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1.
Chemosphere ; 235: 1050-1058, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31561294

RESUMO

Lead (Pb) is one of the most toxic heavy metals and has aroused widespread concern as it can cause severe impairments in the developing nervous system. Autophagy has been proposed as an injury factor in Pb-induced neurotoxicity. In this study, we used zebrafish embryo as a model, measured the general toxic effects of Pb, and investigated the effect of Pb exposure on autophagy, and its role in Pb-induced developmental neurotoxicity. Zebrafish embryos were exposed to Pb at concentrations of 0, 0.1, 1 or 10 µM until 4 days post-fertilization. Our data showed that exposure to 10 µM Pb significantly reduced survival rates and impaired locomotor activity. Uptake of Pb was enhanced as the concentration and duration of exposure increased. Inhibition of lysosomal degradation with bafilomycin A1 treatment abolished the suppression of Lc3-II protein expression by Pb. Furthermore, autophagosome formation was inhibited by Pb in the brain. In addition, mRNA expression of beclin1, one of the critical genes in autophagy, were decreased in Pb exposure groups at 72 h post-fertilization. Whole-mount in situ hybridization assay showed that beclin1 gene expression in the brain was reduced by Pb. Rapamycin, an autophagy inducer, partly resolved developmental neurotoxicity induced by Pb exposure. Our results suggest that autophagy plays a protective role in the developmental neurotoxicity of Pb in zebrafish embryos and larvae.


Assuntos
Autofagia/efeitos dos fármacos , Intoxicação do Sistema Nervoso por Chumbo/prevenção & controle , Chumbo/toxicidade , Peixe-Zebra/embriologia , Animais , Expressão Gênica , Larva/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo
2.
Ecotoxicol Environ Saf ; 182: 109449, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31398778

RESUMO

The flame retardant, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), is one of the most developmentally toxic organophosphate flame retardants (OPFRs). However, few mechanistic studies on phenotypic malformation caused by TDCIPP have been conducted. This study investigates the molecular mechanism underlying abnormal tail fin development consistently observed in zebrafish embryos exposed to TDCIPP. The results show that the defects in the tail fin (e.g., bent spine, defective caudal fin, and damaged tip) were associated with altered expression of transcription factors. The significant up-regulation of mmp9 and, among insulin-growth factor (IGF) families, igfbp-1a and igfbp1b was observed, whereas alterations in the expression of cdx4, igf1a, ifg1b, igf2b, and vegaa regulating tail development were dependent on time points. In accordance with changes in mRNA gene expression, TDCIPP impaired vessel formation and disorganized muscle in transgenic Tg(fli-GFP) zebrafish larvae. Furthermore, we found that the overexpression of mmp9 caused by TDCIPP was not linked to igfbp-1. Overall, these findings demonstrate that TDCIPP disrupts the progression of tail fin development, accompanied by defects in vessel and muscle formation in developing zebrafish embryos.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Retardadores de Chama/toxicidade , Compostos Organofosforados/toxicidade , Animais , Animais Geneticamente Modificados , Retardadores de Chama/metabolismo , Larva , Organofosfatos/metabolismo , Fosfatos/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
3.
J Agric Food Chem ; 67(28): 7783-7792, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31267752

RESUMO

The increasing use of pesticides in agriculture and gardening has caused severe deterioration to both the ecosystem and the health of users (human beings), so there is an urgent need for eco- and user-friendly pesticides. Among a variety of herbicides, paraquat (PQ), frequently used as an effective herbicidal agent worldwide, is well-known for its serious toxicity that has killed, and harmed, thousands of people and countless wildlife such as fish. Herein, we present a facile supramolecular formulation of PQ@cucurbit[7]uril (PQ@CB[7]), prepared by simply mixing PQ with equivalent (molar) CB[7] in water. With addition of CB[7], PQ's cellular uptake was dramatically inhibited. The reactive oxygen species (ROS) generation and the associated apoptosis otherwise induced by PQ in cellular models were both reduced, resulting in increased cellular viability. In a wildtype zebrafish model that is a typical fragile wildlife species in the ecosystem, the supramolecular formulation exhibited significantly reduced hepatotoxicity and increased survival rate, in comparison with those of the fish exposed to free PQ. In a mouse model that is clinically relevant to human being, the administration of PQ@CB[7] significantly alleviated major organ injuries and unusual hematological parameters that were otherwise induced by free PQ, resulting in a significantly increased survival rate. Meanwhile, this formulation maintained effective herbicidal activity that was equivalent to that of free PQ. Taken together, this facile supramolecular PQ formulation is providing not only an extremely rare example of an eco- and user-friendly herbicide that has been desired for decades but also a practical solution for green agriculture.


Assuntos
Herbicidas/farmacologia , Paraquat/farmacologia , Animais , Apoptose/efeitos dos fármacos , Química Verde , Herbicidas/síntese química , Herbicidas/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Paraquat/síntese química , Paraquat/química , Poaceae/efeitos dos fármacos , Poaceae/crescimento & desenvolvimento , Peixe-Zebra/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-31255699

RESUMO

Organic anion transporters (OATs) are membrane proteins within the Solute carrier family 22 (SLC22). They play important roles in cellular uptake of various organic compounds, and due to their expression in barrier tissues of major excretory and non-excretory organs are considered as crucial elements in absorption and distribution of a wide range of endobiotic and xenobiotic compounds. Based on our previous work and initial insights on SLC22 members in zebrafish (Danio rerio), in this study we aimed at in vitro characterization of Oat1 and Oat3 transporters and understanding of their interaction with potential physiological substrates. We first performed synteny analysis to describe in more detail orthological relationship of zebrafish oat1 and oat3 genes. We then developed stable cell lines overexpressing Oat1 and Oat3, and identified Lucifer yellow as Oat1 model fluorescent substrate (Km = 11.4 µM) and 6-carboxyfluorescein as Oat3 model substrate (Km = 5.8 µM). Initial identification performed using the developed assays revealed Kreb's cycle intermediates, bilirubin, bile salts and steroid hormones as the most potent of Oat1 and Oat3 interactors, with IC50 values in micromolar range. Finally, we showed that bilirubin, deoxycholic acid, α-ketoglutarate, pregnenolone, estrone-3-sulfate and corticosterone are in vitro substrates of zebrafish Oat1, and bilirubin and deoxycholic acid are Oat3 substrates. In conclusion, using the approach described, structural and functional similarities of both transporters to human and mammalian orthologs are revealed, their broad ligand selectivity confirmed, potent interactors among endobiotic compounds identified, and first indications of their potential physiological role(s) in zebrafish obtained.


Assuntos
Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Avaliação Pré-Clínica de Medicamentos , Proteína 1 Transportadora de Ânions Orgânicos/antagonistas & inibidores , Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores , Ligação Proteica , Transporte Proteico , Proteínas de Peixe-Zebra/antagonistas & inibidores
5.
Toxicol Lett ; 314: 43-52, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31310794

RESUMO

Thioredoxin is an evolutionarily conserved antioxidant protein that plays a crucial role for fundamental cellular processes and embryonic development. Growing evidence support that Thioredoxin influences cellular response to chemicals insults, particularly those accompanying oxidative stress. The mechanisms underlying the functions of Thioredoxin1 in the embryonic development under the environmental toxicant exposure remain, however, largely unexplored. We report here that thioredoxin1 becomes differentially expressed in zebrafish embryos after exposure to 9 out of 11 environmental chemicals. In situ gene expression analysis show that thioredoxin1 is expressed in neurons, olfactory epithelia, liver and swim bladder under normal conditions. After MeHg exposure, however, thioredoxin1 is ectopically induced in the hair cells of the lateral line and in epithelia cells of the pharynx. Knockdown of Thioredoxin1 induces hydrocephalus and increases cell apoptosis in the brain ventricular epithelia cells. In comparison with 5% malformation in embryos injected with control morpholino, MeHg induces more than 77% defects in Thioredoxin1 knockdown embryos. Our data suggest that there is an association between hydrocephalus and Thioredoxin1 malfunction in embryonic development, and provide valuable information to elucidate the protective role of Thioredoxin1 against chemicals disruption.


Assuntos
Encéfalo/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Hidrocefalia/induzido quimicamente , Tiorredoxinas/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Animais Geneticamente Modificados , Apoptose/efeitos dos fármacos , Encéfalo/embriologia , Encéfalo/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Embrião não Mamífero/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica no Desenvolvimento , Hidrocefalia/embriologia , Hidrocefalia/genética , Hidrocefalia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Tiorredoxinas/genética , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
6.
Ecotoxicol Environ Saf ; 182: 109442, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31352214

RESUMO

To identify the physical effects, behavioral changes, and gene expression profiles of the phase 1 detoxification-related gene (cyp 1a) and oogenesis-related gene (vtg 1) induced by microplastics, high-density polyethylene microplastics of various sizes were used because of their dominance in coastal areas and effluent samples in Hong Kong. Adult zebrafish were used as the model organism to identify the upper and lower boundaries of microplastics ingestion and were exposed to individual polyethylene microplastics in five size ranges (10-22 µm, 45-53 µm, 90-106 µm, 212-250 µm, and 500-600 µm) at a concentration of 2 mg/L for 96 h. To study behavioral changes and targeted gene expression profiles via real-time PCR (qPCR), a mixture of microplastics in three size ranges at effluent-related (11 particles/L), moderate (110 particles/L), and high concentrations (1,100 particles/L) were applied for 96 h. The zebrafish behavior was recorded by a video camera and by two observers (interrater reliability, >85%). The results implied that the upper and lower size boundaries for microplastic ingestion were 558.4 ±â€¯26.2 µm (yellow) and 19.7 ±â€¯3.1 µm (red), respectively. In addition, 61 ±â€¯10% of fish in medium concentration treatments and 61 ±â€¯10% of fish in high concentration treatments were found with the microplastic ingestion and remaining in their intestine. In addition, 28 ±â€¯10% of fish in high concentration treatments were found with microplastic retaining in their gills (No. of fishes = 18 in each treatment). The presence of microplastics, which occupied 89 ±â€¯6% of intestine area, reduced the voids inside the intestine for feed. The expression of cyp1a in the intestine (medium concentration) and vtg1 in the liver (medium and high concentration) showed significant up-regulation, and abnormal behavior (i.e., seizures and tail bent downward) was observed (medium and high concentration). In summary, the effects on the aryl hydrocarbon receptor (AHR) pathway, disruption of the oogenesis process, and neurotoxicity could be caused by acute exposure of adult zebrafish to microplastics.


Assuntos
Plásticos/toxicidade , Polietileno/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Brânquias/efeitos dos fármacos , Hong Kong , Reprodutibilidade dos Testes , Testes de Toxicidade Aguda , Peixe-Zebra/metabolismo
7.
Ecotoxicol Environ Saf ; 182: 109380, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31279279

RESUMO

Ultraviolet (UV) is an omnipresent environmental carcinogen transmitted by sunlight. Excessive UV irradiation has been correlated to an increased risk of skin cancers. UVB, the most mutagenic component among the three UV constituents, causes damage mainly through inducing DNA damage and oxidative stress. Therefore, strategies or nutrients that strengthen an individual's resistance to UV-inflicted harmful effects shall be beneficial. Folate is a water-soluble B vitamin essential for nucleotides biosynthesis, and also a strong biological antioxidant, hence a micronutrient with potential of modulating individual's vulnerability to UV exposure. In this study, we investigated the impact of folate status on UV sensitivity and the protective activity of folate supplementation using a zebrafish model. Elevated reactive oxygen species (ROS) level and morphological injury were observed in the larvae exposed to UVB, which were readily rescued by supplementing with folic acid, 5-formyltetrahydrofolate (5-CHO-THF) and N-acetyl-L-cysteine (NAC). The UVB-inflicted abnormalities and mortality were worsened in Tg(hsp:EGFP-γGH) larvae displaying folate deficiency. Intriguingly, only supplementation with 5-CHO-THF, as opposed to folic acid, offered significant and consistent protection against UVB-inflicted oxidative damage in the folate-deficient larvae. We concluded that the intrinsic folate status correlates with the vulnerability to UVB-induced damage in zebrafish larvae. In addition, 5-CHO-THF surpassed both folic acid and NAC in preventing UVB-inflicted oxidative stress and injury in our current experimental zebrafish model.


Assuntos
Deficiência de Ácido Fólico/prevenção & controle , Leucovorina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Complexo Vitamínico B/farmacologia , Peixe-Zebra/metabolismo , Acetilcisteína/farmacologia , Animais , Antioxidantes/farmacologia , Suplementos Nutricionais , Deficiência de Ácido Fólico/metabolismo , Larva/efeitos dos fármacos , Larva/metabolismo , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo
8.
Ecotoxicol Environ Saf ; 182: 109406, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31288122

RESUMO

Obesity, a risk factor for the development of type-2 diabetes, hypertension, cardiovascular disease, hepatic steatosis and some cancers, has been ranked in the top 10 health risk in the world by the World Health Organization. Despite the growing body of literature evidencing an association between the obesity epidemic and specific chemical exposure across a wide range of animal taxa, very few studies assessed the effects of chemical mixtures and environmental samples on lipid homeostasis. Additionally, the mode of action of several chemicals reported to alter lipid homeostasis is still poorly understood. Aiming to fill some of these gaps, we combined an in vivo assay with the model species zebrafish (Danio rerio) to screen lipid accumulation and evaluate expression changes of key genes involved in lipid homeostasis, alongside with an in vitro transactivation assay using human and zebrafish nuclear receptors, retinoid X receptor α and peroxisome proliferator-activated receptor γ. Zebrafish larvae were exposed from 4 th day post-fertilization until the end of the experiment (day 18), to six different treatments: experimental control, solvent control, tributyltin at 100 ng/L Sn and 200 ng/L Sn (positive control), and wastewater treatment plant influent at 1.25% and 2.5%. Exposure to tributyltin and to 2.5% influent led to a significant accumulation of lipids, with white adipose tissue deposits concentrating in the perivisceral area. The highest in vitro tested influent concentration (10%) was able to significantly transactivate the human heterodimer PPARγ/RXRα, thus suggesting the presence in the influent of HsPPARγ/RXRα agonists. Our results demonstrate, for the first time, the ability of complex environmental samples from a municipal waste water treatment plant influent to induce lipid accumulation in zebrafish larvae.


Assuntos
Larva/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/induzido quimicamente , Compostos de Trialquitina/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Relação Dose-Resposta a Droga , Homeostase , Humanos , Larva/metabolismo , Obesidade/metabolismo , Águas Residuárias/química , Purificação da Água
9.
Chemosphere ; 233: 579-589, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31195263

RESUMO

Complex interactions have been established between nanoparticles (NPs) and heavy metals in real environments. Herein we used zebrafish embryos to investigate the influence of titanium dioxide NPs (n-TiO2) on the uptake, bioconcentration, and depuration, and toxicity of Pb. The formation of n-TiO2-Pb complexes was confirmed in an exposure suspension. An increase in Pb bioconcentration was observed in zebrafish embryos upon co-exposure to n-TiO2 and Pb; moreover, n-TiO2-Pb complexes could be found in the embryos, indicating the bioavailability of NPs. However, there was no difference in the depuration rates of Pb in the presence of n-TiO2. Metallothionein (MT) content was significantly increased upon exposure to Pb alone, and the content significantly increased even further upon co-exposure. A downregulation in the expression levels of the neurodevelopment-related genes gfap, syn2α, and elavl3 was observed in the embryos, and we also noted a reduction in the swimming speed of and the total distance traveled by the larvae. To summarize, our results indicate that n-TiO2 can act as an effective carrier of Pb to enhance its uptake, bioavailability, and toxicity in zebrafish embryos.


Assuntos
Embrião não Mamífero/fisiologia , Chumbo/toxicidade , Nanopartículas Metálicas/toxicidade , Titânio/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Disponibilidade Biológica , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Larva/metabolismo , Metalotioneína/metabolismo , Nanopartículas/toxicidade , Peixe-Zebra/metabolismo
10.
Environ Pollut ; 249: 1049-1059, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31146311

RESUMO

Tebuconazole is a widely used fungicide that has been detected in water ecosystems, of which the concentrations may affect the endocrine function of aquatic organisms. At present study, tissue-specific bioaccumulation of tebuconazole was found in ovary of adult zebrafish, indicating a potential risk of endocrine disruption. In order to evaluate the potential endocrine disrupting effects, three life stages (2 hpf (hours post-fertilization) -60 dpf (days post-fertilization), Stage I; 60-120 dpf, Stage II; 180-208 dpf, Stage III) of zebrafish (Danio rerio) were chronically exposed to tebuconazole at the concentrations ranging from 0.05 mg/L to 1.84 mg/L. Result showed that exposed to tebuconazole could lead to a male-biased sex differentiation in juvenile zebrafish and significant decrease of the percentage of germ cells in sexually-mature zebrafish. Egg production was significantly inhibited by 57.8% and 19.2% after Stage II- and Stage III-exposures, respectively. The contents of 17ß-estradiol in gonad decreased by 63.5% when exposed to 0.20 mg/L tebuconazole at Stage II and by 49.5% after exposed to 0.18 mg/L tebuconazole at Stage III, respectively. For all stages exposure, reductions in 17ß-estradiol/testosterone ratio were observed, indicating an imbalance in steroids synthesis. Additionally, tebuconazole reduced the expression of cyp19a, which was consistent with the decrease of E2 level. In overall, the present findings indicated that, playing as an anti-estrogen-like chemical, tebuconazole inhibited the expression of Cyp19, thereby impairing steroid hormones biosynthesis, leading to a diminished fecundity of zebrafish.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Fungicidas Industriais/toxicidade , Gônadas/efeitos dos fármacos , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/crescimento & desenvolvimento , Animais , Aromatase/metabolismo , Embrião não Mamífero/metabolismo , Disruptores Endócrinos/metabolismo , Feminino , Fungicidas Industriais/metabolismo , Gônadas/embriologia , Diferenciação Sexual/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Triazóis/metabolismo , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/metabolismo
11.
Bull Environ Contam Toxicol ; 103(2): 267-273, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172221

RESUMO

The development of nanotechnology has drawn increased attention to the risks of nanoparticles (NPs). In this work, the near-infrared persistent luminescence imaging technique was used to track the biodistribution of NPs in vivo in zebrafish. Zebrafish were used as a vertebrate animal model to show NPs distribution and the effects of exposure. ZnGa2O4:Cr (ZGOC) was chosen as the probe in this work. In continuous exposure experiments, the results showed more particles accumulated in the intestines than in the gills in both groups. In both the gills and abdomen, the NPs contents were greater in the ZGOC-NH2-treated groups than in the ZGOC groups, and the NPs caused damage to the gills and intestines. Removal exposure experiments indicated that ZGOC and ZGOC-NH2 could be excreted from the body. The metabolism, excretion of NPs, the quantification and monitoring of NPs behavior in biological systems should be examined in further studies.


Assuntos
Nanopartículas/metabolismo , Poluentes Químicos da Água/farmacocinética , Peixe-Zebra/metabolismo , Animais , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Medições Luminescentes , Nanopartículas/química , Nanopartículas/toxicidade , Imagem Óptica , Propriedades de Superfície , Distribuição Tecidual , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade
12.
Ecotoxicol Environ Saf ; 181: 559-571, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31238190

RESUMO

Warfarin is the most worldwide used anticoagulant drug and rodenticide. Since it crosses placental barrier it can induce warfarin embryopathy (WE), a fetal mortality in neonates characterized by skeletal deformities in addition to brain hemorrhages. Although the effects of warfarin exposure in aquatic off target species were already described, the particular molecular toxicological mechanisms during early development are still unclear. Here, we used zebrafish (Danio rerio) to describe and compare the developmental effects of warfarin exposure (0, 15.13, 75.68 and 378.43 mM) on two distinct early developmental phases (embryos and eleuthero-embryos). Although exposure to both developmental phases induced fish mortality, only embryos exposed to the highest warfarin level exhibited features mimicking mammalian WE, e.g. high mortality, higher incidence of hemorrhages and altered skeletal development, among other effects. To gain insights into the toxic mechanisms underlying warfarin exposure, the transcriptome of embryos exposed to warfarin was explored through RNA-Seq and compared to that of control embryos. 766 differentially expressed (564 up- and 202 down-regulated) genes were identified. Gene Ontology analysis revealed particular cellular components (cytoplasm, extracellular matrix, lysosome and vacuole), biological processes (mainly amino acid and lipid metabolism and response to stimulus) and pathways (oxidative stress response and apoptosis signaling pathways) being significantly overrepresented in zebrafish embryos upon warfarin exposure. Protein-protein interaction further evidenced an altered redox system, blood coagulation and vasculogenesis, visual phototransduction and collagen formation upon warfarin exposure. The present study not only describes for the first time the WE in zebrafish, it provides new insights for a better risk assessment, and highlights the need for programming the rat eradication actions outside the fish spawning season to avoid an impact on off target fish community. The urge for the development of more species-specific anticoagulants for rodent pest control is also highlighted.


Assuntos
Anormalidades Induzidas por Medicamentos/metabolismo , Anticoagulantes/toxicidade , Osso Nasal/anormalidades , Rodenticidas/toxicidade , Varfarina/efeitos adversos , Varfarina/toxicidade , Poluentes Químicos da Água/toxicidade , Anormalidades Induzidas por Medicamentos/genética , Animais , Modelos Animais de Doenças , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Humanos , Osso Nasal/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transcriptoma , Varfarina/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
13.
Chemosphere ; 232: 171-179, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31154177

RESUMO

Tricyclazole is widely used in agriculture as a pesticide, but its toxicity in vertebrates is currently poorly evaluated. In this study, we used zebrafish to assess the toxicity of tricyclazole. We found that tricyclazole induces liver damage, or hepatotoxicity, in zebrafish, during both development and adulthood. In embryos, we found that tricyclazole affected the liver development rather than other endodermal tissues such as gut and pancreas. In both embryos and adult zebrafish livers, tricyclazole disrupted the relationship between oxidant and antioxidant system and resulted in reactive oxygen species (ROS) overload. Meanwhile, it triggered hepatocyte apoptosis and disturbed carbohydrate/lipid metabolism and energy demand systems. These results suggested that tricyclazole could cause severe consequences for vertebrate hepatic development and function.


Assuntos
Tiazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose , Doença Hepática Induzida por Substâncias e Drogas , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra/metabolismo
14.
Environ Pollut ; 252(Pt B): 1059-1067, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31252103

RESUMO

Climate change and pharmaceuticals contamination constitute two of the most relevant stressors on the aquatic ecosystems, however, there is a huge lack of information regarding the interactive effects of both stressors. For that, a mesocosm experiment was implemented where adult zebrafish were exposed to combined temperature and the progestin levonorgestrel (LNG) for 21 days. Considering that the liver is one of the organs where there is a greater metabolization and accumulation of toxicants, the main objective of this work was to assess the effects of both stressors on the female zebrafish hepatocytes morphology and functioning, through stereological and immunohistochemical techniques. Our results revealed an increase of coefficient of variation of the number distribution of hepatocytes volume (CVN(υ)) for individuals exposed to LNG, which denotes an increase of the hepatocytes size variability and is suggestive of functional impacts. This was corroborated by the signs of increased glycogen content with the exposure to increased LNG concentrations and temperature, indicating modified hepatocyte glycogen metabolism. Such disturbances can be considered indicators that the fish had to deal with impacts caused by the stress factors. Regarding the immunoreactivity, from the four proteins selected (catalase, CYP1A, HSP90 and Vtg), just in two of them (catalase and Vtg) were observed some responses to both stressors. For catalase there was a hormetic response, in which exposure to lower LNG concentrations caused a significant higher positive immunostaining than under higher LNG concentrations. While, for Vtg, significant effects of temperature and LNG existed, in which a decline in Vtg immunostaining was observed with exposure to higher temperature and lower LNG concentrations. These results should be seen as a warning sign about fine impacts of multiple stressors, such as temperature and progestogens, on the structure and functioning of zebrafish liver and potentially in other aquatic organisms, and on their health implications.


Assuntos
Levanogestrel/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Temperatura Ambiente , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Catalase/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Feminino , Proteínas de Choque Térmico HSP90/metabolismo , Imuno-Histoquímica , Vitelogeninas/metabolismo
15.
Ecotoxicol Environ Saf ; 182: 109377, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31254858

RESUMO

The measurement of oxygen consumption rate (OCR) provides a comprehensive understanding of mitochondrial metabolism. However, no study has been conducted to investigate the mitochondrial dysfunction caused by organophosphate flame retardants (OPFRs). The objectives of this study were to optimize the experimental conditions to measure OCR in zebrafish embryos using the Seahorse XFe 24 Extracellular Flux Analyzer, and to investigate the changes of OCR in zebrafish embryos exposed to OPFRs. We first optimized the experimental conditions such as the number of embryos, concentrations of inhibitors, and time points. We determined the factors, i.e., three embryos, 12.5 µM of oligomycin, 8 µM of carbonyl cyanaide 4-(trifluoromethoxy) phenylhydrazone (FCCP), and 24 hpf (hours post-fertilization) time point, for obtaining the typical pattern of OCR in dechorinated zebrafish embryos. After confirming the determinants upon exposure of triclosan, the inhibition of OCR was measured in zebrafish embryos exposed to two major OPFRs, triphenyl phosphate (TPHP) and tris (1,3-dichloro-2-propyl) phosphate (TDCIPP). We found that significant inhibition of OCR was observed in basal respiration for TPHP, and in basal and maximal respiration for TDCIPP exposure, respectively. We suggest the optimum conditions of the Seahorse XFe 24 analyzer to better evaluate OCR in zebrafish embryos, and demonstrate the potential of TPHP and TDCIPP to cause the disruption of energy metabolism associated with mitochondrial dysfunction.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Retardadores de Chama/toxicidade , Organofosfatos/toxicidade , Consumo de Oxigênio/efeitos dos fármacos , Peixe-Zebra/metabolismo , Animais , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Modelos Teóricos
16.
Aquat Toxicol ; 213: 105219, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31195325

RESUMO

Nrf2 is a crucial transcription factor that regulates the expression of cytoprotective enzymes and controls cellular redox homeostasis. Both arsenic and fluoride are potent toxicants that are known to induce Nrf2. They are reported to coexist in many areas of the world leading to complex mixture effects in exposed organisms. The present study investigated the expression of Nrf2 and related xenobiotic metabolizing enzymes along with other stress markers such as histopathological alterations, catalase activity, reduced glutathione content and lipid peroxidation in zebrafish liver as a function of combined exposure to environmentally relevant concentrations of arsenic (37.87 µgL-1 or 5.05 × 10-7 M) and fluoride (6.8 mg L-1 or 3.57 × 10-4 M) for 60 days. The decrease in the total reduced glutathione level was evident in all treatment conditions. Hyperactivity of catalase along with conspicuous elevation in reactive oxygen species, malondialdehyde content and histo-architectural anomalies signified the presence of oxidative stress in the treatment groups. Nrf2 was seen to be induced at both transcriptional and translational levels in case of both individual and co-exposure. The same pattern was observed in case of its nuclear translocation also. From the results of qRT-PCR it was evident that at each time point co-exposure to arsenic and fluoride seemed to alter the gene expression of Cu/Zn Sod, Mn Sod, Gpx and Nqo1 just like their individual exposure but at a very low magnitude. In conclusion, this study demonstrates for the first time the differential expression and activity of Nrf2 and other stress response genes in the zebrafish liver following individual and combined exposure to arsenic and fluoride.


Assuntos
Arsênico/toxicidade , Fluoretos/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Fator 2 Relacionado a NF-E2/genética , Xenobióticos/metabolismo , Peixe-Zebra/metabolismo , Animais , Catalase/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
17.
Chemosphere ; 229: 169-180, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31078031

RESUMO

Although silver nanoparticles (AgNPs) are used in various commercial products, the biological effects of AgNPs on fish embryogenesis and the underlying molecular mechanisms are still poorly understood. In this study, both touch responses and neuron membrane potential were found to be abnormal in AgNPs-stressed embryos. Moreover, neurogenesis genes were unveiled to be down-regulated and were enriched in ligand-gated ion channel activity, dopamine receptor signaling pathway, etc. in AgNPs-stressed embryos by microarray assays. Additionally, the down-regulated expression of otpa/sncgb - gad1b/gad2 dopaminergic neurotransmitter genes, robo2 - vim and glrbb synaptic transmission genes, and motor neuron genes isl1 &isl2a was further identified in both AgNPs- and Ag+-stressed embryos by qPCR, whole-mount in situ hybridization (WISH), and by using specific promoter-derived GFP fluorescence transgenic zebrafish. Moreover, the reduced expression of gad1b, gad2, and isl1 could be recovered by adding Ag+ chelating compound l-cysteine in AgNPs stressed embryos. Our results reveal for the first time that it is through damaging the formation of neural circuits, including dopaminergic neurotransmitter, synaptic transmission, and motor activities, that AgNPs induce abnormal electrical membrane properties, leading to dysfunctional touch responses and locomotor escape responses mostly via their released Ag+ during embryogenesis.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Fenômenos Fisiológicos do Sistema Nervoso/efeitos dos fármacos , Prata/química , Prata/toxicidade , Tato/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Embrião não Mamífero/fisiologia , Tato/fisiologia , Peixe-Zebra/metabolismo , Peixe-Zebra/fisiologia , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
18.
Sci Total Environ ; 682: 128-137, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31117014

RESUMO

As emerging contaminants, microplastics (MPs) are predicted to act as vectors for other contaminants and their combined effects are largely unknown. In this study, the combined effects of MPs and natural organic matter (NOM) on the accumulation and toxicity of copper (Cu) in zebrafish (Danio rerio) were investigated. As a result, small-size MPs could absorb more Cu than large-size MPs. The presence of NOM promoted Cu adsorption on MPs in the pH range of 6-8. Our results demonstrate that the combination of MPs and NOM increased Cu accumulation in the livers and guts in a size-depended manner. Correspondingly, the results of biochemical test showed that MPs and NOM could aggravate Cu-toxicity in the livers and guts, which is manifested in the increased levels of malonaldehyde (MDA) and metallothionein (MT) and decreased levels of superoxide dismutase (SOD). Furthermore, the results of transcriptomic analysis suggested that such aggravation of toxicity was mainly attributed to the inhibition of Cu-ion transport and the enhanced oxidative stress. Since the co-existence of MPs and NOM in the environment is inevitable, their enhancement effects on the bioaccumulation and toxicity of other pollutants such as heavy metals deserve more attention.


Assuntos
Cobre/toxicidade , Substâncias Húmicas/toxicidade , Poliestirenos/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Distribuição Aleatória
19.
Ecotoxicol Environ Saf ; 180: 269-279, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31100591

RESUMO

With the broad application of nanoparticles, nanotoxicology has attracted substantial attention in environmental science. However, the methods for detecting few and targeted genes or proteins, even single omics approaches, may miss other responses, including the major responses induced by nanoparticles. To determine the actual toxicological mechanisms of zebrafish brains induced by graphene oxide (GO, a popular carbon-based nanomaterial applied in various fields) at nonlethal concentrations, multi-omics and regular analyses were combined. The biomolecule responses were remarkable, although GO was not obviously observed in brain tissues. The trends for gene and protein changes were the same and accounted for 3.53% and 5.36% of all changes in the genome and proteome, respectively, suggesting a limitation of single omics analysis. Transcriptomics and proteomics analyses indicated that GO affected the functions or pathways of the troponin complex, actin cytoskeleton, monosaccharide transmembrane transporter activity, oxidoreductase activity and focal adhesion. Both metabolomics and proteomics revealed mitochondrial dysfunction and disruption of the citric acid cycle. The integrated analysis of omics, transmission electron microscopy and immunostaining confirmed that GO induced energy disruptions and mitochondrial damage by downregulating tubulin. The combination of multi-omics and regular analyses provides insights into the actual and highly influential mechanisms underlying nanotoxicity.


Assuntos
Encéfalo/efeitos dos fármacos , Grafite/toxicidade , Nanopartículas/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Encéfalo/metabolismo , Citoesqueleto/metabolismo , Relação Dose-Resposta a Droga , Metabolismo Energético/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Metabolômica/métodos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteômica/métodos , Peixe-Zebra/genética
20.
Ecotoxicol Environ Saf ; 180: 326-332, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31100596

RESUMO

Aniline and aniline derivatives have been widely used in the production of pesticides, pharmaceuticals, cosmetic, dyes, rubber, and adhesives products. These chemicals can easily be released into the environment through industrial and municipal discharges or as degradation byproducts. Several studies have suggested that aniline and some of its derivatives could cause reproductive toxicity in aquatic organisms. However, knowledge on the endocrine disruption potentials of these chemicals is limited only to aniline and associated mechanisms are rarely investigated. The objective of this study was to investigate the potential of major aniline derivatives, i.e., 3,4-dichloroaniline (3,4-DCA), 1-naphthylamine (1-NPA), and 4,4'-methylenedianiline (4,4'-MDA), to disrupt sex steroid production and other biological processes. For this purpose, the human adrenal H295R cell line and adult male zebrafish (Danio rerio) were used. In the H295R cell line, all tested aniline derivatives decreased testosterone (T) levels. Regulatory changes of several steroidogenic genes, i.e., down-regulation of StAR or CYP17 genes, and up-regulation of CYP19A, observed in the H295R cells could explain the sex hormone disruption. In male zebrafish, generally similar directions of changes, i.e., decreases in T levels and increased E2/T ratios, were observed. Again, down-regulation of key steroidogenic genes such as cyp17 or 3ß-hsd, but slight up-regulation of cyp19a gene observed in the fish could explain the sex hormone changes. The results of our study demonstrate that all tested aniline derivatives could influence steroidogenesis and disrupt sex hormone balance toward reduced androgenicity. Consequences of anti-androgenicity following long-term exposure warrant further investigation.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Compostos de Anilina/toxicidade , Disruptores Endócrinos/toxicidade , Testosterona/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Glândulas Suprarrenais/metabolismo , Animais , Aromatase/genética , Linhagem Celular , Família 17 do Citocromo P450/genética , Relação Dose-Resposta a Droga , Humanos , Masculino , Fosfoproteínas/genética
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