The Role of Polymeric Coatings for a Safe-by-Design Development of Biomedical Gold Nanoparticles Assessed in Zebrafish Embryo

In the biomedical field, gold nanoparticles (GNPs) have attracted the attention of the scientific community thanks to their high potential in both diagnostic and therapeutic applications. The extensive use of GNPs led researchers to investigate their toxicity, identifying stability, size, shape, and surface charge as key properties determining their impact on biological systems, with possible strategies defined to reduce it according to a Safe-by-Design (SbD) approach. The purpose of the present work was to analyze the toxicity of GNPs of various sizes and with different coating polymers on the developing vertebrate model, zebrafish. In particular, increasing concentrations (from 0.001 to 1 nM) of 6 or 15 nm poly-(isobutylene-alt-maleic anhydride)-graft-dodecyl polymer (PMA)- or polyethylene glycol (PEG)-coated GNPs were tested on zebrafish embryos using the fish embryo test (FET). While GNP@PMA did not exert significant toxicity on zebrafish embryos, GNP@PEG induced a significant inhibition of embryo viability, a delay of hatching (with the smaller size NPs), and a higher incidence of malformations, in terms of tail morphology and eye development. Transmission electron microscope analysis evidenced that the more negatively charged GNP@PMA was sequestered by the positive charges of chorion proteins, with a consequent reduction in the amount of NPs able to reach the developing embryo and exert toxicological activity. The mild toxic response observed on embryos directly exposed to GNP@PMA suggest that these NPs are promising in terms of SbD development of gold-based biomedical nanodevices. On the other hand, the almost neutral GNP@PEG, which did not interact with the chorion surface and was free to cross chorion pores, significantly impacted the developing zebrafish. The present study raises concerns about the safety of PEGylated gold nanoparticles and contributes to the debated issue of the free use of this nanotool in medicine and nano-biotechnologies.

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Safe-by-Design CuO Nanoparticles via Fe-Doping, Cu–O Bond Length Variation, and Biological Assessment in Cells and Zebrafish Embryos

ACS Nano ◽

10.1021/acsnano.6b06495 ◽

2017 ◽

Vol 11 (1) ◽

pp. 501-515 ◽

Cited By ~ 49

Author(s):

Hendrik Naatz ◽

Sijie Lin ◽

Ruibin Li ◽

Wen Jiang ◽

Zhaoxia Ji ◽

...

Keyword(s):

Bond Length ◽

Cuo Nanoparticles ◽

Biological Assessment ◽

Zebrafish Embryos ◽

Length Variation ◽

Fe Doping ◽

Safe By Design ◽

In Cells

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Neurotoxic effects in zebrafish embryos by valproic acid and nine of its analogues: the fish-mouse connection?

Archives of Toxicology ◽

10.1007/s00204-020-02928-7 ◽

2020 ◽

Author(s):

Katharina Brotzmann ◽

André Wolterbeek ◽

Dinant Kroese ◽

Thomas Braunbeck

Keyword(s):

Valproic Acid ◽

Predictive Power ◽

In Vivo Studies ◽

In Vivo Model ◽

Zebrafish Embryos ◽

Fish Embryo ◽

Modes Of Action ◽

Detailed Assessment ◽

Mammalian Toxicity

Abstract Since teratogenicity testing in mammals is a particular challenge from an animal welfare perspective, there is a great need for the development of alternative test systems. In this context, the zebrafish (Danio rerio) embryo has received increasing attention as a non-protected embryonic vertebrate in vivo model. The predictive power of zebrafish embryos for general vertebrate teratogenicity strongly depends on the correlation between fish and mammals with respect to both overall general toxicity and more specific endpoints indicative of certain modes-of-action. The present study was designed to analyze the correlation between (1) effects of valproic acid and nine of its analogues in zebrafish embryos and (2) their known neurodevelopmental effects in mice. To this end, zebrafish embryos exposed for 120 h in an extended version of the acute fish embryo toxicity test (FET; OECD TG 236) were analyzed with respect to an extended list of sublethal endpoints. Particular care was given to endpoints putatively related to neurodevelopmental toxicity, namely jitter/tremor, deformation of sensory organs (eyes) and craniofacial deformation, which might correlate to neural tube defects caused by valproic acid in mammals. A standard evaluation of lethal (LC according to OECD TG 236) and sublethal toxicity (EC) merely indicated that four out of ten compounds tested in zebrafish correlate with positive results in mouse in vivo studies. A detailed assessment of more specific effects, however, namely, jitter/tremor, small eyes and craniofacial deformation, resulted in a correspondence of 75% with in vivo mouse data. A refinement of endpoint analysis from an integration of all observations into one LCx or ECx data (as foreseen by current ecotoxicology-driven OECD guidelines) to a differential evaluation of endpoints specific of selected modes-of-action thus increases significantly the predictive power of the zebrafish embryo model for mammalian teratogenicity. However, for some of the endpoints observed, e.g., scoliosis, lordosis, pectoral fin deformation and lack of movement, further experiments are required for the identification of underlying modes-of-action and an unambiguous interpretation of their predictive power for mammalian toxicity.

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Phenolic Profile of Herbal Infusion and Polyphenol-Rich Extract from Leaves of the Medicinal Plant Antirhea borbonica: Toxicity Assay Determination in Zebrafish Embryos and Larvae

Molecules ◽

10.3390/molecules25194482 ◽

2020 ◽

Vol 25 (19) ◽

pp. 4482

Author(s):

Bryan Veeren ◽

Batoul Ghaddar ◽

Matthieu Bringart ◽

Shaymaa Khazaal ◽

Marie-Paule Gonthier ◽

...

Keyword(s):

Antioxidant Properties ◽

Spinal Curvature ◽

Therapeutic Effects ◽

Zebrafish Embryos ◽

Endemic Plant ◽

Fish Embryo ◽

Liquid Chromatography Tandem Mass ◽

Pericardial Edema ◽

Living Organisms

Antirhea borbonica (A. borbonica) is an endemic plant from the Mascarene archipelago in the Indian Ocean commonly used in traditional medicine for its health benefits. This study aims (1) at exploring polyphenols profiles from two types of extracts—aqueous (herbal infusion) and acetonic (polyphenol rich) extracts from A. borbonica leaves—and (2) at evaluating their potential toxicity in vivo for the first time. We first demonstrated that, whatever type of extraction is used, both extracts displayed significant antioxidant properties and acid phenolic and flavonoid contents. By using selective liquid chromatography–tandem mass spectrometry, we performed polyphenol identification and quantification. Among the 19 identified polyphenols, we reported that the main ones were caffeic acid derivatives and quercetin-3-O-rutinoside. Then, we performed a Fish Embryo Acute Toxicity test to assess the toxicity of both extracts following the Organisation for Economic Cooperation and Development (OECD) guidelines. In both zebrafish embryos and larvae, the polyphenols-rich extract obtained by acetonic extraction followed by evaporation and resuspension in water exhibits a higher toxic effect with a median lethal concentration (LC50: 5.6 g/L) compared to the aqueous extract (LC50: 20.3 g/L). Our data also reveal that at non-lethal concentrations of 2.3 and 7.2 g/L for the polyphenol-rich extract and herbal infusion, respectively, morphological malformations such as spinal curvature, pericardial edema, and developmental delay may occur. In conclusion, our study strongly suggests that the evaluation of the toxicity of medicinal plants should be systematically carried out and considered when studying therapeutic effects on living organisms.

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Teratogenic potential of traditional Malaysian vegetables (ulam) in the zebrafish model

British Food Journal ◽

10.1108/bfj-02-2020-0118 ◽

2020 ◽

Vol 122 (10) ◽

pp. 3089-3098

Author(s):

Alya Hanisah Omar ◽

Chin Siang Kue ◽

Roza Dianita ◽

Ke-Xin Yu

Keyword(s):

Local Community ◽

Lethal Effect ◽

Negative Control ◽

Teratogenic Effect ◽

Zebrafish Embryos ◽

Zebrafish Model ◽

Fish Embryo ◽

Content Type ◽

Cancer Pathways ◽

Teratogenic Potential

PurposeTraditional Malaysian vegetables, also known as ulam, are believed to have healing properties among the local community. Ulam is commonly reported to have high antioxidant content which makes it a popular food. The purpose of this paper is to determine the teratogenic potential of eight ulam, using zebrafish model. The tested ulam were Cosmos caudatus, Gynura procumbens, Labisia pumila var. alata, Phaleria macrocarpa, Polygonum minus, Piper sarmentosum, Premna foetida and Sauropus androgynous.Design/methodology/approachMethanol extract of ulam was prepared using the maceration method. Various concentrations of extracts were tested against fish embryo short-term toxicity test. The lethal concentration (LC50) and teratogenic effect of the ulam were determined.FindingsAmong all tested species, L. pumila, P. foetida and S. androgynous showed 100% lethal effect towards zebrafish embryos at concentrations of 10 µg/mL, 1,000 µg/mL and 100 µg/mL, respectively. The three ulam have exhibited teratogenic effect on zebrafish embryos after 72 h post-fertilization. L. pumila had induced yolk sac edema at 1.0 µg/mL for normalized measurement of 108.3 ± 2.0% (which is higher than negative control, p < 0.05, median = 110.7%), while P. foetida had induced pericardial edema at 100 µg/mL for normalized measurement of 124.0 ± 4.6% (which is higher than negative control, p < 0.05, median = 124.3%). On the other hand, S. androgynus induced curve trunk at 30 µg/mL for the presence of 70.9 ± 4.2%.Originality/valueThe teratogenic effect of L. pumila, P. foetida and S. androgynous suggests the possible disruption in the embryogenesis in zebrafish, namely Notch, vascular endothelial growth factor (VEGF) and retinoic acid pathways. The results of ulam gave possible implications and insights on the cancer pathways involved, which could be a useful target for cancer research. This is the first report on teratogenicity evaluation of Malaysian ulam showing relationship to cancer pathways by using zebrafish embryo model.

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Comparative toxicity assessment of in situ burn residues to initial and dispersed heavy fuel oil using zebrafish embryos as test organisms

Environmental Science and Pollution Research ◽

10.1007/s11356-020-11729-5 ◽

2020 ◽

Author(s):

Sarah Johann ◽

Mira Goßen ◽

Leonie Mueller ◽

Valentina Selja ◽

Kim Gustavson ◽

...

Keyword(s):

Scientific Information ◽

Fuel Oil ◽

Zebrafish Embryos ◽

Life Stages ◽

Biological Organization ◽

Heavy Fuel Oil ◽

Toxic Response ◽

Chemical Dispersant ◽

The Impact

AbstractIn situ burning (ISB) is discussed to be one of the most suitable response strategies to combat oil spills in extreme conditions. After burning, a highly viscous and sticky residue is left and may over time pose a risk of exposing aquatic biota to toxic oil compounds. Scientific information about the impact of burn residues on the environment is scarce. In this context, a comprehensive ISB field experiment with approx. 1000L IFO 180 was conducted in a fjord in Greenland. The present study investigated the toxicity of collected ISB residues to early life stages of zebrafish (Danio rerio) as a model for potentially exposed pelagic organisms. The toxicity of ISB residues on zebrafish embryos was compared with the toxicity of the initial (unweathered) IFO 180 and chemically dispersed IFO 180. Morphological malformations, hatching success, swimming behavior, and biomarkers for exposure (CYP1A activity, AChE inhibition) were evaluated in order to cover the toxic response on different biological organization levels. Across all endpoints, ISB residues did not induce greater toxicity in zebrafish embryos compared with the initial oil. The application of a chemical dispersant increased the acute toxicity most likely due to a higher bioavailability of dissolved and particulate oil components. The results provide insight into the adverse effects of ISB residues on sensitive life stages of fish in comparison with chemical dispersant application.

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Toxicity assessment of precise engineered gold nanoparticles with different shapes in zebrafish embryos

RSC Advances ◽

10.1039/c6ra00632a ◽

2016 ◽

Vol 6 (39) ◽

pp. 33009-33013 ◽

Cited By ~ 11

Author(s):

Zhenjie Wang ◽

Dan Xie ◽

Hongzhuo Liu ◽

Zhihong Bao ◽

Yongjun Wang

Keyword(s):

Gold Nanoparticles ◽

Developmental Toxicity ◽

Toxicity Assessment ◽

Zebrafish Embryos ◽

Zebrafish Model ◽

Different Shapes

The developmental toxicity of gold nanoparticles with different shape in a zebrafish model was investigated and compared.

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Effects of increasing water temperature and decreasing water oxygen concentration on enzyme activity in developing carp embryos (Cyprinus carpio)

Fisheries & Aquatic Life ◽

10.2478/aopf-2021-0004 ◽

2021 ◽

Vol 29 (1) ◽

pp. 35-44

Author(s):

Oleksandr M. Vodianitskyi ◽

Oleksandr S. Potrokhov ◽

Oleg G. Zinkovskyi ◽

Yurii M. Khudiiash ◽

Mykola V. Prychepa

Keyword(s):

Climate Change ◽

Enzyme Activity ◽

Lactate Dehydrogenase ◽

Water Temperature ◽

Aerobic Respiration ◽

Embryo Viability ◽

Fish Embryo ◽

Ldh Activity ◽

Water Oxygen ◽

Fish Spawning

Abstract Climate change inevitably leads to increased water temperatures, which is especially important in natural spawning grounds during mass fish spawning. Studies were performed to determine the effects of increased water temperature with decreased water oxygen concentrations on the activity of Na+/K+ ATPase, lactate dehydrogenase (LDH), and succinate dehydrogenase in developing carp embryos. The activities of ATP and LDH decreased several times when water temperature increased from 24 to 31°C. LDH activity increased up to 1.9 times. Thus, the fish embryos used glycolysis to a greater extent, the level of their aerobic respiration decreased, and mineral exchange with the environment was weakened. These phenomena could have disrupted embryonic development and decreased fish embryo viability.

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Sensitivity of Zebrafish (Danio rerio) Embryos to Hospital Effluent Compared to Daphnia magna and Aliivibrio fischeri

Physiological Research ◽

10.33549/physiolres.934616 ◽

2020 ◽

pp. S681-S691

Author(s):

M WITTLEROVÁ ◽

G JÍROVÁ ◽

A VLKOVÁ ◽

K KEJLOVÁ ◽

M MALÝ ◽

...

Keyword(s):

Acute Toxicity ◽

Daphnia Magna ◽

Sublethal Effects ◽

Aquatic Organisms ◽

Spinal Curvature ◽

Treated Wastewater ◽

Zebrafish Embryos ◽

Fish Embryo ◽

Additional Tool ◽

Aliivibrio Fischeri

The Fish Embryo Acute Toxicity (FET) Test was adopted by the Organisation for Economic Co-operation and Development as OECD TG 236 in 2013. The test has been designed to determine acute toxicity of chemicals on embryonic stages of fish and proposed as an alternative method to the Fish Acute Toxicity Test performed according to OECD TG 203. In recent years fish embryos were used not only in the assessment of toxicity of chemicals but also for environmental and wastewater samples. In our study we investigated the acute toxicity of treated wastewater from seven hospitals in the Czech Republic. Our main purpose was to compare the suitability and sensitivity of zebrafish embryos with the sensitivity of two other aquatic organisms commonly used for wastewater testing – Daphnia magna and Aliivibrio fischeri. For the aim of this study, in addition to the lethal endpoints of the FET test, sublethal effects such as delayed heartbeat, lack of blood circulation, pericardial and yolk sac edema, spinal curvature and pigmentation failures were evaluated. The comparison of three species demonstrated that the sensitivity of zebrafish embryos is comparable or in some cases higher than the sensitivity of D. magna and A. fischeri. The inclusion of sublethal endpoints caused statistically significant increase of the FET test efficiency in the range of 1-12 %. Based on our results, the FET test, especially with the addition of sublethal effects evaluation, can be considered as a sufficiently sensitive and useful additional tool for ecotoxicity testing of the acute toxicity potential of hospital effluents.

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