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1.
Chemosphere ; 239: 124802, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31521933

RESUMO

Pesticides are usually present as mixtures in water environments. Evaluating the toxic effects of individual pesticide may not be enough for protecting ecological environment due to interactions among substances. In this study, we aimed to examine the lethal doses and gene expression changes in zebrafish (Danio rerio) upon exposure to individual and mixture pesticides [malathion (MAL), chlorpyrifos (CHL) and lambda-cyhalothrin (LCY)]. Individual pesticide toxicity evaluation manifested that the toxicity of the three pesticides to D. rerio at various developmental stages (embryonic, larval, juvenile and adult stages) followed the order of LCY > CHL > MAL. On the contrary, the least toxicity to the animals was discovered from MAL. Most of the tested pesticides displayed lower toxicities to the embryonic stage compared with other life stages of zebrafish. Synergistic effects were monitored from two binary mixtures of LCY in combination with MAL or CHL and ternary mixture of MAL + CHL + LCY. The expressions of 16 genes involved in oxidative stress, immunity system, cell apoptosis and endocrine disruption at the mRNA level revealed that embryonic zebrafish were influenced by the individual or mixture pesticides. The expressions of Tnf, P53, TRα, Crh and Cyp19a exerted greater variations upon exposure to pesticide mixtures compared with their individual compounds. Collectively, the transcriptional responses of these genes might afford early warning biomarkers for identifying pollutant exposure, and the data acquired from this study provided valuable insights into the comprehensive toxicity of pesticide mixtures to zebrafish.


Assuntos
Misturas Complexas/toxicidade , Larva/efeitos dos fármacos , Praguicidas/toxicidade , Animais , Clorpirifos/toxicidade , Interações de Medicamentos , Disruptores Endócrinos/toxicidade , Estágios do Ciclo de Vida/efeitos dos fármacos , Malation/toxicidade , Nitrilos/toxicidade , Piretrinas/toxicidade , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
2.
Chemosphere ; 239: 124754, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726531

RESUMO

We conducted the ecological risk assessment in an urban stream by using multiple-level approaches ranging from community level, chemical analyses in water and sediments, physiological assays of DNA biomarkers, embryonic development tests, and gene-level marker analyses of cyp1a, c-Fos, CRH, transgenic fli1:GFP and HuC:eGFP in zebrafish (Danio rerio). In water, the chemical perturbations based on nutrients (N,P), organic matter, ionic contents and metals identified in downstream zone. Analogous corroborations verified in sediment samples having hazardous metals (Zn, Pb, Cu, Ni, As, Cd). The chemical contaminations reflected significant damages in fish DNA, based on tDNA, tail length (TL), and tail extent moment (TEM). Zebrafish embryonic development experiments significantly enlightened the chemical contaminants in downstream compared to those in control and reference conditions. Hatching and survival rates rigorously declined in downstream region. Embryonic development delayed and followed by death in the downstream substantiated by the above-mentioned findings. Similar were the findings on heart rate and pigmentation largely affected in the contaminated zone. Pollutants in urban stream reflected significantly at the gene level, and were corroborated through experiments using transgenic zebrafish strains that were influenced by pollutants during the process of occurrence. In conclusion, these studies illuminate the community to gene-level ecological health assessment that could be useful for ecological risk assessments of urban streams and rivers. Further, the gene-level biomarkers and transgenic zebrafish experiments combination propose the procedures could be effectively used as sensitive and efficient biomarkers of ecological health and risk assessment in urban streams from community to gene-level assessments.


Assuntos
Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Metais Pesados/toxicidade , Compostos Orgânicos/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Biomarcadores/análise , Dano ao DNA/efeitos dos fármacos , Ecologia , Metais Pesados/análise , Compostos Orgânicos/análise , Medição de Risco , Rios/química , Poluentes Químicos da Água/análise
3.
Chemosphere ; 240: 124948, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726616

RESUMO

Zearalenone is a xenoestrogenic mycotoxin produced by Fusarium species. High exposure with zearalenone induces reproductive disorders worldwide. Cyclodextrins are ring-shaped host molecules built up from glucose units. The apolar cavity of cyclodextrins can entrap so-called guest molecules. The formation of highly stable host-guest type complexes with cyclodextrins can decrease the biological effect of the guest molecule. Therefore, cyclodextrins may be suitable to decrease the toxicity of some xenobiotics even after the exposure. In this study, the protective effect of beta-cyclodextrins against zearalenone-induced toxicity was investigated in HeLa cells and zebrafish embryos. Fluorescence spectroscopic studies demonstrated the formation of stable complexes of zearalenone with sulfobutyl-, methyl-, and succinyl-methyl-substituted beta-cyclodextrins at pH 7.4 (K = 1.4-4.7 × 104 L/mol). These chemically modified cyclodextrins considerably decreased or even abolished the zearalenone-induced loss of cell viability in HeLa cells and mortality in zebrafish embryos. Furthermore, the sublethal effects of zearalenone were also significantly alleviated by the co-treatment with beta-cyclodextrins. To test the estrogenic effect of the mycotoxin, a transgenic bioindicator zebrafish model (Tg(vtg1:mCherry)) was also applied. Our results suggest that the zearalenone-induced vitellogenin production is partly suppressed by the hepatotoxicity of zearalenone in zebrafish. This study demonstrates that the formation of stable zearalenone-cyclodextrin complexes can strongly decrease or even abolish the zearalenone-induced toxicity, both in vitro and in vivo. Therefore, cyclodextrins appear as promising new mycotoxin binders.


Assuntos
Substâncias Protetoras/farmacologia , Zearalenona/toxicidade , Peixe-Zebra/embriologia , beta-Ciclodextrinas/farmacologia , Animais , Ciclodextrinas/química , Estrogênios/farmacologia , Células HeLa/efeitos dos fármacos , Humanos , Micotoxinas/metabolismo , Substâncias Protetoras/química , Reprodução/efeitos dos fármacos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismo
4.
Sci Total Environ ; 702: 134703, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31733549

RESUMO

Cardiovascular agents are among the most frequently prescribed pharmaceuticals worldwide. They are widely detected in aquatic ecosystems, while their ecotoxicological implications are rarely explored. Here, by the use of a new developed high-throughput zebrafish embryo screening approach, we systematically assessed the cardiovascular disruptive effects of 32 commonly used cardiovascular agents at environmental relevant concentrations and above (0.04, 0.2 and 1 µM). Multiple endpoints, including cardiac output, heart rate and blood flow, were quantified via customized video analysis approaches. Among the 32 agents, simvastatin and lovastatin exhibited the strongest toxicities to fish embryos, and the lethal doses were observed at 0.2 µM and 1 µM. Beta-blockers such as atenolol and metoprolol significantly decreased heart rates by up to 15% and 12% and increased blood flows by up to 14% and 14%, respectively, at concentrations as low as 0.04 µM. Several hypertension/hyperlipidemia medications such as pravastatin and enalapril led to significant inhibition of heart rates (up to 14% and 16% decreases, respectively) as well as slightly decreases of the cardiac outputs and blood flows. In addition, a tentative risk assessment clearly demonstrated that some compounds such as atenolol, metoprolol and bezafibrate pose considerable risks to aquatic organisms at environmental or slightly higher than surface water concentrations. Our results provided novel insights into understanding of the potential risks of cardiovascular agents and contributed to their environmental hazard ranking.


Assuntos
Fármacos Cardiovasculares/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Atenolol , Ecotoxicologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/fisiologia , Metoprolol , Medição de Risco
5.
Ecotoxicol Environ Saf ; 188: 109870, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31683046

RESUMO

BPF, a substitute of BPA, has been widely detected in environment and human bodies. Although the genotoxicity, endocrine disrupting effects, reproductive toxicity of BPF has been well documented, its neurodevelopmental toxicity still remains nebulous. In our study, zebrafish embryos were exposed to BPF treatment (0, 7, 70 and 700 µg/L) for 3 or 6 days. Our results showed that BPF exposure markedly decreased zebrafish locomotor behavior, increased oxidative stress, promoted apoptosis and altered brain structure in zebrafish. In addition, the expressions of neurodevelopment related genes were also downregulated upon BPF treatment. In conclusion, our results systematically demonstrated the developmental neurotoxicity of BPF in zebrafish.


Assuntos
Compostos Benzidrílicos/toxicidade , Encéfalo/efeitos dos fármacos , Fenóis/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Apoptose/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Exposição Ambiental , Feminino , Locomoção/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra/crescimento & desenvolvimento
6.
Sci Total Environ ; 700: 134867, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31706091

RESUMO

Different studies have reported the ecotoxicological effects of polyethylene microplastics (PE MPs) on aquatic organisms; however, little is known about their toxicity in the early life stages of aquatic vertebrates living in freshwater ecosystems. Thus, the aim of the current study is to evaluate the toxicity of PE MPs throughout the development of Danio rerio after their static and semi-static exposure to different concentrations of these pollutants (6.2, 12.5, 25, 50 and 100 mg/L) - models were monitored at different time-periods, namely: 24, 48, 72, 96, 120 and 144 h. Based on the collected data, small PE MP concentrations have harmful effects on D. rerio embryos and larvae; the magnitude and characteristics of these effects depend on the adopted exposure system, which can be static or semi-static. PE MPs had negative effect on embryos' hatching rate in both exposure systems. However, the early hatching observed during the exposure through the static system could explain the lower larval survival rate after egg hatching. Nevertheless, PE MPs induced significant changes in various morphometric parameters. The present study is the first to assess the addressed topic; therefore, it is recommended to carry out future investigations to broaden the knowledge about PE MP toxicity.


Assuntos
/toxicidade , Polietileno/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Organismos Aquáticos , Embrião não Mamífero , Peixe-Zebra/embriologia
7.
Sci Total Environ ; 701: 134870, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31726413

RESUMO

Deltamethrin (DM) is a widely used insecticide and reveals neural, cardiovascular and reproductive toxicity to various aquatic organisms. It has been known that DM negatively affects motion of zebrafish (Danio rerio). However, little is known in relation to the impacts of DM on development of swim bladder, which is a key organ for motion. In the present study, zebrafish embryos were exposed to 20 and 40 µg/L DM. The changes of swim bladder morphology were observed and transcription levels of key genes were compared between DM treatments and the control. The results showed that DM treatments significantly blocked the formation of progenitor and tissue layers in swim bladder of zebrafish embryos, leading to failed inflation of swim bladder. Compared with the control, the key genes (pbx1, foxA3, mnx1, has2, anxa5b, hprt1l and elovl1a) responsible for swim bladder development also showed decreased levels in response to DM treatments, suggesting that DM might specifically affect swim bladder development. Moreover, transcription levels of genes in the Wnt (wnt5b, tcf3a, wnt1, wnt9b, fzd1, fzd3 and fzd5) and Hedgehog (ihhb, ptc1 and ptc2) signaling pathways all decreased significantly in response to DM treatments, compared with the control. Considering the importance of Wnt and Hedgehog pathways in development of swim bladder, these results suggested that DM might affect swim bladder development through inhibiting the Wnt and Hedgehog pathways. Overall, the present study reported that swim bladder might be a potential target organ of DM toxicity in zebrafish, which contributed more information to the evaluation of DM's environmental risks.


Assuntos
Sacos Aéreos/crescimento & desenvolvimento , Inseticidas/toxicidade , Nitrilos/toxicidade , Piretrinas/toxicidade , Peixe-Zebra/embriologia , Sacos Aéreos/efeitos dos fármacos , Animais , Embrião não Mamífero
8.
Chemosphere ; 240: 124936, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31568941

RESUMO

Triphenyltin (TPT) is widely used and commonly found in a water environment, so its effects on aquatic systems are of great concern. This study aimed to reveal the effects of chronic parental exposure of TPT on thyroid disruption and growth inhibition in zebrafish. Adult zebrafish (F0 generation) were exposed to environmentally relevant concentrations (1, 10, and 100 ng/L) of TPT for 60 days, and the larvae (F1 generation) were tested without TPT treatment. Results demonstrated that parental exposure to TPT disrupts thyroid function in zebrafish offspring: serum thyroxine (T4) significantly decreased, while serum 3,5,3'-triiodothyronine (T3) increased, and several genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were down-regulated. In addition, we observed developmental abnormalities in the larvae, demonstrated by a significantly altered hatching rate, malformation rate, body length, heart rate, and survival rate, as well as down-regulation of genes involved in the growth hormone/insulin-like growth factor (GH/IGF) axis. Therefore, parental exposure to TPT induces toxicity in fish offspring through perturbation of the HPT and GH/IGF axes.


Assuntos
Larva/crescimento & desenvolvimento , Compostos Orgânicos de Estanho/toxicidade , Praguicidas/toxicidade , Glândula Tireoide/patologia , Poluentes Químicos da Água/toxicidade , Animais , Feminino , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Larva/efeitos dos fármacos , Masculino , Exposição Materna/efeitos adversos , Exposição Paterna/efeitos adversos , Somatomedinas/genética , Somatomedinas/metabolismo , Glândula Tireoide/efeitos dos fármacos , Tiroxina/sangue , Tri-Iodotironina/sangue , Peixe-Zebra/embriologia
9.
Chemosphere ; 238: 124653, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31473528

RESUMO

Discharge of heated effluent at 8-12 °C above ambient into water areas is known to retard the growth of aquatic organisms due to heat stress. Nucleotide excision repair (NER) maintains genome integrity by removing helix-distorting adducts such as UV-induced DNA lesions. This study explored how NER in zebrafish (Danio rerio) embryos at different hours post fertilization (hpf) responded to + 8.5 °C heat shock for 30 min. Our transcription-based repair assay monitoring the ability of zebrafish extracts to upregulate a UV-suppressed gene expression detected a 2-fold increase of NER capacity in 10 hpf early embryos after heat stress. In contrast, heat stress caused a mild inhibition of NER capacity in 24 hpf mid-early embryos. Heat-treated and untreated 10 hpf zebrafish extracts displayed similar levels of UV-damaged-DNA binding activities, while an apparently weaker (6-4) photoproduct (6-4 PP) binding activity was present in heat-stressed 24 hpf zebrafish extracts. Heat stress enhanced UV-induced NER in 10 hpf embryos by increasing the efficiency of damage incision/excision based on both genomic DNA electrophoresis and terminal deoxytransferase (TdT)-mediated end labeling assay. UV-irradiated embryos preexposed to heat stress produced a significantly larger amount of NER-associated DNA fragments about 20-30 nucleotides in length than embryos only heat-treated or irradiated. Correlated with its inhibitory effect on 6-4 PP damage recognition, heat stress downregulated damage incision/excision activities in 24 hpf embryos. Hence, thermal stress may positively or negatively modulate NER capacity in zebrafish embryos at different stages by targeting at the step of DNA incision/excision or damage recognition.


Assuntos
Dano ao DNA , Reparo do DNA , Resposta ao Choque Térmico/genética , Raios Ultravioleta/efeitos adversos , Peixe-Zebra/genética , Animais , DNA/metabolismo , Embrião não Mamífero/metabolismo , Expressão Gênica , Fatores de Tempo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética
10.
Chemosphere ; 238: 124587, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31425864

RESUMO

Pharmaceuticals are emerging as environmentally problematic compounds. As they are often not appropriately removed by sewage treatment plants, pharmaceutical compounds end up in surface water environments worldwide at concentrations in the ng to µg L-1 range. There is a need to further explore single compound and mixture effects using e.g. in vivo test model systems. We have investigated, for the first time, behavioral effects in larval zebrafish (Danio rerio) exposed to a binary mixture of an antidepressant drug (citalopram) and a synthetic opioid (tramadol). Citalopram and tramadol have a similar mode of action (serotonin reuptake inhibition) and are known to produce drug-drug interactional effects resulting in serotonin syndrome (SS) in humans. Zebrafish embryo-larvae were exposed to citalopram, tramadol and 1:1 binary mixture from fertilization until 144 h post-fertilization. No effects on heart rate, spontaneous tail coiling, or death/malformations were observed in any treatment at tested concentrations. Behavior (hypoactivity in dark periods) was on the other hand affected, with lowest observed effect concentrations (LOECs) of 373 µg L-1 for citalopram, 320 µg L-1 for tramadol, and 473 µg L-1 for the 1:1 mixture. Behavioral EC50 was calculated to be 471 µg L-1 for citalopram, 411 µg L-1 for tramadol, and 713 µg L-1 for the 1:1 mixture. The results of this study conclude that tramadol and citalopram produce hypoactivity in 144 hpf zebrafish larvae. Further, a 1:1 binary mixture of the two caused the same response, albeit at a higher concentration, possibly due to SS.


Assuntos
Analgésicos Opioides/farmacologia , Citalopram/farmacologia , Inibidores de Captação de Serotonina/farmacologia , Tramadol/farmacologia , Poluentes Químicos da Água/farmacologia , Peixe-Zebra/embriologia , Animais , Embrião não Mamífero/efeitos dos fármacos , Larva/efeitos dos fármacos
11.
Chemosphere ; 238: 124753, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31545217

RESUMO

Boscalid is a widely used fungicide in agriculture and has been frequently detected in both environments and agricultural products. However, evidence on the neurotoxic effect of boscalid is scarce. In this study, zebrafish served as an animal model to investigate the toxic effects and mechanisms of boscalid on aquatic vertebrates or higher animals. And we unravelled that boscalid induced developmental defects associated with oxidative stress. Developmental defects, including head deformity, hypopigmentation, decreased number of newborn neurons, structural defects around the ventricle, enlarged intercellular space in the brain, and nuclear concentration, were observed in zebrafish embryos after boscalid exposure at 48 hpf. Interestingly, we found that boscalid might directly induce oxidative stress and alter the activity of ATPase, which in turn disrupted the expression of genes involved in neurodevelopment and transmitter-transmitting signalings and melanocyte differentiation and melanin synthesis signalings. Ultimately, the differentiation of nerve cells and melanocytes were both impacted and the synthesis of melanin was inhibited, leading to morphological abnormalities. Additionally, exposure to boscalid led to less and imbalance motion and altered tendency of locomotor in larval fish. Collectively, our results provide new evidences for a comprehensive assessment of its toxicity and a warning for its residues in environment and agricultural products.


Assuntos
Compostos de Bifenilo/toxicidade , Fungicidas Industriais/toxicidade , Larva/efeitos dos fármacos , Niacinamida/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Embrião não Mamífero/efeitos dos fármacos , Humanos , Melaninas/biossíntese , Melanócitos/citologia , Neurônios/citologia , Síndromes Neurotóxicas/patologia , Niacinamida/toxicidade , Peixe-Zebra/metabolismo
12.
Environ Pollut ; 255(Pt 2): 113328, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31671316

RESUMO

As a widely used organotin acaricide nowadays, azocyclotin (ACT) could induce thyroidal endocrine disruption in fishes and amphibians, but its dominant disrupting mode remains unknown. In this study, zebrafish were firstly exposed to ACT (0.18-0.36 ng/mL) from 2 hpf (hours post fertilization) to 30 dpf (days post fertilization), and a series of developmental toxicological endpoints and thyroid hormones were measured. Result showed that no developmental toxicity to zebrafish was found in 0.18 and 0.24 ng/mL groups except decreased body weight (30 dpf, 0.24 ng/mL). However, exposed to 0.36 ng/mL ACT led to reductions in heartbeat (48 hpf), hatching rate (72 hpf) and bodyweight (30 dpf). General tendencies of decreases in free T3 but increases in free T4 and reductions in ratio of free T3/T4 were also found, inferring that type II deiodinase (Dio2) was repressed. This inference was confirmed by Western analysis that Dio2 expression reduced by 42.7% after 0.36 ng/mL ACT treatment. Moreover, RNA-Seq analysis implied that exposed to 0.36 ng/mL ACT altered the genome-wide gene expression profiles of zebrafish. Totally 5660 genes (involving 3154 down-regulated and 2596 up-regulated genes) were differentially expressed, and 13 deferentially expressed genes including down-regulated dio2 were significantly enriched in thyroid hormone signaling pathway. Subsequently, an in vitro thyroid receptor-reporter gene assay using GH3 cells was performed to further explore the potential disrupting mechanism. Result showed that luciferase activity slightly increased after exposure to ACT alone or ACT combined with low level T3, but was suppressed when combined with high level T3. It indicted there probably existed a competitive relationship in some extent between ACT and T3 in vivo. Overall, the present study provided preliminary evidences that long-term exposure to trace ACT repressed Dio2 expression, declined T3 and then activated thyroid receptor-mediated signaling, thereby leading to integrated thyroid endocrine disruption in zebrafish larvae.


Assuntos
Disruptores Endócrinos/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Iodeto Peroxidase/metabolismo , Compostos Orgânicos de Estanho/toxicidade , Glândula Tireoide/metabolismo , Tri-Iodotironina/biossíntese , Animais , Linhagem Celular , Larva/metabolismo , Transdução de Sinais/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Peixe-Zebra/embriologia
13.
Analyst ; 144(24): 7192-7199, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31696868

RESUMO

The magic angle coil spinning (MACS) technique has been introduced as a very promising extension for solid state NMR detection, demonstrating sensitivity enhancements by a factor of 14 from the very first time it has been reported. The main beneficiary of this technique is the scientific community dealing with mass- and volume-limited, rare, or expensive samples. However, more than a decade after the first report on MACS, there is a very limited number of groups who have continued to develop the technique, let alone it being widely adopted by practitioners. This might be due to several drawbacks associated with the MACS technology until now, including spectral linewidth, heating due to eddy currents, and imprecise manufacturing. Here, we report a device overcoming all these remaining issues, therefore achieving: (1) spectral resolution of approx 0.01 ppm and normalized limit of detection of approx. 13 nmol s0.5 calculated using the anomeric proton of sucrose at 3 kHz MAS frequency; (2) limited temperature increase inside the MACS insert of only 5 °C at 5 kHz MAS frequency in an 11.74 T magnetic field, rendering MACS suitable to study live biological samples. The wafer-scale fabrication process yields MACS inserts with reproducible properties, readily available to be used on a large scale in bio-chemistry labs. To illustrate the potential of these devices for metabolomic studies, we further report on: (3) ultra-fine 1H-1H and 13C-13C J-couplings resolved within 10 min for a 340 mM uniformly 13C-labeled glucose sample; and (4) single zebrafish embryo measurements through 1H-1H COSY within 4.5 h, opening the gate for the single embryo NMR studies.


Assuntos
Embrião não Mamífero/metabolismo , Glucose/análise , Metabolômica , Ressonância Magnética Nuclear Biomolecular/instrumentação , Peixe-Zebra/embriologia , Animais , Caenorhabditis elegans , Campos Magnéticos , Metabolômica/métodos
14.
Environ Pollut ; 255(Pt 3): 113331, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31614245

RESUMO

We previously found that folic acid (FA) attenuated cardiac defects in zebrafish embryos exposed to extractable organic matter (EOM) from PM2.5, but the underlining mechanisms remain to be elucidated. Since DNA methylation is crucial to cardiac development, we hypothesized that EOM-induced aberrant DNA methylation changes could be diminished by FA supplementation. In this study, zebrafish embryos were exposed to EOM in the absence or presence of FA. Genomic-wide DNA methylation analysis identified both DNA hypo- and hyper-methylation changes in CCGG sites in zebrafish embryos exposed to EOM, which were attenuated by FA supplementation. We identified a total of 316 genes with extensive DNA methylation changes in EOM samples but little or no DNA methylation changes in EOM plus FA samples. The genes were involved in critical cellular processes and signaling pathways important for embryo development. In addition, the EOM-decreased SAM/SAH ratio was counteracted by FA supplementation. Furthermore, FA attenuated the EOM-induced changes in the expression of genes involved in the regulation of DNA methylation and in folate biosynthesis. In conclusion, our data suggest that FA supplementation protected zebrafish embryos from the cardiac developmental toxicity of PM2.5 by alleviating EOM-induced DNA methylation changes.


Assuntos
Ácido Fólico/metabolismo , Material Particulado/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Metilação de DNA/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Coração/efeitos dos fármacos , Material Particulado/metabolismo , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
15.
J Biochem Mol Toxicol ; 33(12): e22408, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31617658

RESUMO

In this study, gene expression alterations of phase I to III enzymes, transcription factors, and microRNA (miRNA) in embryonic zebrafish fibroblasts (ZF4) cells after the treatment of Pb(NO3 )2 and AgNO3 were investigated, to illustrate the possible detoxification pathway of heavy metal ions. It was observed that both metals caused concentration-dependent death and moderate elevation of oxidative stress in ZF4 cells. In response to such toxicity, upregulation of multidrug resistance protein (mdr)4 and multiresistance-associated protein (mrp)1 were found. However, enhanced expression of glutathione S-transferase (gst) and cytochrome P450 (cyp)1a could only be detected during the exposure of Pb2+ . In addition, both metals induced extensive upregulation of pregnane X receptor (pxr), but only moderate elevation of E2-related factor (nrf2), while they suppressed the expression of miR-122 and miR-126. In conclusion, Pb2+ and Ag+ shared the same detoxification mechanism including ABC transporters, Pxr, and miRNA in ZF4 cells, which needs further investigation.


Assuntos
Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Chumbo/toxicidade , Nitratos/toxicidade , Nitrato de Prata/toxicidade , Peixe-Zebra/embriologia , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/metabolismo , Regulação da Expressão Gênica , Glutationa Transferase/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Receptor de Pregnano X/genética , Receptor de Pregnano X/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
16.
Environ Pollut ; 255(Pt 2): 113329, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31600704

RESUMO

Transcription factors including pregnane X receptor (Pxr) and nuclear factor-erythroid 2-related factor-2 (Nrf2) are important modulators of Adenosine triphosphate-binding cassette (ABC) transporters in mammalian cells. However, whether such modulation is conserved in zebrafish embryos remains largely unknown. In this manuscript, pxr- and nrf2-deficient models were constructed with CRISPR/Cas9 system, to evaluate the individual function of Pxr and Nrf2 in the regulation of ABC transporters and detoxification of heavy metal ions like Cd2+ and Ag+. As a result, both Cd2+ and Ag+ conferred extensive interactions with ABC transporters in wild type (WT) embryos: their accumulation and toxicity were affected by the activity of ABC transporters, and they significantly induced the mRNA expressions of ABC transporters. These induction effects were reduced by the mutation of pxr and nrf2, but elevations in the basal expression of ABC transporters compensated for the loss of their inducibility. This could be an explanation for remaining transporter function in both mutant models as well as the unaltered toxicity of metal ions in pxr-deficient embryos. However, mutation of nrf2 disrupted the production of glutathione (GSH), resulting in the enhanced toxicity of Cd2+/Ag+ in zebrafish embryos. In addition, elevated expressions of other transcription factors like aryl hydrocarbon receptor (ahr) 1b, peroxisome proliferator-activated receptor (ppar)-ß, and nrf2 were found in pxr-deficient models without any treatment, while enhanced induction of ahr1b, ppar-ß and pxr could only be seen in nrf2-deficient embryos after the treatment of metal ions, indicating different compensation phenomena for the absence of transcription factors. After all, pxr-deficient and nrf2-deficient zebrafish embryos are useful tools in the functional investigation of Pxr and Nrf2 in the early life stages of aquatic organisms. However, the compensatory mechanisms should be taken into consideration when interpreting the results and need in-depth investigations.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Metais Pesados/toxicidade , Fator 2 Relacionado a NF-E2/genética , Receptor de Pregnano X/genética , Peixe-Zebra/embriologia , Animais , Glutationa/metabolismo , Inativação Metabólica , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Esteroides/genética , Fatores de Transcrição/metabolismo , Proteínas de Peixe-Zebra/metabolismo
17.
Environ Pollut ; 255(Pt 2): 113313, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31600709

RESUMO

Copper oxide nanoparticles (CuO NPs) is one of the most commonly used metal oxide nanoparticles for commercial and industrial products. An increase in the manufacturing and use of the CuO NPs based products has increased the likelihood of their release into the aquatic environment. This has attracted major attention among researchers to explore their impact in human as well as environmental systems. CuO NPs, once released into the environment interact with the biotic and abiotic constituents of the ecosystem. Hence the objective of the study was to provide a holistic understanding of the effect of abiotic factors on the stability and aggregation of CuO NPs and its correlation with their effect on the development of zebrafish embryo. It has been observed that the bioavailability of CuO NPs decrease in presence of humic acid (HA) and heteroagglomeration of CuO NPs occurs with clay minerals. CuO NPs, CuO NPs + HA and CuO NPs + Clay significantly altered the expression of genes involved in development of dorsoventral axis and neural network of zebrafish embryos. However, the presence of HA with clay showed protective effect on zebrafish embryo development. These findings provide new insights into the interaction of NPs with abiotic factors and combined effects of such complexes on developing zebrafish embryos genetic markers.


Assuntos
Argila/química , Cobre/toxicidade , Nanopartículas Metálicas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Bentonita , Cobre/química , Ecossistema , Embrião não Mamífero/anormalidades , Embrião não Mamífero/efeitos dos fármacos , Substâncias Húmicas/análise , Nanopartículas , Óxidos , Poluentes Químicos da Água/análise , Peixe-Zebra/embriologia
18.
Ecotoxicol Environ Saf ; 186: 109754, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31606639

RESUMO

In (eco)toxicology, there is a critical need for efficient methods to evaluate the neurotoxic potential of environmental chemicals. Recent studies proposed analysis of early coiling activity in zebrafish embryos as a powerful tool for the identification of neurotoxic compounds. In order to demonstrate that the analysis of early tail movements of zebrafish embryos allows for the discrimination of neurotoxicants acting via different mechanisms, the present study investigated the effects of four different neurotoxicants on the embryogenesis (fish embryo toxicity test) and early tail coiling movements of zebrafish embryos. Cadmium predominantly increased the frequency of tail coiling at the late pharyngula stage. Dichlorvos delayed embryonic development and caused convulsive tail movements resulting in prolonged duration of tail coils. Embryos exposed to teratogenic concentrations of fluoxetine and citalopram displayed absence of spontaneous tail movements at 24 h post-fertilization. In contrast, a non-teratogenic test concentration of citalopram decreased coiling frequency at multiple time points. Results demonstrated that the analysis of tail coiling movements of zebrafish embryos has the potential to discriminate neurotoxic compounds with different primary modes of action. In addition, chemical-induced effects on coiling activity were shown to potentially overlap with effects on embryogenesis. Further studies are needed to clarify the interplay of unspecific developmental toxicity of neurotoxic chemicals and effects resulting from specific neurotoxic mechanisms.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Movimento/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Testes de Toxicidade/métodos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Cádmio/toxicidade , Citalopram/toxicidade , Diclorvós/toxicidade , Ecotoxicologia/métodos , Desenvolvimento Embrionário , Fluoxetina/toxicidade , Cauda , Peixe-Zebra/embriologia
19.
J Agric Food Chem ; 67(43): 11994-12001, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31618578

RESUMO

Bioactivity-guided isolation of the endophytic fungus Fusarium sambucinum TE-6L residing in Nicotiana tabacum L. led to the discovery of two new angularly prenylated indole alkaloids (PIAs) with pyrano[2,3-g]indole moieties, amoenamide C (1) and sclerotiamide B (2), and four known biosynthetic congeners (3-6). Their structures were determined by comprehensive spectroscopic techniques, electronic circular dichroism (ECD), and X-ray diffraction. Compound 1 containing the bicyclo[2.2.2]diazaoctane core and indoxyl unit is rarely reported. All the compounds were evaluated for their antimicrobial and insecticidal activities. Notably, compounds 1-3 showed potent inhibitory effects against three human- and one plant-pathogenic bacterium, and seven plant-pathogenic fungi. Compounds 2-4 also exhibited remarkable larvicidal activity against first instar larvae of the cotton bollworm Helicoverpa armigera with mortality rates of 70.2%, 83.2%, and 70.5%, respectively. Further toxicity tests on zebrafish embryos were performed to evaluate the potential toxicity of PIAs. Of significance was that compound 3 in particular exhibited the highest activities but the lowest effects on the hatching of embryos among all the compounds. This study provides a basis for understanding developmental toxicity of PIAs exposure to zebrafish embryos, and also indicates the potential environmental risks of other natural compounds exposure in the aquatic ecosystem.


Assuntos
Anti-Infecciosos/química , Endófitos/química , Fusarium/química , Alcaloides Indólicos/química , Inseticidas/química , Animais , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Endófitos/isolamento & purificação , Fungos/efeitos dos fármacos , Fusarium/isolamento & purificação , Alcaloides Indólicos/metabolismo , Alcaloides Indólicos/farmacologia , Inseticidas/metabolismo , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mariposas/efeitos dos fármacos , Tabaco/microbiologia , Peixe-Zebra/embriologia
20.
Environ Pollut ; 255(Pt 2): 113269, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31574395

RESUMO

Triazole fungicides are widely used in agriculture production and have adverse impacts on aquatic organisms. As one of the triazole fungicides, prothioconazole has been reported to cause many toxicological effects, but its risks to aquatic organisms are unknown. In this study, we systematically explored the toxicity effects of prothioconazole exposure on zebrafish embryos (Danio rerio) involving in developmental toxicity, oxidative damage and metabolism disorders. The results showed that prothioconazole exposure to zebrafish embryos produced a series of toxic symptoms, including hatching inhibition, shortening of body length, pericardial cyst and yolk cyst. In addition, prothioconazole exposure caused significant lipid peroxidation and oxidative damage. Particularly, we also found that metabolites and genes involved in lipid metabolism also showed significant changes. This study may provide theoretical basis for systematically assessing the potential risks of zebrafish embryos with prothioconazole exposure.


Assuntos
Embrião não Mamífero/fisiologia , Fungicidas Industriais/toxicidade , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Organismos Aquáticos , Embrião não Mamífero/efeitos dos fármacos , Metabolismo dos Lipídeos , Peroxidação de Lipídeos , Poluentes Químicos da Água/análise , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
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