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The contamination of water by arsenic (As) has emerged as a significant environmental concern due to its well-documented toxicity. Environmentally relevant concentrations of As have been reported to pose a considerable threat to fish. However, previous studies mainly focused on the impacts of As at environmentally relevant concentrations on adult fish, and limited information is available regarding its impacts on fish at early life stage. In this study, zebrafish embryos were employed to evaluate the environmental risks following exposure to different concentrations (0, 25, 50, 75 and 150 μg/L) of pentavalent arsenate (AsV) for 120 hours post fertilization. Our findings indicated that concentrations ≤ 150 μg/L AsV did not exert significant effects on survival or aberration; however, it conspicuously inhibited heart rate of zebrafish larvae. Furthermore, exposure to AsV significantly disrupted mRNA transcription of genes associated with cardiac development, and elongated the distance between the sinus venosus and bulbus arteriosus at 75 μg/L and 150 μg/L treatments. Additionally, AsV exposure enhanced superoxide dismutase (SOD) activity at 50, 75 and 150 μg/L treatments, and increased mRNA transcriptional levels of Cu/ZnSOD and MnSOD at 75 and 150 μg/L treatments. Concurrently, AsV suppressed metallothionein1 (MT1) and MT2 mRNA transcriptions while elevating heat shock protein70 mRNA transcription levels in zebrafish larvae resulting in elevated malondialdehyde (MDA) levels. These findings provide novel insights into the toxic effects exerted by low concentrations of AsV on fish at early life stage, thereby contributing to an exploration into the environmental risks associated with environmentally relevant concentrations. [Display omitted] • ≤ 150 μg/L AsV had no significant effect on survival and aberration rates of zebrafish larvae. • ≥ 25 μg/L AsV inhibited heart rate of zebrafish embryo. • ≥ 75 μg/L AsV delayed cardiac development of zebrafish larvae. • ≥ 25 μg/L AsV caused oxidative stress and oxidative damage. [ABSTRACT FROM AUTHOR]

Strobilurins, among the most used fungicides worldwide, are considered non-toxic to mammals and birds, but there is growing evidence that these compounds are highly toxic to aquatic species. Dimoxystrobin has been included in the 3rd Watch List of the European Commission, and it has been classified as very toxic to aquatic life. However, previous studies focused on acute toxicity and only two reports are available on its impact on fish, and none on its effects during the early life stages. Here, we evaluated for the first time the effects induced on zebrafish embryos and larvae by two dimoxystrobin sublethal concentrations (6.56 and 13.13 μg/L) falling in the range of predicted environmental concentrations. We demonstrated that short-term exposure to dimoxystrobin may exert adverse effects on multiple targets, inducing severe morphological alterations. Moreover, we showed enhanced mRNA levels of genes related to the mitochondrial respiratory chain and ATP production. Impairment of the swim bladder inflation has also been recorded, which may be related to the observed swimming performance alterations. [Display omitted] • Dimoxystrobin induces morphological alterations in zebrafish embryos and larvae • The severity of injuries increases with increasing time and dose of exposure • Dimoxystrobin enhances mRNA level of genes related to the mitochondrial respiration • Swim bladder impairment may be related to swimming performance [ABSTRACT FROM AUTHOR]

The available information regarding the impact of antimony (Sb), a novel environmental pollutant, on the intestinal microbiota and host health is limited. In this study, we conducted physiological characterizations to investigate the response of adult zebrafish to different environmental concentrations (0, 30, 300, and 3000 µg/L) of Sb over a period of 14 days. Biochemical and pathological changes demonstrated that Sb effectively compromised the integrity of the intestinal physical barrier and induced inflammatory responses as well as oxidative stress. Analysis of both intestinal microbial community and metabolome revealed that exposure to 0 and 30 µg/L of Sb resulted in similar microbiota structures; however, exposure to 300 µg/L altered microbial communities' composition (e.g., a decline in genus Cetobacterium and an increase in Vibrio). Furthermore, exposure to 300 µg/L significantly decreased levels of bile acids and glycerophospholipids while triggering intestinal inflammation but activating self-protective mechanisms such as antibiotic presence. Notably, even exposure to 30 µg/L of Sb can trigger dysbiosis of intestinal microbiota and metabolites, potentially impacting fish health through the "microbiota-intestine-brain axis" and contributing to disease initiation. This study provides valuable insights into toxicity-related information concerning environmental impacts of Sb on aquatic organisms with significant implications for developing management strategies. [Display omitted] • Sb caused histopathological damage to the intestine of adult zebrafish. • Sb triggered oxidative stress and inflammatory responses in the intestine. • Sb disrupted intestinal microbial community and metabolism profiles. • Sb can modulate the "microbiota-intestine-brain axis" via intestinal microbiota. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals known for their widespread use and persistence in the environment. Laboratory and epidemiological studies investigating these compounds have signaled their neurotoxic and endocrine-disrupting propensities, prompting further research into their effects on behavioral stress responses and their potential role as risk factors for stress-related disorders such as anxiety and depression. This study elucidates the ramifications of early developmental exposures to individual and combined PFAS on the development and behavioral stress responses of larval zebrafish (Danio rerio), an established model in toxicological research. Wild-type zebrafish embryos were enzymatically dechorionated and exposed to PFOS, PFOA, PFHxS, and PFHxA between 6 and 120 h post-fertilization (hpf). We targeted environmentally relevant concentrations stemming from the USEPA 2016 Hazard Advisory Limit (HAL, 0.07 μg/L) and folds higher (0.35, 0.7, 1.75, and 3.5 μg/L). Evaluations at 120 hpf encompassed mortality, overall development, developmental defects, and larval activity both at baseline stress levels and following exposure to acute stressors (acoustic and visual). Larval exposure to PFOA, PFOS, or PFHxS (0.07 μg/L or higher) elicited significant increases in mortality rates, which capped at 23.1%. Exposure to individual chemicals resulted in limited effects on overall development but increased the prevalence of developmental defects in the body axis, swim bladder, pigmentation, and eyes, as well as the prevalence of yolk sac and pericardial edemas. Larval activity at baseline stress levels and following exposure to acute stimuli was significantly altered. Combined exposure to all four chemicals intensified the breadth of developmental and behavioral alterations, suggesting possible additive or synergistic effects. Our findings shed light on the developmental and neurobehavioral disturbances associated with developmental exposure to PFAS at environmentally relevant concentrations, the added risks of combined exposures to these chemicals, and their possible role as environmental risk factors for stress-related disorders. [Display omitted] • Exposure to PFAS at concentrations deemed environmentally relevant. • PFAS developmental exposures alter survival and development. • PFAS exposures alter behavioral stress responses. • Combined exposures to PFAS produce added toxicological effects. [ABSTRACT FROM AUTHOR]

PFDMO2OA (C8 HFPO-TA), a novel substitute for perfluorooctanoic acid (PFOA), has been frequently detected in surface waters. However, information on its toxicity remains scarce. In the present study, zebrafish embryos were exposed to varying concentrations of PFDMO2OA, ranging from 80 to 800 mg/L, until 120 h post-fertilization (hpf) to explore its potential developmental toxicities. The LC50 value for mortality was 505.9 mg/L, comparable to that of PFOA (over 500 mg/L), suggesting a lack of safety of PFDMO2OA compared to PFOA. At 120 hpf, PFDMO2OA exposure led to various malformations in embryos, including uninflated swim bladder, yolk sac oedema, spinal deformation, and pigmentation changes, with pericardial oedema being prominent. Analysis using O-dianisidine stain indicated a decline in erythrocytes over time. Transcriptome analysis further revealed the cardiovascular toxicity caused by PFDMO2OA at the molecular level. Time-course differential analysis pointed to the apoptosis dependent on disrupted mitochondrial function as a significant contributor to erythrocyte disappearance, as confirmed by the TUNEL stain. Therefore, the present findings suggest that PFDMO2OA induces developmental malformations and cardiovascular toxicities in zebrafish embryos, demonstrating a toxic potency comparable to that of PFOA. The results further highlight the significance of evaluating the health risks associated with PFDMO2OA. [Display omitted] • Exposure to PFDMO2OA resulted in various malformations in zebrafish embryos. • Cardiovascular toxicity emerged as the most prominent phenotype. • Time-course transcriptome analysis elucidated the pathogenic mechanism. • Apoptosis participates in the process of PFDMO2OA-induced erythrocyte disappearance. [ABSTRACT FROM AUTHOR]

A risk assessment on the aquatic toxicity of the plant biostimulant strigolactone mimic (2-(4-methyl-5-oxo-2,5-dihydro-furan-2-yloxy)-benzo[de]isoquinoline-1,3-dione (SL-6) was performed using a suite of standardised bioassays representing different trophic groups and acute and chronic endpoints. In freshwater, three trophic groups of algae, crustacea and fish were used. Whilst in seawater, algae (unicellular and macroalgae), Crustacea and Mollusca were employed. In addition, the genotoxicity of SL-6 was determined with the comet assessment performed on unicellular marine algae, oysters, and fish embryos. This was the first time ecotoxicity tests have been performed on SL-6. In freshwater, the lowest LOEC was measured in the unicellular algae at 0.31 mg/L SL-6. Although, similar LOEC values were found for embryo malformations and impacts on hatching rate in zebrafish (LOEC 0.31–0.33 mg/L). Consistent malformations of pericardial and yolk sac oedemas were identified in the zebrafish embryos at 0.31 mg/L. In marine species, the lowest LOEC was found for both Tisbe battagliai mortality and microalgae growth at an SL-6 concentration of 1.0 mg/L. Significant genotoxicity was observed above control levels at 0.0031 mg/L SL-6 in the unicellular algae and 0.001 mg/L SL-6 in the oyster and zebrafish larvae. When applying the simple risk assessment, based on the lowest NOECs and appropriate assessment factors, the calculated predicted no effect concentration (PNEC), for the ecotoxicity and the genotoxicity tests were 1.0 µg/L and 0.01 µg/L respectively. [Display omitted] • This was the first toxicity assessment of the strigolactone mimic SL-6 to aquatic organisms. • SL-6 concentrations of 0.31 mg/L caused pericardial and yolk-sac oedemas in zebrafish larvae. • Genotoxicity was observed at 0.001 mg/L SL-6 in the oyster and zebrafish larvae. • PNECs of 1.0 µg/L and 0.01 µg/L SL-6 were calculated for ecotoxic and genotoxic effects. [ABSTRACT FROM AUTHOR]

The transmission of various infectious diseases, by Aedes aegypti and Anopheles stephensi has poses a menace to human well-being. To combat the vector of this serious disease, environmentally friendly prevention strategies are essential. The fight against malaria and dengue is greatly aided by nanotechnology and pharmacology. The aqueous leaf extract of Zaleya decandra was used in the present study to synthesise palladium nanoparticles (Zd -PdNPs) by simple and sustainable processes. Numerous physiochemical methods were used to identify and classify bio-synthesized Zd -PdNPs. Additionally, Ae. aegypti and An. stephensi IV instar larvae were tested toxicity using Z. decandra extract and Zd -PdNPs. Further research was conducted to determine how the NPs-based treatment affected the histology and morphology of mosquito larvae. The LC 50 values of ZD-PdNPs against Ae. aegypti larvae were 18.071 and 14.124 µg/mL; An. stephensi had 12.140 and 10.118 µg/mL at 12 and 24 hr exposure. Furthermore, zebrafish embryo developmental toxicity and the freshwater sludge worm Tubifex tubifex have both been utilised as test models for non-target eco-toxicological investigations in the typical laboratory setting. Gas chromatography-mass spectrometry was used to examine the chemical constituents of Z. decandra. n-hexadecanoic acid, 6-octadecenoic acid, phthalic acid, butyl undecyl ester, squalene, nonanoic acid, methyl ester, and butyl undecyl ester 2-methyl-4-phenylthiolane were identified as potential compounds for bio reduction and synthesis of nanoparticle. The current study reveals that natural molecules bonded nanomaterial that are effective against human disease spreading mosquito vectors larvae and highlights the potential value of Nano-larvicides as well as environmental safety. [Display omitted] • Green Palladium NPs: Zd -PdNP synthesis with Zaleya decandra. • Toxic to Mosquito Larvae: Zd -PdNPs combat Aedes & Anopheles. • Eco-Safe Assessment: Zebrafish embryos & Tubifex tubifex. • Bioactive Compounds: GC helps find nanoparticle-making compounds. [ABSTRACT FROM AUTHOR]

N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPDQ) has raised significant concerns due to its widespread distribution and high toxicity to aquatic organisms. However, the cardiac developmental toxicity of 6PPDQ and the underlying mechanisms remain unclear. In this study, we observed no notable alterations in heart morphology or embryo survival in zebrafish embryos exposed to 6PPDQ (0.2–2000 μg/L) up to 3 days post-fertilization (dpf). However, concentrations at 2 μg/L or higher induced cardiac dysfunctions, leading to lethal effects at later stages (6–8 dpf). We further found that the aryl hydrocarbon receptor (AHR) inhibitor CH22351 attenuated 6PPDQ-induced cardiac dysfunctions, implicating the involvement of AHR signal pathway. Moreover, 6PPDQ exposure led to an overproduction of reactive oxygen species (ROS) and an upregulation of genes associated with oxidative stress (sod1 , sod2 , and nrf2a). This was accompanied by an increase in oxidative DNA damage and the induction of p53-dependent extrinsic apoptosis. Co-exposure to the ROS scavenger N-acetylcysteine effectively counteracted the DNA damage and apoptosis induced by 6PPDQ. Importantly, inhibition of AHR or its downstream target cyp1b1 attenuated 6PPDQ-induced oxidative stress, DNA damage, and apoptosis. In conclusion, our results provide evidence that 6PPDQ induces oxidative stress through the AHR/cyp1b1 signaling pathway, leading to DNA damage and extrinsic apoptosis, ultimately resulting in cardiac dysfunction. [Display omitted] • 6PPDQ at an environmental relevant concentration induces cardiac dysfunction in zebrafish embryos. • Aryl hydrocarbon receptor signaling mediates 6PPDQ-induced cardiac dysfunction. • Aryl hydrocarbon receptor activated by 6PPDQ induces oxidative stress and DNA damage. • 6PPDQ triggers p53-dependent exogenous apoptosis in zebrafish embryonic hearts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The development of new biomaterials and drug delivery systems necessitates animal experimentation to demonstrate biocompatibility and therapeutic efficacy. Reduction and replacement of the requirement to conduct experiment using full-grown animals has been achieved through utilising zebrafish embryos, a promising bridge model between in vitro and in vivo research. In this review, we consider how zebrafish embryos have been utilised to test both the biocompatibility of materials developed to interact with the human body and drug release studies. Furthermore, we outline the advantages and limitations of this model and review legal and ethical issues. We anticipate increasing application of the zebrafish model for biomaterial evaluation in the near future. This review aims to evaluate the potential application and suitability of the zebrafish model in the development of biomaterials and drug delivery systems. It creates scientific impact and interest because replacement models are desirable to the society and the scientific community. The continuous development of biomaterials calls for the need to provide solutions for biological testing. This review covers the topic of how the FET model can be applied to evaluate biocompatibility. Further, it explores the zebrafish from the wild-type to the mutant form, followed by a discussion about the ethical considerations and concerns when using the FET model. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Spirotetramat (SPT), a tetronic acid-derived insecticide, is implicated in reproductive and lipid metabolism disorders, as well as developmental toxicity in fish. While these effects are documented, the precise mechanisms underlying its developmental toxicity are not fully elucidated. In this study, zebrafish embryos (2 h post-fertilization, hpf) were exposed to four concentrations of SPT (0, 60, 120, and 240 μg/L) until 21 dpf (days post-fertilization). We delved into the mechanisms by examining its potential disruption of the thyroid endocrine system, employing in vivo , in vitro , and in silico assays. The findings showed notable developmental disturbances, including reduced hatching rates, shortened body lengths, and decelerated heart rates. Additionally, there was an increase in malformations and a decline in locomotor activity. Detailed analyses revealed that SPT exposure led to elevated thyroid hormone levels, perturbed the hypothalamic-pituitary-thyroid (HPT) axis transcript levels, amplified deiodinase type I (Dio1) and deiodinase type II (Dio2) activities, and both transcriptionally and proteomically upregulated thyroid receptor beta (TRβ) in larvae. Techniques like molecular docking and surface plasmon resonance (SPR) confirmed SPT's affinity for TRβ, consistent with in vitro findings suggesting its antagonistic effect on the T3-TR complex. These insights emphasize the need for caution in using tetronic acid-derived insecticides. [Display omitted] • Spirotetramat induced hyperthyroidism and altered thyroid gland morphology in larval zebrafish. • HPT axis-related genes were significantly modulated after spirotetramat exposure. • Molecular docking revealed high affinity of spirotetramat for fish thyroid receptor beta (TRβ). • Spirotetramat acted as an agonist for TRβ and an antagonist for the T3-TR complex. • SPR assay showed moderate binding ability of spirotetramat to the thyroid receptor. [ABSTRACT FROM AUTHOR]

The unprecedented proliferation of disposable face masks during the COVID-19 pandemic, coupled with their improper disposal, threatens to exacerbate the already concerning issue of plastic pollution. This study evaluates the role of environmentally weathered masks as potential sources of microplastics (MPs) and nanoplastics (NPs) and assesses their adverse impact on the early life stages of zebrafish. Experimental findings revealed that a single disposable mask could release approximately 1.79 × 109 particles, with nearly 70% measuring less than 1 μm, following 60 days of sunlight exposure and subsequent sand-induced physical abrasion. Remarkably, the MPs/NPs (MNPs) emanating from face masks have the potential to permeate the outer layer (chorion) of zebrafish embryos. Furthermore, due to their minute size, these particles can be consumed by the larvae's digestive system and subsequently circulated to other tissues, including the brain. Exposure to mask-derived MNPs at concentrations of 1 and 10 μg/L led to significant cases of developmental toxicity, incited oxidative stress, and prompted cell apoptosis. A subsequent metabolomics analysis indicated that the accumulation of these plastic particles perturbed metabolic functions in zebrafish larvae, primarily disrupting amino acid and lipid metabolism. The outcomes of this research underscore the accelerating possibility of environmental aging processes and physical abrasion in the release of MNPs from disposable face masks. Most importantly, these results shed light on the possible ecotoxicological risk posed by improperly disposed of face masks. [Display omitted] • Natural weathering process induced great release of MP/NP from face mask. • Mask-derived MP/NP could accumulate into zebrafish embryos and larvae. • Accumulated MP/NP resulted in significant developmental toxicity in zebrafish larvae. • Mask-derived MP/NP induced oxidative stress and apoptosis in larval zebrafish. • Mask-derived MP/NP caused metabolism disorder in larval zebrafish. [ABSTRACT FROM AUTHOR]

Fungal compounds are believed to be the most efficient method of addressing challenges with pesticide resistance and contamination of the environment. The present study was aimed to evaluate the larvicidal, pupicidal, ovicidal, histopathology profile, antibacterial, cytotoxic effects of cervical cancerous cells and its toxicity assessments using zebrafish embryo (Danio rerio). The isolates were confirmed by macroscopic, microscopic and PCR using a universal internal transcribed spacer primer for the molecular identification of the isolated fungus at the species level (GenBank - MN049541). The isolated fungus was first tested for its ability to produce toxic compounds in Aedes aegpti larvae in the 1–4th instar. For each instar of determined mosquito larvae, the secondary metabolites were evaluated in different bioassays at different test concentrations (100–500 μg/mL). The lethal concentrations of A. macrospora mycelial ethyl acetate extract that kill 50% of exposed larvae (LC 50) and 90% of exposed larvae (LC 90) were found in the first, second, third, and fourth instar larvae of A. aegypti (LC 50 = 96.167, 131.370, 217.595, and 143.864 μg/mL and (LC 90 = 395.16, 483.692, 882.545, and 655.722 μg/mL). After 120 h of exposure, the ovicidal bioassay's mean (%) was observed. A dose-dependent pattern was found in the enzymatic level of acetylcholinesterase in 4th instar larvae exposed to fungal mycelial metabolites. The treatment of 500 μg/mL of mycelia metabolites produced significant histopathological damage in the 4th instar mosquito larvae. The highest growth inhibition zones were observed during the antibacterial investigation of Alternaria macrospora metabolites against E. coli (22 mm) and S. aureus (20 mm). Also, the detected mycelium metabolites were tested for docking studies to identify their binding ability towards the E. coli FimH and S. aureus tyrosyl-RNA synthetase protein. The mycelium metabolites with different concentrations were further tested in the in-vivo zebrafish model to evaluate developmental toxicity. This is the first report on mosquito larvicidal and pupicidal activity of ethyl acetate metabolites produced by A. macrospora species. The study findings demonstrate that A. macrospora metabolites might be an ideal, cheap, small, and environmentally suitable source for controlling A. aegypti larvae. • The highest mortality rate (100%) was seen in A. aegypti first to fourth instar larvae at 500 μg/mL concentration. • The result achieved was an average ovicidal effect of 100%. • AChE activity was decreased in the selected larvae exposed to A. macrospora metabolites. • Antibacterial properties of A. macrospora metabolite exhibited maximum growth inhibition zone observed in E. coli (22 mm). • A. macrospora metabolites 1 mg/mL were found to be non-toxic to Zebrafish embryos. [ABSTRACT FROM AUTHOR]

Natural aquatic environments have a heterogeneous composition; therefore, simultaneous exposure to multiple contaminants is relevant and more realistic when assessing exposure and toxicity. This study examines the combinatorial effects of two compounds found ubiquitously in drinking water across the United States: glyphosate and lead acetate. Zebrafish (Danio rerio) embryos were used as a model for investigating developmental delays following controlled exposures. Six different environmentally relevant exposure concentrations of glyphosate, ranging from 0.001 to 10 ppm, and lead acetate, ranging from 0.5 to 4 ppm, were applied first as single exposures and then as co-exposures. The sublethal endpoints of hatching and coagulation were quantified to determine potencies. Results indicate that higher concentrations of the individual chemicals correlate with later hatching with correlation coefficients of 0.71 and 0.40 for glyphosate and lead acetate respectively, while the co-exposure at lower concentrations induced earlier hatching with a correlation coefficient 0.74. In addition, increased levels of coagulation and glutathione reductase activity were observed following co-exposure, as compared to the individual exposures, suggesting potential toxicological interactions. These results support the need for further work assessing the combined potencies of aquatic contaminants rather than individual exposures. • Exposure to multiple contaminants is realistic when assessing exposure and toxicity. • Higher concentrations of the individual chemicals correlate with later hatching. • Co-exposure at lower concentrations induced earlier hatching. • Increased coagulation and glutathione reductase were observed in co-exposure, suggesting interactions. • Chemical use should be reevaluated in the context of chemical interactions. [ABSTRACT FROM AUTHOR]

Glyphosate, a globally prevalent herbicide known for its selective inhibition of the shikimate pathway in plants, is now implicated in physiological effects on humans and animals, probably due to its impacts in their gut microbiomes which possess the shikimate pathway. In this study, we investigate the effects of environmentally relevant concentrations of glyphosate on the gut microbiota, neurotransmitter levels, and anxiety in zebrafish. Our findings demonstrate that glyphosate exposure leads to dysbiosis in the zebrafish gut, alterations in central and peripheral serotonin levels, increased dopamine levels in the brain, and notable changes in anxiety and social behavior. While the dysbiosis can be attributed to glyphosate's antimicrobial properties, the observed effects on neurotransmitter levels leading to the reported induction of oxidative stress in the brain indicate a novel and significant mode of action for glyphosate, namely the impairment of the microbiome-gut-axis. While further investigations are necessary to determine the relevance of this mechanism in humans, our findings shed light on the potential explanation for the contradictory reports on the safety of glyphosate for consumers. • Glyphosate affects zebrafish brain and behaviour. • Selective antibiotic properties of glyphosate may result in dysbiosis. • Alterations in serotonin and dopamine levels may be related to dysbiosis. • A potential novel mechanism for glyphosate toxicity in vertebrates. [ABSTRACT FROM AUTHOR]

Acid mine drainage (AMD) is widely acknowledged as a substantial threat to the biodiversity of aquatic ecosystems. The present study aimed to study the toxicological effects of Cu-rich AMD from the Sulitjelma mine in zebrafish larvae. The AMD from this mine was found to contain elevated levels of dissolved metals including Mg (46.7 mg/L), Al (20.2 mg/L), Cu (18.3 mg/L), Fe (19.8 mg/L) and Zn (10.6 mg/L). To investigate the toxicological effects, the study commenced by exposing zebrafish embryos to various concentrations of AMD (ranging from 0.75% to 9%) to determine the median lethal concentration (LC 50). Results showed that 96 h LC 50 for zebrafish larvae following AMD exposure was 2.86% (95% CI: 2.32–3.52%). Based on acute toxicity results, zebrafish embryos (<2 hpf) were exposed to 0.1% AMD (Cu: 21.7 µg/L) and 0.45% AMD (Cu: 85.7 µg/L) for 96 h to assess development, swimming behaviour, heart rate, respiration and transcriptional responses at 116 hpf. Light microscopy results showed that both 0.1% and 0.45% AMD reduced the body length, eye size and swim bladder area of zebrafish larvae and caused phenotypic abnormalities. Swimming behaviour results showed that 0.45% AMD significantly decreased the locomotion of zebrafish larvae. Heart rate was not affected by AMD exposure. Furthermore, exposure caused a significant increase in oxygen consumption indicating vascular stress in developing larvae. Taken altogether, the study shows that even heavily diluted AMD with environmentally relevant levels of Cu caused toxicity in zebrafish larvae. [Display omitted] • Acid mine drainage (AMD) is a threat to aquatic organisms. • Copper-rich runoff from mines causes phenotypic deformities in fish larvae. • Swimming behavior and respiration impaired by diluted AMD. • Thousand-fold diluted ADM causes toxicity in zebrafish larvae. [ABSTRACT FROM AUTHOR]

Studies on the comparison of developmental (neuro) toxicity of parabens are currently limited, and unharmonized concentrations between phenotypic observations and transcriptome analysis hamper the understanding of their differential molecular mechanisms. Thus, developmental toxicity testing was conducted herein using the commonly used methyl- (MtP), ethyl- (EtP), and propyl-parabens (PrP) in zebrafish embryos. With a benchmark dose of 5%, embryonic-mortality-based point-of-departure (M-POD) values of the three parabens were determined, and changes in locomotor behavior were evaluated at concentrations of 0, M-POD/50, M-POD/10, and M-POD, where transcriptome analysis was conducted to explore the underlying neurotoxicity mechanism. Higher long-chained parabens were more toxic than short-chained parabens, as determined by the M-POD values of 154.1, 72.6, and 24.2 µM for MtP, EtP, and PrP, respectively. Meanwhile, exposure to EtP resulted in hyperactivity, whereas no behavioral effect was observed with MtP and PrP. Transcriptome analysis revealed that abnormal behaviors in the EtP-exposed group were associated with distinctly enriched pathways in signaling, transport, calcium ion binding, and metal binding. In contrast, exposure to MtP and PrP mainly disrupted membranes and transmembranes, which are closely linked to abnormal embryonic development rather than neurobehavioral changes. According to the changes in the expressions of signature mRNAs, tentative transcriptome-based POD values for each paraben were determined as MtP (2.68 µM), EtP (3.85 µM), and PrP (1.4 µM). This suggests that different molecular perturbations initiated at similar concentrations determined the extent and toxicity outcome differently. Our findings provide insight into better understanding the differential developmental neurotoxicity mechanisms of parabens. [Display omitted] • Longer-chained propylparaben had greater acutely embryonic toxicity than methyl- and ethyl-parabens. • Hyperactivity was induced only by ethyl-paraben. • Hyperactivity was associated with disrupted pathways in signaling, transport, calcium ion binding, and metal binding. • RNA-seq analysis revealed that the three parabens had different molecular mechanisms. • Transcriptome-based-POD values were similar among the three parabens [ABSTRACT FROM AUTHOR]

Due to Butylparaben (BuP) widespread application in cosmetics, food, pharmaceuticals, and its presence as an environmental residue, human and animal exposure to BuP is common, potentially posing hazards to both human and animal health. Congenital heart disease is already a serious problem. However, the effects of BuP on the developing heart and its underlying mechanisms remain unclear. Here, zebrafish embryos were exposed to environmentally and human-relevant concentrations of BuP (0.6 mg/L, 1.2 mg/L, and 1.8 mg/L, calculated but not measured) at 6 h post-fertilization (hpf) and were treated until 72 hpf. Exposure to BuP led to cardiac morphological defects and cardiac dysfunction in zebrafish embryos, manifesting symptoms similar to systolic heart failure. The etiology of BuP-induced systolic heart failure in zebrafish embryos is multifactorial, including cardiomyocyte apoptosis, endocardial and atrioventricular valve damage, insufficient myocardial energy, impaired Ca2+ homeostasis, depletion of cardiac-resident macrophages, cardiac immune non-responsiveness, and cardiac oxidative stress. However, excessive accumulation of reactive oxygen species (ROS) in the cardiac region and cardiac immunosuppression (depletion of cardiac-resident macrophages and cardiac immune non-responsiveness) may be the predominant factors. In conclusion, this study indicates that BuP is a potential hazardous substance that can cause adverse effects on the developing heart and provides evidence and insights into the pathological mechanisms by which BuP leads to cardiac dysfunction. It may help to prevent the BuP-based congenital heart disease heart failure in human through ameliorating strategies and BuP discharge policies, while raising awareness to prevent the misuse of preservatives. [Display omitted] • BuP can cause zebrafish embryonic systolic heart failure. • BuP damages cardiac-resident macrophages in zebrafish embryos. • BuP impairs the cardiac immune response in zebrafish embryos. • Endocardial defects induced by BuP are related to the downregulation of klf2a. • The ROS caused by BuP mainly accumulate in the zebrafish embryo heart region. [ABSTRACT FROM AUTHOR]

Determination of cellular signaling in live embryos is key to understand the molecular processes that drive development. Here, we show that a transgenic mouse line carrying a luciferasebased gene reporter of Gli-mediated transcriptional activation (Gli-Luc) displays sonic hedgehog (Shh) signaling in discrete developmental processes during short-term cultures of whole embryos or embryo explants. The bioluminescence in E9.5 embryos was detected in regions in which Shh activity has been demonstrated. Later, in E10.5 embryos, bioluminescence intensity markedly increased, mostly corresponding to the high Shh activity of the developing midbrain and limb. Notably, the dynamic range of the Gli-Luc reporter in the developing limb revealed the progressive emergence of bioluminescence in the zone of polarizing activity, where reporter activity locally increased and spatially spread in agreement with the signaling gradient expected for Shh. In the midbrain of E9.5 mouse embryos, bioluminescence was not detected along the ventral region as expected but, instead, Shh-dependent anterior and posterior bioluminescence foci emerged by E10.5 indicating that the Gli-Luc reporter can only respond transcriptionally to relatively high levels of GliA and/or without the interaction with other transcription factors. The present work supports the use of bioluminescence to identify and study the dynamics of centers of morphogen signaling during mouse embryogenesis. [ABSTRACT FROM AUTHOR]

Zebrafish lateral line neuromasts are composed of central hair cells surrounded by supporting cells. Cisplatin is a common anticancer drug, with hair cell disruption being a frequent side effect of this drug. In our study, we observed complete functional hair cell loss after six hours of cisplatin insult in neuromasts, as demonstrated by anti-parvalbumin 3 immunofluorescence staining or YO-PRO1 vital dye staining. Time course analysis of neuromast hair cell regeneration showed that regenerated hair cells first appeared between 12 and 24 h after damage, and the abundance of these cells increased stepwise with recovery time. After 72 h, 90% of the hair cells were regenerated, and after 84 h, the number of regenerated hair cells was comparable to the number of neuromast hair cells before treatment. The expression pattern of slc17a8 also showed that hair cells were regenerated after cisplatin exposure. Meanwhile, peripheral supporting cells moved toward the center of the neuromasts, as shown by the in situ expression pattern of sox21a. Increased hair cell progenitor formation was also observed, as demonstrated by the in situ expression pattern of atoh1a. Furthermore, we detected increased expression of wnt2 , wnt3a , and ctnnb1 in sorted supporting cells from the sqet10 transgenic line, which labels neuromast supporting cells specifically. In situ hybridization analysis also showed decreased expression of dkk1a and dkk2. Regenerated hair cells were inhibited by early inhibition of Wnt/β-catenin signaling. Taken together, the results presented here showed that Wnt/β-catenin signaling was activated in supporting cells during cisplatin exposure earlier than expected. Our results also indicated that supporting cells enabled hair cell regeneration via Wnt/β-catenin signaling during cisplatin exposure. [ABSTRACT FROM AUTHOR]

Gabapentin (GPT) has become an emerging contaminant in aquatic environments due to its wide application in medical treatment all over the world. In this study, embryos of zebrafish were exposed to gabapentin at realistically environmental concentrations, 0.1 μg/L and 10 μg/L, so as to evaluate the ecotoxicity of this emergent contaminant. The transcriptomics profiling of deep sequencing was employed to illustrate the mechanisms. The zebrafish (Danio rerio) embryo were exposed to GPT from 12 hpf to 96 hpf resulting in 136 and 750 genes differentially expressed, respectively. The results of gene ontology (GO) analysis and the Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis illustrated that a large amount of differentially expressed genes (DEGs) were involved in the antioxidant system, the immune system and the nervous system. RT-qPCR was applied to validate the results of RNA-seq, which provided direct evidence that the selected genes involved in those systems mentioned above were all down-regulated. Acetylcholinesterase (AChE), lysozyme (LZM) and the content of C-reactive protein (CRP) were decreased at the end of exposure, which is consistent with the transcriptomics results. The overall results of this study demonstrate that GPT simultaneously affects various vital functionalities of zebrafish at early developmental stage, even at environmentally relevant concentrations. Image 1 • The ecotoxicity of gabapentin to zebrafish embryos was measured. • Transcriptomic techniques were applied to illustrate the underlying mechanisms. • The antioxidant, immune and nervous system of zebrafish were significantly affected. The present study illustrates the toxic effects of gabapentin to zebrafish at early developmental stage at environmentally relevant concentrations, and the mechanisms behind. [ABSTRACT FROM AUTHOR]

Microplastics have been frequently detected in both marine and freshwater ecosystems. Their impact on aquatic organisms has raised much concern. This study investigated the impact of microplastics on zebrafish embryos and larvae, with a special focus on their swimming competence. The zebrafish embryos were exposed to microplastics starting from 4 h post fertilization. Microplastics first adhered to the embryo chorion, then entered the stomach and intestinal tract of the larvae later. In the free swimming test, exposure to 1000 μg/L (around 1.91 × 107 particles/L) of microplastics led to a significant decrease in both swimming distance and speed of zebrafish larvae under the dark condition by 3.2% and 3.5% respectively. In the alternating light-to-dark photoperiod stimulation assay, exposure to 100 and 1000 μg/L (around 1.91 × 106 and 1.91 × 107 particles/L) of microplastics caused a 4.6% and 2.6% decrease in swimming distance, and reduced the active speed by 4.9% and 2.8%, possibly as a result of inhibited dark avoidance in treated zebrafish larvae. At the molecular level, exposure to microplastics induced upregulated expression of inflammation (il1b) and oxidative stress (cat) related genes. This study demonstrates that exposure to microplastics significantly decreases larvae swimming competence, which may have significant impacts on its population fitness in the aquatic environment and further ecological consequences. Image 1 • Zebrafish larvae took up a significant amount of microplastics, with a large amount entering the digestive system. • Microplastics significantly decreased swimming competence of the zebrafish larvae in the free swimming test. • Microplastics significantly decreased larvae swimming competence in the alternating light-to-dark stimulation assay. • Inflammation (il1b) and oxidative stress (cat) related genes were significantly upregulated upon exposure to microplastics. [ABSTRACT FROM AUTHOR]

Abstract Polychlorinated biphenyls (PCBs), a class of persistent organic pollutant, are closely related to abnormal eye development in children. However, little is known regarding the role of peptides in the development of PCB-induced ocular dysplasia. To characterize the nature of PCB exposure on peptides involved in the development of the ocular system, we used liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) to detect differential expression of peptides between normal and PCB-exposed zebrafish embryos. A total of 7900 peptides were analyzed, 90 of which were differentially expressed, with 29 being up-regulated and 61 down-regulated. These peptides were investigated using ingenuity pathway analysis (IPA) and gene ontology (GO) analysis to explore their role in eye development. This study identified 18 peptides associated with the development of the optic nerve and ocular system in the PCB-exposure group, as well as 10 peptides that are located in the functional domain of their precursor proteins. These peptides provide potential biomarkers for the treatment of ocular dysplasia caused by PCBs and may help us understand the mechanism of abnormal eye development caused by organic pollutants. Highlights • Polychlorinated biphenyls (PCBs) are an environmental organic pollutant closely related to abnormal retinal development. • Liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) were used. • These peptides provide potential biomarkers for the treatment of ocular dysplasia. [ABSTRACT FROM AUTHOR]

β-Blockers (BB) are one of the most commonly prescribed pharmaceuticals used for treating cardiovascular and acute anxiety-related disorders. This class of drugs inhibit β-adrenoceptor signalling and given their growing, widespread use, BB are routinely detected in surface waters at nM concentrations. This is concerning as trace levels of BB impart developmental and reproductive dysfunction in non-target aquatic organisms, with potential for ecological risks. To date, environmental pharmaceutical risks to non-target animals are not part of the monitoring framework due to the lack of bioassays for assessing their biological effects. Behavioral endpoints have the advantage of a systems-level integration of multiple sensory signals and motor responses for toxicity screening; however, they are not currently used for risk assessment of environmental contaminants. The zebrafish (Danio rerio) embryo photomotor response (zfPMR) has been used in high-throughput behavioral screenings for neuroactive drug effects at high, therapeutic concentrations. Our objective here was to examine if we could utilize the zfPMR for screening environmental levels of BB. Embryos were placed into 96-well plates, exposed to chemicals and/or municipal wastewater effluent (MWWE), and their zfPMRs were measured with video-analysis. To specifically target BB, embryos were co-treated with isoproterenol, a β-adrenergic agonist that stimulates the zfPMR, and the inhibition of isoproterenol-induced response was used as a biomarker of BB exposure. Our results reveal that the inhibition of isoproterenol-stimulated zfPMRs can be used as a biosensor capable of detecting BB in the parts-per-billion to parts-per-trillion in water samples, including diluted MWWE. The method developed detects BB in spite of the presence of other neuroactive compounds in water samples. This systems level approach of rapid screening for BB effects provides the most promising evidence to date that behavioral neuromodulation can be potentially applied for environmental effects monitoring of pharmaceuticals. Image 1 • zfPMR is a rapid drug screening assay with potential for environmental application. • Isoproterenol stimulates zfPMR, and β-blockers (BB) inhibit this response. • Environmental levels of propranolol inhibit the isoproterenol-stimulated zfPMR. • Municipal wastewater effluent inhibits the isoproterenol-stimulated zfPMR. • Isoproterenol-stimulated zfPMR can be used as a biosensor for environmental BB. [ABSTRACT FROM AUTHOR]

Abstract The final fate of many drugs is release into the natural aquatic environment. It is necessary to assess the toxicity caused by this situation and the associated concerns for human beings. Zebrafish (Danio rerio) is a common biomodel used to assess toxicity in aquatic environments. The zebrafish embryo toxicity test was selected to evaluate the acute toxicity of several drugs (diphenhydramine, gentamicin, tobramycin, enalapril and lidocaine) due to the lack of such information. Lethal and sublethal effects were detected, and the LC 50 values of the drugs ranged from 11.0 mg/L to 422·102 mg/L. For all of the drugs tested, these values were higher than the concentrations found in the natural environment. Therefore, there was a low environmental toxicological risk. Nevertheless, teratogenic effects were also recorded when embryos of zebrafish were exposed to caffeine (control drug), diphenhydramine and lidocaine at lower concentrations than the respective LC 50 values. Quantitative structure–activity relationship analysis was also performed to analyse these drugs and other chemicals with pharmaceutical uses as well as previous toxicological data in this vertebrate after 48 h of exposure. It is estimated that the partition coefficient, log P, is the main physicochemical property related to the ecotoxicological data and can be used for the development of a mathematical model. Highlights • The FET was selected to evaluate the acute toxicity of several drugs. • Results indicate a low environmental risk (LC 50 > environmental concentration). • The QSAR revealed that Log P is the property that best fits the data. • QSAR analysis improves the correlation when lethal activity is using for classifying. • For Cramer classification, class I chemical group showed the best correlation. [ABSTRACT FROM AUTHOR]

Abstract Ionizable strategies are routinely used to enhance the solubility and dissolution rates of various pharmaceuticals. These chemicals may directly affect aquatic environment once discharged from factories, hospitals or livestock farms. Here, we assessed the potential side effect of tetracyclines (TCs) on the development of zebrafish embryos. Tetracycline hydrochloride decreased water pH from 6.4 to 4.4 at 30 mg/L. Acidified water exceeded the tolerance of zebrafish embryos in pure water during the early ten hours post fertilization (hpf). Interestingly, we found that Ca2+ in the embryo medium could increase the tolerance of embryos to acidified water. Furthermore, we found that the protection of Ca2+ was not due to the formation of TCs-Ca2+ complexes under acidic condition, based on spectral analysis. Meanwhile we showed that exogenous addition of Ca2+ could inhibit the accumulation of Ca2+ from the cytoplasm to the surface of embryos. These results may shed light on the strategies for protecting aquatic animals from acidic environments. Highlights • Evaluation system could affect the toxicity of TCs. • Ca2+ boosted the tolerance of embryos against water acidification. • Exogenous Ca2+ inhibited the accumulation of Ca2+ on the surface of embryos. [ABSTRACT FROM AUTHOR]

Abstract Diuron is an herbicide, which is used to control a wide variety of annual and perennial broadleaf, grassy weeds, and mosses. However, the toxicity of diuron in HepG2 cells and zebrafish embryos was unclear. In this study, HpeG2 cells and zebrafish embryos were exposed to different concentrations of diuron for 24 h and 48 h, respectively. Results reveal the diuron caused cytotoxicity and the generation of reactive oxygen species (ROS) in the treated HepG2 cells. The effects of diuron on the expression of catalase and superoxide dismutase (SOD1 and SOD2), an antioxidant enzyme, were investigated. Results showed that only SOD1 was significantly induced after treated diuron 48 h, but the expression of catalase and SOD2 was unaffected. Additionally, the cytotoxicity of diuron was not attenuated in cells pretreated with of N-acetyl-cysteine (NAC), a well-known antioxidant, indicating that oxidative stress could not contribute to cellular death in the treated HepG2 cells. In zebrafish embryos, results from proteomic analysis show that 332 differentially upregulated proteins and 199 down-regulated proteins were detected in the treated embryos (P < 0.05). In addition to the up-regulated antioxidant proteins (prdx3, cat, prdx4, txnrd1, prdx1, sod1, prdx2, and sod2), some decreased proteins were related to cytoskeleton formation, tight junction, and gap junction, which could be related to the malformation of the treated zebrafish embryos. In summary, diuron caused cytotoxicity in HepG2 cells, and the mechanisms of toxicity in zebrafish were addressed using the proteomic analysis. Highlights • Diuron caused cytotoxicity in HepG2 cells. • Diuron cause protein dysregulation in zebrafish embryos. • Diuron upregulated some proteins related to metabolic pathways and oxidative stress. • Diuron downregulated some proteins related to the pathways of ribosome, tight junction and gap junction. • Proteomic analysis showed the mechanisms of diuron toxicity in zebrafish embryos. [ABSTRACT FROM AUTHOR]

Various parameters can influence the toxic response to silver nanoparticles (Ag NPs), including the size and surface properties, as well as the exposure environment and the biological site of action. Herein, we assess the intestinal toxicity of three different sizes (10, 40, and 100 nm) of Ag NPs in embryonic zebrafish, and describe the relationship between the properties and behavior of Ag NPs in the exposure medium, and induction of lethal and sublethal effects. We find that the composition of the medium and the size contribute to differential NPs agglomeration, release of Ag ions, and subsequent effects during exposure. The exposure medium causes dramatic reduction in silver dissolution due to the presence of salts and divalent cations, which limits the lethal potential of silver ions. Lethality is observed primarily for embryos exposed to medium sized Ag NPs (40 nm), but not to the supernatant originated from particles, which suggests that the exposure to particulate silver is the main cause of mortality. On the other hand, the exposure to 10 nm and 100 nm NPs, as well as Ag ions, only causes sublethal developmental defects in skeletal muscles and intestine, and induces a nitric oxide imbalance. Image 1 • Exposure medium composition influences nanosilver toxicity. • Medium-sized silver nanoparticles are more lethal to zebrafish embryos. • In presence of salts, lethality is due primarily to particulate silver. • Exposure to soluble silver is associated with sublethal effects. • Sublethal exposure induces defects and nitrosative stress in the intestine. This study brings new insights to the mechanism of Ag NPs toxicity regarding the physical and experimental factors that cause lethal and sublethal effects during exposure. [ABSTRACT FROM AUTHOR]

Abstract Broad applications and exposure to the fungicide maneb can lead to toxicity in non-target organisms. Maneb is also associated with neurogenerative diseases such as Parkinson's disease (PD). The objectives of this study were to determine the acute toxicity of maneb to zebrafish by measuring mitochondrial bioenergetics, locomotor activity, and the expression of genes related to the oxidative damage response, as well as those related to dopamine signaling due to its association with PD. Zebrafish embryos at 6 h post-fertilization (hpf) were exposed to either solvent control (0.1% DMSO, v / v), or one dose of 0.1, 0.5, 1.0 and 10.0 µM maneb for 96 h. Maneb was moderately toxic to zebrafish embryos, and had a 96-h LC 50 value of 4.29 μM (~ 1.14 mg/L). Maneb induced a dose-dependent increase in mortality, decreased hatching rate, and increased notochord deformity rate at both 1.0 and 10.0 µM after 72 and 96 h. Total body length was also significantly reduced with 1.0 µM maneb. A 50–60% decrease in mean basal oxygen consumption rate was also observed in embryos following a 24 hpf exposure to 10.0 µM maneb but oligomycin-induced ATP production and FCCP-induced maximum respiration remained unaffected. No change was detected in the expression levels of genes associated with oxidative stress (sod1 and sod2), nor those related to dopamine synthesis (th1), dopamine transporter (dat) , dopamine receptors (drd1 , drd2a , drd3 , and drd4b). Thus, modifying the expression of these transcripts may not be a mechanism for maneb-induced developmental toxicity in zebrafish. To assess the potential for neurotoxicity, a dark photokinesis assay was conducted in larvae following 7 d exposure to 0.1, 0.5 and 1.0 μM maneb. Larvae exposed to 0.5 and 1.0 μM maneb showed signs related to hypoactivity, and this reduced activity is hypothesized to be associated with notochord defects as this deformity was prevalent at higher concentrations of maneb. Overall, these data demonstrate that maneb negatively affects embryonic development (i.e. notochord development), affects basal oxygen consumption rates of embryos, and induces hypoactivity in larval fish. This study improves understanding regarding the developmental neurotoxicity of the fungicide maneb to zebrafish. Graphical abstract fx1 Highlights • Developmental neurotoxicity of the fungicide maneb in zebrafish embryos was studied. • Mitochondrial bioenergetics, gene expression, and larval behavior were assessed. • Maneb induced lethality, developmental defects, and notochord deformity at ≥ 1.0 μM. • Exposure to 10.0 μM maneb decreased basal respiration of embryos at 24 h. • Maneb induced hypoactivity in larvae following 7 days exposure to 0.5 and 1.0 μM. [ABSTRACT FROM AUTHOR]

Although numerous studies imply a correlation between chemical contamination and an impaired immunocompetence of wildlife populations, the assessment of immunomodulatory modes of action is currently not covered in the regulatory requirements for the approval of new substances. This is not least due to the complexity of the immune system and a lack of standardised methods and validated biomarkers. To tackle this issue, in this study, the transcriptomic profiles of zebrafish embryos were analysed in response to the immunosuppressive compound clobetasol propionate, a synthetic glucocorticoid, and/or the immunostimulatory compound imiquimod (IMQ), a TLR-7 agonist. Using IMQ, known for its potential to induce psoriasis-like effects in mice and human, this study additionally aimed at evaluating the usability of the zebrafish embryo model as an alternative and 3R conform system for the IMQ-induced psoriasis mouse model. Our study substantiates the suitability of previously proposed genes as possible biomarkers for immunotoxicity, such as socs3, nfkbia, anxa1c, fkbp5 and irg1l. Likewise, however, our findings indicate that these genes may be less suitable to distinguish a suppressive from stimulating fashion of action. In contrast, based on a differential regulation in opposite direction in response to both compounds, krt17, rtn4a, and1, smhyc1 and gmpr were identified as potential novel biomarkers with said power to differentiate. Observed IMQ-induced alterations in the expression of genes previously associated with the pathogenesis of psoriasis such as krt17, nfkbia, parp1, pparg , nfil3–6 , per2, stat4 , klf2 , rtn4a , anxa1c and nr1d2 indicate the inducibility of psoriatic effects in the zebrafish embryo. Our work contributes to the establishment of an approach for a 3R-compliant investigation of immunotoxic mechanisms of action in aquatic vertebrates. The validated and newly identified biomarker candidates of specific immunotoxic effects can be used in future studies in the context of environmental hazard assessment of substances or also for human-relevant immunotoxicological questions. [Display omitted] • Transcriptomic profiles were recorded for a sublethal immune-challenge in zebrafish embryos. • Molecular changes subsequent to imiquimod-induced TLR-7 activation were assessed. • krt17, rtn4a, and1, smhyc1 and gmpr were identified as novel biomarker candidates for immunotoxicity. • The zebrafish embryo may serve as an alternative imiquimod-induced psoriasis model. [ABSTRACT FROM AUTHOR]

As ubiquitous contaminants, nanoplastics and antibiotics are frequently co-presence and widely detected in the freshwater environment and biota, posing a high co-exposure risk to aquatic organisms and even humans. More importantly, how the aging process of nanoplastics affects the joint toxic potential of nanoplastics and antibiotics has not been explored. Here, we generated two aged polystyrene nanoplastics (PS) by UV radiation (UV-PS) and ozonation (O 3 -PS). Non-teratogenic concentrations of pristine PS (80 nm) and antibiotics penicillin (PNC) co-exposure synergistically suppressed the embryo heart beating and behaviors of spontaneous movement, touch response, and larval swimming behavioral response. Pristine PS and aged UV-PS, but not aged O 3 -PS, showed similar effects on zebrafish embryo/larval neurodevelopment. However, when co-exposure with PNC, both aged PS, but not pristine PS, showed antagonistic effects. In late-stage juvenile social behavior testing, we found that PS decreased the exploration in light/dark preference assay. The synergistic effect of aged PS with PNC was further explored, including cellular apoptosis, ROS formation, and neurotransmitter metabolite regulation. Mechanistically, aged UV-PS but not O 3 -PS significantly increased the adsorption rate of PNC compared to pristine PS, which may account for the toxicity difference between the two aged PS. In conclusion, our results confirmed that PS served as a carrier for PNC, and the environmental aging process changed their neurobehavioral toxicity pattern in vivo. [Display omitted] • Pristine PS and aged PS suppress zebrafish embryo/larval neurodevelopment. • PNC co-exposure with aged PS show antagonistic effects. • PNC and aged PS co-exposure decrease the exploration in light/dark preference assay. • PNC and aged PS co-exposure show syngenetic effect on apoptosis and oxidative stress. • PNC and aged PS co-exposure dysregulate neurotransmitter metabolites. [ABSTRACT FROM AUTHOR]

Butylparaben (BuP) is a common antibacterial preservative utilized extensively in food, medical supplies, cosmetics, and personal care products. The current study reports the use of Zebrafish (Danio rerio) embryos to investigate potential developmental toxicity caused by exposure to BuP. The development of Neural crest cells (NCCs) is highly active during gastrulation in Zebrafish embryos. Thus, we utilized 0.5 mg/L, 0.75 mg/L, and 1 mg/L BuP solutions, respectively, in accordance with the international safety standard dosage. We observed severe craniofacial cartilage deformities, periocular edema, cardiac dysplasia, and delayed otolith development in the Zebrafish larvae 5 days after exposure. The oxidative stress response was significantly enhanced. In addition, the biochemical analysis revealed that the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly reduced relative to the control group, whereas the concentration of malondialdehyde (MDA) was significantly elevated. Furthermore, ALP activity, a marker of osteoblast activity, was also reduced. Moreover, the RT-qPCR results indicated that the expression of chondrocyte marker genes sox9a, sox9b, and col2a1a was down-regulated. In addition, the morphology of maxillofacial chondrocytes was altered in Zebrafish larvae, and the proliferation of cranial NCCs was inhibited. Accordingly, our findings indicate that strong oxidative stress induced by BuP inhibits the proliferation of NCCs in larval Zebrafish, leading to craniofacial deformities. • BuP can cause developmental toxicity and craniofacial deformities in zebrafish. • BuP inhibits the proliferation of neural crest cells. • Craniofacial deformities caused by BuP is related to oxidative stress. • BuP injures the craniofacial bone development of non-target species. [ABSTRACT FROM AUTHOR]

The accumulation of antibiotics in the aquatic environment is increasingly becoming a risk to the health of aquatic animal. The purpose of this study was to investigate the acute and chronic toxicity of florfenicol (FF) to zebrafish. A 56-day chronic toxicity test followed a 96-h acute toxicity test. The chronic toxicity test was divided into five FF concentration groups: 0 mg/L (C), 5 mg/L (T5), 10 mg/L (T10), 20 mg/L (T20) and 40 mg/L (T40). Each group had five replicates, with 20 Zebrafish per replicate. The acute toxicity test results showed that the 96 h-LC50 of FF was greater than 2000 mg/L, indicating low toxicity. The exposure concentrations of FF exceeding 20 mg/L can cause oxidative damage to the liver and gill tissues of fish, leading to the accumulation of oxidative products in the tissues and severe damage to antioxidant capacity. The reactive oxygen species (ROS) generated by severe oxidative stress activates the toll like receptors (TLR) pathway, inducing inflammation in the liver and gill tissues, stimulating the upregulation of inflammatory factor expression levels, and leading to immune system disorders. FF exposure at a concentration of 5 mg/L can lead to a significant decrease in the diversity and evenness of gut microbiota. The concentration of FF in water bodies above 37.52 mg/L poses a potential risk to aquatic products. [Display omitted] • The paper conducts research at individual, tissue, cellular, and molecular levels. • We explored the biological toxicity mechanisms of different levels of florfenicol. • The results have great significance for studying the toxicity of antibiotic residues. [ABSTRACT FROM AUTHOR]

The present research examined the environmentally compatible and cost-effective formation of green medicated palladium nanoparticles (EA-PdNPs) utilizing aqueous extracts of Evolvulus alsinoides (EA) and their antibacterial and photocatalytic behaviour. EA aqueous extracts of leaves intervened as a reduction and capping agent. Meanwhile, the physicochemical characteristics and bioactivities of green-treated EA-PdNPs under an alkaline environment remain uncertain. Furthermore, the as-prepared EA-PdNPs seemed to have a face-centered cubic crystal phase with 12 nm particle size, were monodispersed, and demonstrated high stability. The visible region spectra of EA-PdNPs is represented by its optically active area at 426 nm from UV–visible spectroscopy. The chemical state and near surface composition of the EA-PdNPs fabricated from Evolvulus alsinoides leaf extract were clarified using X-ray photoelectron spectroscopy (XPS). Both Gram-positive (+ve) Staphylococcus aureus had zone 20.5 ± 0.5 mm and Gram-negative (-ve) Escherichia coli inhibit zone 22.15 ± 0.2 mm were sensitive to the antibacterial effects of the EA-PdNPs at a concentration of 100 µg/mL. Green-treated EA-PdNPs, on the other hand, were employed as photocatalysts investigators, ultimately resulting in 98% degradation of Rhodamine B dye in 120 min. The outstanding catalytic implementation of all synthesized EA-PdNPs on the photodegradation of the researched pollutants was revealed by UV–visible findings, which examined the decrease in absorption coefficient spectral value within an extremely short time. Furthermore, micro crustacean Daphnia magna and zebrafish (Danio rerio) was successfully used to assess the non-toxicity of EA-PdNPs. The key implications of this findings are that EA-PdNPs toxicity depends on concentration. Our outcomes showed that the EA-PdNPs did not demonstrate considerable toxicity to Daphnia magna at high concentrations (100 µg/L) similarly EA-PdNPs did not showed any significant toxicity on zebrafish (Danio rerio) embryo development at 72 h of post fertilization exposure. Green-treated Pd-NPs produced by Evolvulus alsinoides can be used as probable applicants for biological and clean ecological applications due to their sustainable synthesizing, environmentally friendly, and biocompatibility. [Display omitted] • Green medicated palladium nanoparticles (EA-PdNPs). • Antibacterial activity against both gram -ve and gram +ve. • Photocatalysts degradation resulting in 98% degradation of RhB dye in 120 min. • Daphnia magna and Danio rerio embryo was successfully used to assess the non-toxicity of EA-PdNPs. [ABSTRACT FROM AUTHOR]

Fipronil (FIL) use is currently regulated in several countries due to its specific toxicity to bees. This study investigated the possible developmental toxicities as well as the acute toxicities of FIL, fipronil sulfide (FIL-SI), and fipronil sulfone (FIL-SO) to zebrafish (Danio rerio) embryos. At concentrations up to 5000 μg L−1, FIL- and FIL–SI–treated embryos exhibited significant mortality at 96 h postfertilization. Body length was significantly shortened with increasing concentrations in FIL- and FIL–SI–treated embryos. However, FIL–SO–treated embryos exhibited low mortality with high hatching rates. Body length was also significantly shortened in FIL–SO–treated embryos. Regarding the number of intersegmental vessels (ISVs), all chemical-treated embryos showed high ISV numbers with increasing concentrations of each chemical. FIL and FIL-SI induced abnormal heart formation with heart dysfunction in embryos, whereas FIL-SO did not induce any difference in heart development compared with the control. Abnormal heart formation may be related to the upregulation of nppa responsible for the expression of natriuretic peptides in embryos. Embryonic acetylcholinesterase activity was decreased gradually according to the increase in FIL and FIL-SI concentrations, whereas FIL-SO did not cause any change in enzyme activity. Il-1β responsible for the occurrence of injury or infection was highly upregulated in FIL–SI– and FIL–SO–treated embryos. Therefore, reduction to FIL-SI may be associated with FIL toxicity, whereas oxidation to FIL-SO may be a detoxification route in the environment. [Display omitted] • Fipronil (FIL) and fipronil sulfide (FIL-SI) showed mortality to zebrafish embryos. • FIL, FIL-SI and fipronil sulfone (FIL-SO) caused the shorten body length on embryos. • FIL, FIL-SI, and FIL-SO induced vascular defects in zebrafish embryos. • FIL and FIL-SI inhibited normal cardiac development with decreased heart rates. • Differently expressed c-fos , jun , and il-1β were found in chemical treated embryos. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) exposure is a risk factor for endothelial dysfunction and cardiovascular disease. Ferroptosis is a type of cell death that relies on lipid peroxidation. Whether ferroptosis acts in Cd-induced vascular endothelial damage and the underlying mechanisms remain unclear. Herein, we found that Cd resulted in ferroptosis of vascular endothelial cells (ECs) in vivo and in vitro. In the visualized zebrafish embryos, Cd accumulated in vascular ECs, ROS and lipid peroxidation levels were increased, and the oxidoreductase system was disturbed after exposure. Moreover, Cd decreased Gpx4 in ECs and caused smaller mitochondria with increased membrane density. Accompanied by ferroptosis, the number of ECs and the area of the caudal venous plexus in zebrafish embryos were reduced, and the survival rate of HUVECs decreased. These effects were partially reversed by ferrostatin-1 and aggravated by erastin. Mechanistically, an excessive increase in Heat Shock Protein 70 (Hsp70) was identified by transcriptomics after Cd exposure. Inhibition of Hsp70 by VER-155008 or siRNA ameliorated Cd-induced ferroptosis, thereby alleviating endothelial injury. Furthermore, Hsp70 regulated Cd-induced ferroptosis by targeting multiple targets, including Gpx4, Fth1, Nrf2 and Acsl4. Our findings provide a new approach to investigating the endothelial damage of Cd and indicate that regulation of Hsp70 is an important target for alleviating this process. [Display omitted] • The accumulation of Cadmium in the vessels of zebrafish leads to endothelial damage. • Cadmium-induced endothelial damage relies on ferroptosis. • Cadmium-induced excessive Heat Shock Protein 70 contributes to ferroptosis. • Excessive Heat Shock Protein 70 regulates ferroptosis through multiple targets. [ABSTRACT FROM AUTHOR]

Mirtazapine is a commonly prescribed antidepressant and has been found widespread in aquatic environments. However, its toxicities to aquatic organisms has rarely been explored. Herein, we conducted a comprehensive study on the developmental effects of mirtazapine on early life stages of zebrafish at environmentally relevant concentrations (3.9 ng/L and 43.5 ng/L). Out of the endpoints measured, spontaneous contraction of embryos at 24 h post fertilization (hpf) and hatching rate and heart rate of embryos at 50 hpf and 56 hpf, respectively, were significantly affected. In light-dark transition behavior test, mirtazapine significantly reduced the swimming frequency and swimming speed of embryos at both concentrations of 3.9 ng/L and 43.5 ng/L. Furthermore, the total swimming distances in dark conditions were also significantly reduced. Transcriptomic analysis was further conducted. It demonstrated that the decreased neural activities in embryos may be associated with altered epinephrine and neuregulin signaling. The present results fill a data gap regarding the exposure of fish to mirtazapine at environmentally relevant concentrations and provide new insights into the neurotoxic mechanisms of mirtazapine exposure. [Display omitted] • Mirtazapine significantly affected zebrafish spontaneous contraction and hatching rate. • Mirtazapine led to reduction of zebrafish swimming activities. • Neural behavior impacts may associate with altered epinephrine and neuregulin signaling. [ABSTRACT FROM AUTHOR]

Monoamine oxidase-B (MAO-B), as a principal metabolizing enzyme, plays important roles in the metabolism of catecholamines and xenobiotics in the central nervous system and peripheral tissues. Safinamide, the third-generation reversible MAO-B inhibitor, has potential to alleviate many neurological diseases such as Parkinson's disease (PD) and depression. Exposure to clinical psychotropic drugs often has adverse effects on fetuses. Currently, a variety of studies of safinamide focus on its curative effect and pharmacological effect, while its side effect of embryonic development is barely studied. In this study, we used zebrafish as a model to evaluate the embryonic developmental toxicity of safinamide. Our results revealed that higher concentrations (30 μM) of safinamide treatment caused a decrease in hatching rate and an increase in malformation and mortality in zebrafish larvae. Meanwhile, we observed that lower safinamide exposure (10 μM) increased the body length of zebrafish larvae and resulted in hyperactivity-like behaviors. In addition, an increased trend in dopamine (DA) level was found in 3.3 μM and 10 μM safinamide-exposed groups. Transcriptome analysis identified that safinamide exposure may disturb a variety of physiological processes such as neuroactive ligand-receptor interaction signaling pathway. In summary, our study reveals that safinamide may cause developmental defects in zebrafish larvae and provides insights into its toxic reactions in early develoment. [Display omitted] • Safinamide exposure may cause impaired development and increased body size in zebrafish larvae. • Zebrafish larvae exposed to safinamide exhibited hyperactivity-like behavior. • Enriched neuroactive ligand-receptor interaction pathway was found in zebrafish larvae after safinamide exposure. [ABSTRACT FROM AUTHOR]

During the 20th century, thousands of tons of munitions containing organoarsenic chemical warfare agents (CWAs) were dumped into oceans, seas and inland waters around the world. As a result, organoarsenic CWAs continue to leak from corroding munitions into sediments and their environmental concentrations are expected to peak over the next few decades. There remains, however, a lack of knowledge about their potential toxicity to aquatic vertebrates, such as fish. The aim of this study was to fill in this gap in research, by investigating the acute toxicity of organoarsenic CWAs on fish embryos, using the model species, Danio rerio. To estimate the acute toxicity thresholds of organoarsenic CWAs (Clark I, Adamsite, PDCA), a CWA-related compound (TPA), as well as four organoarsenic CWA degradation products (Clark I[ox], Adamsite[ox], PDCA[ox], TPA[ox]), standardized tests were performed following the OECD no. 236 Fish Embryo Acute Toxicity Test guidelines. Additionally, the detoxification response in D. rerio embryos was investigated by analysing the mRNA expression of five genes encoding antioxidant enzymes (CAT, SOD, GPx, GR and GST). During the 96 h of exposure, organoarsenic CWAs induced lethal effects in D. rerio embryos at very low concentrations (classified as 1st category pollutants according to GHS categorization), and were therefore deemed to be serious environmental hazards. Although TPA and the four CWA degradation products caused no acute toxicity even at their maximum solubility, the transcription of antioxidant-related genes was altered upon exposure to these compounds, indicating the need for further testing for chronic toxicity. Incorporating the results of this study into ecological risk assessments will provide a more accurate prediction of the environmental hazards posed by CWA-related organoarsenicals. • Acute toxicity of organoarsenic chemical warfare agents was tested in Danio rerio. • Clark I, Adamsite and PDCA are several times more acutely toxic than earlier assumed. • The degradation products of the tested compounds are not acutely toxic to fish. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) have been reported to inhibit specification and differentiation of erythroid cells, chromatophores, and myofibrils during zebrafish embryogenesis. However, the knowledge of biological effects of AgNPs on eye development, especially on lens development is scarce. In this study, embryos were exposed to or injected with 0.4 mg/L AgNPs, and the results indicate that no obvious morphological changes in eye formation were observed in the stressed embryos compared to the controls. However, clefts and vacuoles were observed in lens of embryos from AgNPs stressed group. Additionally, the down-regulated expressions of different lens crystallin isoform genes and the normal expression of retinal genes were observed in AgNPs stressed embryos, suggesting AgNPs might inhibit the development of lens rather than the development of retina in zebrafish embryos. Moreover, no obvious cell apoptosis was observed, but normal nuclear DNA and RNA export was observed in lens cells. Together, the data in this study reveal that AgNPs damage the development of lens rather than retina resulting in eye abnormalities via some unknown mechanisms rather than via triggering cells apoptosis or blocking nuclear DNA or RNA export. [ABSTRACT FROM AUTHOR]

Several studies have suggested that air pollutants combine exposure have greater adverse effects. However, limited studies were available on the combined toxicity of silica nanoparticles (SiNPs) and benzo[ a ]pyrene (B[ a ]P). The study was to evaluate the toxic effect and mechanisms of low-dose exposure of SiNPs, B[ a ]P and co-exposure in zebrafish embryos. In this study, zebrafish embryos received intravenous microinjection of SiNPs and B[ a ]P, and then was used to select differentially expressed genes by microarray analysis. Multiple bioinformatics analyses and STC analysis were done to identify key genes, pathways and biological processes and the expression trend of genes in each group. 1) 3065 differentially expressed genes were identified in zebrafish embryos. 2) These differentially expressed genes were involved in multiple biological processes and cellular processes such as immunity, response to stimuli, cell proliferation, adhesion, signaling transduction, and embryonic development. 3) Dynamic Gene Network analysis was used to identify a subgroup of 26 core genes that involved in multiple biological processes and cellular processes. 4) Pathway analysis and Signal-net analysis indicated that the MAPK signaling pathway, calcium signaling pathway, p53 signaling pathway, PI3k/Akt signaling pathway, and several pathways associated with immune response were the most prominent significant pathways induced by co-exposure of SiNPs and B[ a ]P in zebrafish embryos. Our study demonstrated that the molecular actions of co-treated with SiNPs and B[ a ]P on the immune system, inflammatory process and cardiovascular development had more severe toxicity than single exposure. [ABSTRACT FROM AUTHOR]

Abstract Flutolanil, an amide fungicide, had been detected frequently in aquatic environments; it is thus potentially a great risk to aquatic organisms and human health. Therefore, we investigated the developmental toxicity and the potential mechanism of thyroid endocrine disruption induced by flutolanil based on 1H NMR metabolomics analysis using a zebrafish model. Hatching of zebrafish embryo exposed to flutolanil was inhibited at 72 hpf (hour post-fertilization) and survival and body length at 96 hpf. In addition, increased teratogenic effects on embryos were observed, including pericardial edema, spine deformation, and tail malformation. Furthermore, flutolanil induced slower heartbeat and larger pericardial area in the treated groups than control group. Transcription levels of TRH , TSHR , TPO , Dio1 , TRα , and UGT1ab were significantly altered after flutolanil exposure. Metabolomics analysis further indicated that flutolanil induced alterations of energy, amino acids, nucleotide, lipids, and fatty acid metabolism. Our study also indicated that flutolanil exposure led to alterations of endogenous metabolites, which induced the thyroid endocrine disruption in zebrafish. Ultimately, embryonic developmental toxicity was caused by flutolanil. Graphical abstract Image 1 Highlights • Flutolanil induced cardiac effect, spine and tail deformation in zebrafish embryos. • Flutolanil exposure induced thyroid endocrine disruption in zebrafish embryos. • Flutolanil exposure increased the level of thyroid hormones. • Flutolanil exposure altered genes expression in the HPT axis in zebrafish embryos. • Metabolism pathways disturbance in embryos were observed after flutolanil exposure. Flutolanil exposure led to alterations of endogenous metabolites, which induced developmental toxicity and thyroid disruption in zebrafish. [ABSTRACT FROM AUTHOR]

In the area of medical imaging, automation of medical image classification or recognition is an active field of research. Over the past decade, due to the popularity and usability of artificial neural networks, it is becoming the norm to achieve this automation by deep neural networks. In toxicology based research, zebrafish has become a key model organism in phenotypical imaging and drug discovery. Detection of complex patterns and phenotypes in zebrafish embryo during preclinical or clinical trials is a standard part of the drug discovery cycle. Currently this classification task of phenotypes is mostly experts based. In this work, we propose a fine-tuned convolution neural network (CNN) based model for automated classification of different phenotypical changes observed due to the toxic substance in the zebrafish embryo. We demonstrated the ability of CNN model as well as a fine-tuned CNN based model to classify different deformation in an embryo with high accuracy. Such automated medical imaging model can be used extensively by experts in the area of toxicology and drug discovery. [ABSTRACT FROM AUTHOR]

Illicit drugs have been identified as emerging aquatic pollutants because of their widespread presence in freshwaters and potential toxicity towards aquatic organisms. Among illicit drug residues, cocaine (COC) and its main metabolites, namely benzoylecgonine (BE) and ecgonine methyl ester (EME), are commonly detected in freshwaters worldwide at concentration that can induce diverse adverse effects to non-target organisms. However, the information of toxicity and mechanisms of action (MoA) of these drugs, mainly of COC metabolites, to aquatic species is still fragmentary and inadequate. Thus, this study was aimed at investigating the toxicity of two concentrations (0.3 and 1.0 μg/L) of COC, BE and EME similar to those found in aquatic ecosystems on zebrafish ( Danio rerio ) embryos at 96 h post fertilization through a functional proteomics approach. Exposure to COC and both its metabolites significantly altered the protein profile of zebrafish embryos, modulating the expression of diverse proteins belonging to different functional classes, including cytoskeleton, eye constituents, lipid transport, lipid and energy metabolism, and stress response. Expression of vitellogenins and crystallins was modulated by COC and both its main metabolites, while only BE and EME altered proteins related to lipid and energy metabolism, as well as to oxidative stress response. Our data confirmed the potential toxicity of low concentrations of COC, BE and EME, and helped to shed light on their MoA on an aquatic vertebrate during early developmental period. [ABSTRACT FROM AUTHOR]

Hydraulic fracturing to extract oil and natural gas reserves is an increasing practice in many international energy sectors. Hydraulic fracturing flowback and produced water (FPW) is a hyper saline wastewater returned to the surface from a fractured well containing chemical species present in the initial fracturing fluid, geogenic contaminants, and potentially newly synthesized chemicals formed in the fracturing well environment. However, information on FPW toxicological mechanisms of action remain largely unknown. Both cardiotoxic and respirometric responses were explored in zebrafish ( Danio rerio ) embryos after either an acute sediment-free (FPW-SF) or raw/sediment containing (FPW-S) fraction exposure of 24 and 48 h at 2.5% and 5% dilutions. A 48 h exposure to either FPW fraction in 24–72 h post fertilization zebrafish embryos significantly increased occurrences of pericardial edema, yolk-sac edema, and tail/spine curvature. In contrast, larval heart rates significantly decreased after FPW fraction exposures. FPW-S, but not FPW-SF, at 2.5% doses significantly reduced embryonic respiration/metabolic rates (MO 2 ), while for 5% FPW, both fractions reduced MO 2 . Expression of select cardiac genes were also significantly altered in each FPW exposure group, implicating a cardiovascular system compromise as the potential cause for reduced embryonic MO 2 . Collectively, these results support our hypothesis that organics are major contributors to cardiac and respiratory responses to FPW exposure in zebrafish embryos. Our study is the first to investigate cardiac and respiratory sub-lethal effects of FPW exposure, demonstrating that FPW effects extend beyond initial osmotic stressors and verifies the use of respirometry as a potential marker for FPW exposure. [ABSTRACT FROM AUTHOR]

Although bisphenol A (BPA) is commonly recognized as an endocrine disruptor, the metabolic consequences of its exposure are still poorly understood. In this study, we present a non-targeted LC-MS based metabolomic analysis in combination with a full-genome, high-throughput RNA sequencing (RNA-Seq) to reveal the metabolic effects and the subjacent regulatory pathways of exposing zebrafish embryos to BPA during the first 120 hours post-fertilization. We applied multivariate data analysis methods to extract biochemical information from the LC-MS and RNA-Seq complex datasets and to perform testable predictions of the phenotypic adverse effects. Metabolomic and transcriptomic data revealed a similar subset of altered pathways, despite the large difference in the number of identified biomarkers (around 50 metabolites and more than 1000 genes). These results suggest that even a moderate coverage of zebrafish metabolome may be representative of the global metabolic changes. These multi- omic responses indicate a specific metabolic disruption by BPA affecting different signaling pathways, such as retinoid and prostaglandin metabolism. The combination of transcriptomic and metabolomic data allowed a dynamic interpretation of the results that could not be drawn from either single dataset. These results illustrate the utility of -omic integrative analyses for characterizing the physiological effects of toxicants beyond the mere indication of the affected pathways. [ABSTRACT FROM AUTHOR]

Microcystin-LR (MCLR) has been reported to cause developmental neurotoxicity in zebrafish, but there are few studies on the mechanisms of MCLR-induced transgenerational effects of developmental neurotoxicity. In this study, zebrafish were exposed to 0, 1, 5, and 25 μg/L MCLR for 60 days. The F1 zebrafish embryos from the above-mentioned parents were collected and incubated in clean water for 120 h for hatching. After examining the parental zebrafish and F1 embryos, MCLR was detected in the gonad of adults and F1 embryos, indicating MCLR could potentially be transferred from parents to offspring. The larvae also showed a serious hypoactivity. The contents of dopamine, dihydroxyphenylacetic acid (DOPAC), serotonin, gamma-aminobutyric acid (GABA) and acetylcholine (ACh) were further detected, but only the first three neurotransmitters showed significant reduction in the 5 and 25 μg/L MCLR parental exposure groups. In addition, the acetylcholinesterase (AChE) activity was remarkably decreased in MCLR parental exposure groups, while the expression levels of manf , bdnf , ache , htr1ab , htr1b , htr2a , htr1aa , htr5a , DAT , TH1 and TH2 genes coincided with the decreased content of neurotransmitters (dopamine, DOPAC and serotonin) and the activity of AChE. Neuronal development related genes, α1-tubulin , syn2a , mbp , gfap , elavl3 , shha and gap43 were also measured, but gap43 was the gene only up-regulated. Our results demonstrated MCLR could be transferred to offspring, and subsequently induce developmental neurotoxicity in F1 zebrafish larvae by disturbing the neurotransmitter systems and neuronal development. [ABSTRACT FROM AUTHOR]

Paroxetine (PRX) is a common antidepressant drug which widely existence in natural environment. Numerous studies in the past few decades have focused on the beneficial effects of PRX on depression, however, the toxic properties and the potential mechanisms remain unclear. In this study, zebrafish embryos were exposed to 1.0, 5.0, 10 and 20 mg/L of PRX from 4 to 120-hour-post-fertilization (hpf), and it showed that PRX exposure caused adverse effects in zebrafish embryos, including decreased body length, blood flow velocity, cardiac frequency, cardiac output and increased burst activity and atria area. Meanwhile, the Tg (myl7: EGFP) and Tg (lyz: DsRed) transgenic zebrafish were used to detect the cardiotoxicity and inflammation response of PRX. Moreover, the heart development associated genes (vmhc, amhc, hand2, nkx2.5, ta, tbx6, tbx16 and tbx20) and inflammatory genes (IL-10, IL-1β, IL-8 and TNF-α) were up-regulated after PRX challenge. In addition, Aspirin was used to alleviate the PRX-induced heart development disorder. In conclusion, our study verified the PRX induced inflammatory related cardiotoxicity in larva zebrafish. Meanwhile, the current study shown the toxic effects of PRX in aquatic organism, and provide for the environmental safety of PRX. [Display omitted] • Paroxetine (PRX) is widely existence in aquatic environment. • PRX induced the cardiac toxic effect in larva zebrafish. • Inflammatory and cardiac developmental related genes were increased by PRX. • Inflammation response is the potential mechanism of PRX induced cardiac disorder. [ABSTRACT FROM AUTHOR]

Polyglycolic acid (PGA) is an emerging biodegradable plastic material. Together with polylactic acid (PLA), PGA is considered a suitable alternative to conventional plastics and has been widely used in biomedical and food packaging industries. However, degradable plastics continue to face the drawbacks of harsh degradation environment and long degradation time, and may harm the environment and the human body. Therefore, our study focused on assessing the effects of degradable microplastics PGA and PLA on the development and neurobehavior of zebrafish. The results showed that PGA and PLA had little effect on 3–10 hpf embryos. However, developmental stunting was observed in a100 mg/L PGA and PLA-exposed group at 24 hpf. In addition, PGA and PLA exposure decreased the survival and hatching rates, increased wakefulness, and reduced sleep in zebrafish. This indicates that PGA and PLA may affect the circadian behavior of zebrafish by affecting the brain–derived neurotrophic factor (BDNF). Therefore, our results suggest that PGA and PLA exposure induces developmental toxicity, reduces voluntary locomotion, induces of anxiety–like behaviors, and impairs sleep/wake behaviors in zebrafish larvae. This also suggests that the potentially toxic effects of degradable plastics cannot be ignored and that the biological effects of PGA require further research. [Display omitted] • PGA and PLA caused a delay in early larval development and led to mortality. • PGA and PLA damaged the motility of larvae, while PLA caused anxiety- like behavior. • PGA and PLA may influence the sleep/wake behavior of larvae by affecting bdnf. • 7,8-DHF partially alleviated the adverse effects caused by PGA and PLA. [ABSTRACT FROM AUTHOR]

Nanoparticle (NP) surface coatings are known to influence the toxicity of engineered nanomaterials. This work examines the effect of glycine functionalization on silica NPs and investigates changes in viability and developmental defects in the organs of zebrafish embryos upon exposure. Silica NPs and glycine-functionalized silica NPs are synthesized and characterized. Exposure of zebrafish embryos to glycine-silica NPs affects the mortality percentage in a similar manner to soluble glycine. Developmental defects are observed in embryos exposed to soluble glycine, glycine-silica NPs, or silica NPs in comparison with the unexposed embryos. The damage is localized in the brain, heart, and liver of zebrafish embryos. These observations suggest a complex mechanism of toxicity, with glycine maintaining its toxic activity even when covalently bound on silica surface. Our results illustrate that surface modification of non-lethal particles can create different toxicity outcomes in the organs of exposed zebrafish embryos. [ABSTRACT FROM AUTHOR]