doses were used for this experiment: low dose (0.5 ppm) and high dose (1.5 ppm). Behavioral tests were performed after two weeks of exposure of C70 NPs. We found decreased locomotion, exploration, mirror biting, social interaction, and shoaling activities, as well as anxiety elevation and circadian rhythm locomotor activity impairment after ~2 weeks in the C70 NP-exposed fish. The results of biochemical assays reveal that following exposure of zebrafish to 1.5 ppm of C70 NPs, the activity of superoxide dismutase (SOD) in the brain and muscle tissues increased significantly. In addition, the concentration of reactive oxygen species (ROS) also increased from 2.95 ± 0.12 U/ug to 8.46 ± 0.25 U/ug and from 0.90 ± 0.03 U/ug to 3.53 ± 0.64 U/ug in the muscle and brain tissues, respectively. Furthermore, an increased level of cortisol was also observed in muscle and brain tissues, ranging from 17.95 ± 0.90 pg/ug to 23.95 ± 0.66 pg/ug and from 3.47 ± 0.13 pg/ug to 4.91 ± 0.51 pg/ug, respectively. Increment of Hif1-α level was also observed in both tissues. The elevation was ranging from 11.65 ± 0.54 pg/ug to 18.45 ± 1.00 pg/ug in the muscle tissue and from 4.26 ± 0.11 pg/ug to 6.86 ± 0.37 pg/ug in the brain tissue. Moreover, the content of DNA damage and inflammatory markers such as ssDNA, TNF-α, and IL-1β were also increased substantially in the brain tissues. Significant changes in several biomarker levels, including catalase and malondialdehyde (MDA), were also observed in the gill tissues. Finally, we used a neurophenomic approach with a particular focus on environmental influences, which can also be easily adapted for other aquatic fish species, to assess the toxicity of metal and carbon-based nanoparticles. In summary, this is the first study to illustrate the adult zebrafish toxicity and the alterations in several neurobehavior parameters after zebrafish exposure to environmentally relevant amounts of C70 NPs. Full article
(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)
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Open AccessArticle
Role of Autophagy in Zinc Oxide Nanoparticles-Induced Apoptosis of Mouse LEYDIG Cells
Int. J. Mol. Sci. 2019, 20(16), 4042; https://doi.org/10.3390/ijms20164042 - 19 Aug 2019
Cited by 1
Abstract
Zinc oxide nanoparticles (ZnO NPs) have shown adverse health impact on the human male reproductive system, with evidence of inducing apoptosis. However, whether or not ZnO NPs could promote autophagy, and the possible role of autophagy in the progress of apoptosis, remain unclear. [...] Read more.
Zinc oxide nanoparticles (ZnO NPs) have shown adverse health impact on the human male reproductive system, with evidence of inducing apoptosis. However, whether or not ZnO NPs could promote autophagy, and the possible role of autophagy in the progress of apoptosis, remain unclear. In the current study, in vitro and in vivo toxicological responses of ZnO NPs were explored by using a mouse model and mouse Leydig cell line. It was found that intragastrical exposure of ZnO NPs to mice for 28 days at the concentrations of 100, 200, and 400 mg/kg/day disrupted the seminiferous epithelium of the testis and decreased the sperm density in the epididymis. Furthermore, serum testosterone levels were markedly reduced. The induction of apoptosis and autophagy in the testis tissues was disclosed by up-regulating the protein levels of cleaved Caspase-8, cleaved Caspase-3, Bax, LC3-II, Atg 5, and Beclin 1, accompanied by down-regulation of Bcl 2. In vitro tests showed that ZnO NPs could induce apoptosis and autophagy with the generation of oxidative stress. Specific inhibition of autophagy pathway significantly decreased the cell viability and up-regulated the apoptosis level in mouse Leydig TM3 cells. In summary, ZnO NPs can induce apoptosis and autophagy via oxidative stress, and autophagy might play a protective role in ZnO NPs-induced apoptosis of mouse Leydig cells. Full article
(This article belongs to the Special Issue Nanotoxicology and Nanosafety 2.0)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Magnetic nanoparticles toxicity on larvae and adult fish.

Nemi Malhotra 1, Tzong-Rong Ger 1 * and Chung-Der Hsiao 2,3,4 *

  1. Department of Biomedical Engineering, Chung Yuan Christian University, Chung-Li 32023, Taiwan
  2. Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan
  3. Department of Chemistry, Chung Yuan Christian University, Chung-Li 32023, Taiwan
  4. Center for Nanotechnology, Chung Yuan Christian University, Chung-Li 32023, Taiwan

* Correspondence to Tzong-Rong Ger ([email protected]); Chung-Der Hsiao ([email protected])

Abstract

The noteworthy intensification in development of nanotechnology, has led to development of various nanoparticles. The diverse applications of these nanoparticles make them desirable candidate for areas such as drug delivery, cosmetics, medicine, electronics, contrast agents for MRI and so on. Magnetic nanoparticles are a branch of nanoparticle’s which is specifically being considered as a contrast agent for MRI as well as targeted drug delivery vehicles. Besides the mentioned advantages, the toxicity of these magnetic nanoparticles is still less explored. Some nanoparticles have demonstrated the toxic effect on plants, cell lines as well as animal models, such as causing inflammation, ulceration, decrease in growth rate and decline in viability. The cause of nanoparticles toxicity is attributed to its specific characteristics of greater surface to volume ratio, surface coatings, size, dosage, retention in body, breakdown and elimination from body. In the current review paper, we therefore aim to sum up the toxicity effect of different magnetic nanoparticles on fish embryo/larvae and adults. As an important vertebrate model for assessing the effect of drugs fish has gained tremendous popularity. Also, the characteristic features of short reproductive cycle, transparency for visual assessment of developing organs and ease of maintenance make fish a good model for toxicity valuation. Therefore, we believe attaining a profound knowledge on the background of the subject we might get some insights on the field to give research in this field a new sustainable direction.

---------------------------------

Nano-plastics Cause Neurobehavioral Impairments, Oxidative Damage and Biomarker Response in Zebrafish: Throwing up Alarms of Wide Spread Health Risk of Exposure

Sreeja Sarasamma 1,2 #, Gilbert Audira 1,2 #, Petrus Siregar 2, Yu-Heng Lai 3, Sung-Tzu Liang 2, Jung-Ren Chen 4 * and Chung-Der Hsiao 1,2,4,5 *

  1. Department of Chemistry, Chung Yuan Christian University, Chung-Li, 32023, Taiwan
  2. Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, 32023, Taiwan
  3. Department of Biological Science & Technology, College of Medicine, I-Shou University, Kaohsiung, 82445, Taiwan
  4. Department of Chemistry, Chinese Culture university, Taipei, 11114, Taiwan
  5. Center for Nanotechnology, Chung Yuan Christian University, Chung-Li, 32023, Taiwan

Corresponding: Jung-Ren Chen ([email protected]); Department of Biological Science & Technology, College of Medicine, I-Shou University, Kaohsiung, 82445, Taiwan; Chung-Der Hsiao ([email protected]); Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, 32023, Taiwan

 

Abstract

BACKGROUND: Plastic pollution is a growing global emergency and it could serve as a geological indicator of the Anthropocene era. Micro-plastics are potentially more hazardous than macro-plastics as the former can permeate biological membranes.

OBJECTIVE: Toxicity of micro-plastic exposure on humans and aquatic organisms has been documented, but the toxicity and behavioral changes of nano-plastics in mammals is scarce. Despite their small size nano-plastics have an enormous surface area, bearing the potential to bind an even bigger amounts of toxic compounds than micro-plastics.

METHODS: Here we used polystyrene (PS) nano-plastics (diameter size at ~70nm) to investigate the neurobehavioral alterations, tissue distribution, accumulation and specific health risk of nano-plastics (NPs) in adult zebrafish.

RESULTS: Results demonstrated that NPs accumulated in gonads, intestine, liver and brain with a tissue distribution pattern greatly dependent on the size and shape of the NPs particle. Importantly, analysis of multiple behavior endpoints, different biochemical biomarkers and histology evidenced that NPs exposure induced disturbance of lipid and energy metabolism as well as oxidative stress and tissue accumulation. Moreover, neurotransmitter biomarkers of neurotoxicity were significantly altered after one week of NPs exposure.

CONCLUSION: Our results revealed the accumulation and distribution of NPs across zebrafish tissues and demonstrated significant changes in several biomarkers that indicate potential toxicity from NPs exposure. Overall, our results provided new evidence for the adverse consequences of NPs-induced behavioral dysregulation and changes at the molecular level that eventually reduce the survival fitness of zebrafish in the ecosystem.

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