Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.524
Filtrar
1.
Ecotoxicol Environ Saf ; 203: 110994, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888603

RESUMO

The effects of cyanobacteria (Aphanizomenon flos-aquae (90%), Microcystis aeruginosa) and dense Elodea canadensis beds on the health endpoints of the amphipod Gmelinoides fasciatus and bivalve mollusc Unio pictorum were examined in mesocosms with simulated summer conditions (July-August 2018) in the environment of the Rybinsk Reservoir (Volga River Basin, Russia). Four treatments were conducted, including one control and three treatments with influencing factors, cyanobacteria and dense elodea beds (separately and combined). After 20 days of exposure, we evaluated the frequency of malformed and dead embryos in amphipods, heart rate (HR) and its recovery (HRR) after stress tests in molluscs as well as heat tolerance (critical thermal maximum or CTMax) in both amphipods and molluscs. The significant effect, such as elevated number of malformed embryos, was recorded after exposure with cyanobacteria (separately and combined with elodea) and presence of microcystins (MC) in water (0.17 µg/l, 40% of the most toxic MC-LR contribution). This study provided evidence that an elevated number (>5% of the total number per female) of malformed embryos in amphipods showed noticeable toxicity effects in the presence of cyanobacteria. The decreased oxygen under the influence of dense elodea beds led to a decrease in HR (and an increase in HRR) in molluscs. The notable effects on all studied biomarkers, embryo malformation frequency and heat tolerance in the amphipod G. fasciatus, as well as the heat tolerance and heart rate in the mollusc U. pictorum, were found when both factors (elodea and cyanobacteria) were combined. The applied endpoints could be further developed for environmental monitoring, but the obtained results support the importance of the combined use of several biomarkers and species, especially in the case of multi-factor environmental stress.


Assuntos
Anfípodes/efeitos dos fármacos , Bivalves/efeitos dos fármacos , Cianobactérias/metabolismo , Monitoramento Ambiental/métodos , Hydrocharitaceae/metabolismo , Poluentes Químicos da Água/toxicidade , Anfípodes/metabolismo , Animais , Aphanizomenon/metabolismo , Biomarcadores/análise , Bivalves/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Microcistinas/metabolismo , Microcistinas/toxicidade , Microcystis/metabolismo , Federação Russa , Poluentes Químicos da Água/metabolismo
2.
Ecotoxicol Environ Saf ; 203: 111043, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888597

RESUMO

Intraspecific difference in toxicity brings uncertainty to ecological risk assessment (ERA) and water quality criteria (WQC) of chemicals. Here, we compared intraspecies sensitivity to toxicants for Mesocyclops leuckarti of which toxicity data was obtained from published literatures, and zebrafish Danio rerio of which toxicity data was done in this study). Due to the internal concentration of chemicals not measured, simplified toxicokinetic-toxicodynamic (TK-TD) models were used, and we investigated whether TK-TD parameters estimated by Bayesian method might represent the differences in sensitivity between life-stages of 2 species. The results demonstrated that the difference in TK-TD parameters (background mortality m0, no effect concentration NEC, the killing rate ks, and the dominant rate kd) could represent the toxicity difference between life-stages of individual species. The TK-TD model could predict toxicity in individual species (Cyprinus carpio L., Enchytraeus crypticus, Folsomia candida, Hyalella Azteca) exposed to different chemical concentrations and successfully extrapolate toxicity between different life stages of Mesocyclops leuckarti and Danio rerio by scaling several TK-TD parameters. The modified TK-TD model on the extrapolation toxicity of chemicals between life stages for species could be useful for the ERA and for deriving and revising WQC for chemicals.


Assuntos
Carpas/metabolismo , Copépodes/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Larva/efeitos dos fármacos , Modelos Biológicos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Teorema de Bayes , Bioacumulação , Carpas/crescimento & desenvolvimento , Copépodes/crescimento & desenvolvimento , Embrião não Mamífero/metabolismo , Larva/metabolismo , Medição de Risco , Especificidade da Espécie , Toxicocinética , Peixe-Zebra/crescimento & desenvolvimento
3.
Chemosphere ; 258: 127385, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947675

RESUMO

2,2,4,4-tetrabromodiphenyl ether (BDE-47) has received considerable attention because of its high detection level in biological samples and potential developmental toxicity. Here, using zebrafish (Danio rerio) as the experimental animal, we investigated developmental effects of BDE-47 and explored the potential mechanism. Zebrafish embryos at 4 h post-fertilization (hpf) were exposed to 0.312, 0.625 and 1.25 mg/L BDE-47 to 74-120 hpf. We found that BDE-47 instigated a dose-related developmental toxicity, evidenced by reduced embryonic survival and hatching rate, shortened body length and increased aberration rate. Meanwhile, higher doses of BDE-47 reduced mitochondrial membrane potential and ATP production but increased apoptosis in zebrafish embryos. Expression of genes involved in mitochondrial oxidative phosphorylation (OXPHOS) (ndufb8, sdha, uqcrc1, cox5ab and atp5fal) were negatively related to BDE-47 doses in zebrafish embryos. Moreover, exposure to BDE-47 at 0.625 or 1.25 mg/L impaired mitochondrial biogenesis and mitochondrial dynamics. Our data further showed that BDE- 47 exposure induced excessive reactive oxygen species (ROS) and oxidative stress, which was accompanied by the activation of c-Jun N-terminal Kinase (JNK). Antioxidant NAC and JNK inhibition could mitigate apoptosis in embryos and improve embryonic development in BDE-47-treated zebrafish, suggesting the involvement of ROS/JNK pathway in embryonic developmental changes induced by BDE-47. Altogether, our data suggest here that developmental toxicity of BDE-47 may be associated with mitochondrial ROS-mediated JNK signaling in zebrafish embryo.


Assuntos
Éteres Difenil Halogenados/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra/metabolismo
4.
Chemosphere ; 254: 126792, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32957266

RESUMO

Iron oxide nanoparticles (IONPs) are used in several medical and environmental applications, but their mechanism of action and hazardous effects to early developmental stages of fish remain unknown. Thus, the present study aimed to assess the developmental toxicity of citrate-functionalized IONPs (γ-Fe2O3 NPs), in comparison with its dissolved counterpart, in zebrafish (Danio rerio) after static and semi-static exposure. Embryos were exposed to environmental concentrations of both iron forms (0.3, 0.6, 1.25, 2.5, 5 and 10 mg L-1) during 144 h, jointly with negative control group. The interaction and distribution of both Fe forms on the external chorion and larvae surface were measured, following by multiple biomarker assessment (mortality, hatching rate, neurotoxicity, cardiotoxicity, morphological alterations and 12 morphometrics parameters). Results showed that IONPs were mainly accumulated on the zebrafish chorion, and in the digestive system and liver of the larvae. Although the IONPs induced low embryotoxicity compared to iron ions in both exposure conditions, these nanomaterials induced sublethal effects, mainly cardiotoxic effects (reduced heartbeat, blood accumulation in the heart and pericardial edema). The semi-static exposure to both iron forms induced high embryotoxicity compared to static exposure, indicating that the nanotoxicity to early developmental stages of fish depends on the exposure system. This is the first study concerning the role of the exposure condition on the developmental toxicity of IONPs on fish species.


Assuntos
Compostos Férricos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Cloretos , Embrião não Mamífero/efeitos dos fármacos , Ferro/farmacologia , Larva/efeitos dos fármacos , Nanopartículas/toxicidade , Peixe-Zebra/embriologia
5.
Bull Environ Contam Toxicol ; 105(4): 530-537, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32940716

RESUMO

An increase in the production and usage of gold nanoparticles (AuNPs) triggers the necessity to focus on their impact on ecosystems. Therefore, the purpose of this study was to investigate the acute toxicity of AuNPs and ionic gold (Au (III)) to organisms representing all trophic levels of the aquatic ecosystem, namely producers (duckweed Lemna minor), consumers (crustacean Daphnia magna, embryos of Danio rerio) and decomposers (bacteria Vibrio fischeri). The organisms were exposed according to a standardized protocol for each species and endpoints. The AuNPs (1.16 and 11.6 d.nm) were synthesized using citrate (CIT) and polyvinylpyrrolidone (PVP) as capping agents, respectively. It was found, that Au (III) was significantly more toxic than AuNPs PVP and AuNPs CIT. AuNPs showed significant toxicity only at high concentrations (mg/L), which are not environmentally relevant in the present time, but a cautious approach is advised, due to the possibility of interactions with other contaminants.


Assuntos
Aliivibrio fischeri/efeitos dos fármacos , Araceae/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Ouro/toxicidade , Íons/toxicidade , Nanopartículas Metálicas/toxicidade , Peixe-Zebra , Animais , Organismos Aquáticos , Daphnia/embriologia , Relação Dose-Resposta a Droga , Embrião não Mamífero/efeitos dos fármacos , Testes de Toxicidade Aguda
6.
Ecotoxicol Environ Saf ; 203: 110934, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888599

RESUMO

Pharmaceuticals and personal care products are emerging contaminants that are increasingly detected in the environment worldwide. Certain classes of pharmaceuticals, such as selective serotonin reuptake inhibitors (SSRIs), are a major environmental concern due to their widespread use and the fact that these compounds are designed to have biological effects at low doses. A complication in predicting toxic effects of SSRIs in nontarget organisms is that their mechanism of action is not fully understood. To better understand the potential toxic effects of SSRIs, we employed an ultra-low input RNA-sequencing method to identify potential pathways that are affected by early exposure to two SSRIs (fluoxetine and paroxetine). We exposed wildtype zebrafish (Danio rerio) embryos to 100 µg/L of either fluoxetine or paroxetine for 6 days before extracting and sequencing mRNA from individual larval brains. Differential gene expression analysis identified 1550 genes that were significantly affected by SSRI exposure with a core set of 138 genes altered by both SSRIs. Weighted gene co-expression network analysis identified 7 modules of genes whose expression patterns were significantly correlated with SSRI exposure. Functional enrichment analysis of differentially expressed genes as well as network module genes repeatedly identified various terms associated with mitochondrial and neuronal structures, mitochondrial respiration, and neurodevelopmental processes. The enrichment of these terms indicates that toxic effects of SSRI exposure are likely caused by mitochondrial dysfunction and subsequent neurodevelopmental effects. To our knowledge, this is the first effort to study the tissue-specific transcriptomic effects of SSRIs in developing zebrafish, providing specific, high resolution molecular data regarding the sublethal effects of SSRI exposure.


Assuntos
Encéfalo/efeitos dos fármacos , Larva/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Inibidores de Captação de Serotonina/toxicidade , Transcriptoma/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Animais , Encéfalo/embriologia , Biologia Computacional , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Humanos , Larva/genética , Análise de Sequência de RNA , Peixe-Zebra/genética
7.
Ecotoxicol Environ Saf ; 203: 110946, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888619

RESUMO

Zebrafish embryos are highly sensitive to toxicant exposure and have been used to evaluate the potential eco-toxicity caused by organic pollutants in the aquatic environment. This study was to develop four quantitative structure-activity relationship (QSAR) models based on norm descriptors for acute toxicity of different exposure times toward zebrafish embryo of organic compounds with various structures. Norm descriptors were obtained by calculating the norm index of the atomic distribution matrix, which was composed of atomic spatial distribution and atomic properties. These norm index-based QSAR models presented satisfactory results with R2 of 0.8549, 0.9162, 0.8335 and 0.8119 for 48, 96, 120 and 132 h, respectively. Validation results including cross validation, external validation, Y-randomized test and applicability domain analysis indicated that the proposed models were stable, robust and reliable. Accordingly, these norm descriptors might be effective in predicting the acute toxicity of various organics to zebrafish embryos, which might be useful for evaluating the potential hazards of organic pollutants to aquatic environment.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Compostos Orgânicos , Relação Quantitativa Estrutura-Atividade , Peixe-Zebra , Animais , Compostos Orgânicos/química , Compostos Orgânicos/toxicidade , Testes de Toxicidade Aguda
8.
Chemosphere ; 254: 126900, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32957295

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants in marine environments and have arouse great concern since they pose adverse effects to marine ecosystem. To determine the potential impacts of environmentally relevant PAHs on early life stages of marine fish, this study exposed embryos of marine medaka (Oryzias melastigma) to 0, 2, 10, 50, and 250 µg/L of phenanthrene (Phe), one of the most abundant PAHs. The results demonstrated that Phe exposure decreased hatching rates, delayed hatching time of embryos, and increased deformity rate of newly-hatched larvae. Exposure to 10 and 50 µg/L Phe decreased the survival rate of marine medaka larvae at 28 days post-fertilization (dpf), and no embryo successfully hatched in 250 µg/L Phe exposure group. Morphology results showed that 10, 50, and 250 µg/L Phe exposure significantly retarded the development of embryos, and 2, 10, and 50 µg/L caused yolk sac edema and pericardial edema in newly-hatched larvae, indicating that low concentrations of Phe could induce developmental cardiac toxicity. Furthermore, the changes in the expression of heart development-related genes were determined, and the results showed that Phe-induced cardiac malformation might be related with fgf8, bmp4, smyd1, ATPase and gata4 genes. Overall, environmentally relevant PAHs could disrupt heart morphogenesis and hatching process of marine medaka, which might have profound consequences for sustainability of fish population.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Oryzias/crescimento & desenvolvimento , Fenantrenos/toxicidade , Teratogênios/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Ecossistema , Embrião não Mamífero/anormalidades , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Coração/efeitos dos fármacos , Coração/embriologia , Larva/efeitos dos fármacos , Larva/genética , Oryzias/genética , Fenantrenos/análise , Teratogênios/análise , Poluentes Químicos da Água/análise
9.
Ecotoxicol Environ Saf ; 202: 110936, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800219

RESUMO

Developmental toxicity refers to the occurrence of adverse effects on a developing organism as a consequence of exposure to hazardous chemicals. The assessment of developmental toxicity has become relevant to the safety assessment process of chemicals. The zebrafish embryo developmental toxicology assay is an emerging test used to screen the teratogenic potential of chemicals and it is proposed as a promising test to replace teratogenic assays with animals. Supported by the increased availability of data from this test, the developmental toxicity assay with zebrafish has become an interesting endpoint for the in silico modelling. The purpose of this study was to build up quantitative structure-activity relationship (QSAR) models. In this work, new in silico models for the evaluation of developmental toxicity were built using a well-defined set of data from the ToxCastTM Phase I chemical library on the zebrafish embryo. Categorical and continuous QSAR models were built by gradient boosting machine learning and the Monte Carlo technique respectively, in accordance with Organization for Economic Co-operation and Development principles and their statistical quality was satisfactory. The classification model reached balanced accuracy 0.89 and Matthews correlation coefficient 0.77 on the test set. The regression model reached correlation coefficient R2 0.70 in external validation and leave-one-out cross-validated Q2 0.73 in internal validation.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Testes de Toxicidade/métodos , Poluentes Químicos da Água/toxicidade , Animais , Simulação por Computador , Substâncias Perigosas , Aprendizado de Máquina , Relação Quantitativa Estrutura-Atividade , Teratogênios , Peixe-Zebra/embriologia
10.
Ecotoxicol Environ Saf ; 202: 110909, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800244

RESUMO

The presence of mycotoxins in food has created concern. Mycotoxin prevalence in our environment has changed in the last few years maybe due to climatic and other environmental changes. Evidence has emerged from in vitro and in vivo models: some mycotoxins have been found to be potentially carcinogenic, embryogenically harmful, teratogenic, and to generate nephrotoxicity. The risk assessment of exposures to mycotoxins at early life stages became mandatory. In this regard, the effects of toxic compounds on zebrafish have been widely studied, and more recently, mycotoxins have been tested with respect to their effects on developmental and teratogenic effects in this model system, which offers several advantages as it is an inexpensive and an accessible vertebrate model to study developmental toxicity. External post-fertilization and quick maturation make it sensitive to environmental effects and facilitate the detection of endpoints such as morphological deformities, time of hatching, and behavioral responses. Therefore, there is a potential for larval zebrafish to provide new insights into the toxicological effects of mycotoxins. We provide an overview of recent mycotoxin toxicological research in zebrafish embryos and larvae, highlighting its usefulness to toxicology and discuss the strengths and limitations of this model system.


Assuntos
Micotoxinas/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Animais , Embrião não Mamífero/efeitos dos fármacos , Larva/efeitos dos fármacos , Teratogênios/toxicidade
11.
Ecotoxicol Environ Saf ; 202: 110922, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800257

RESUMO

Fluorene-9-bisphenol (BHPF) is a substitute for bisphenol A (BPA), which is widely used to manufacture plastic products. Previous studies indicate that BHPF has an anti-estrogenic effect and induces cytotoxicity in mice oocytes. However, the effects of acute BHPF exposure on the aquatic organism obtain little attention. In this study, a series of BHPF concentrations (1 µM, 2 µM, 5 µM, 10 µM, 20 µM) was used to exposed zebrafish embryos from 2 h post-fertilization (hpf). The results showed the LC50 at 96hpf was 2.88 µM (1.01 mg/L). Acute exposure induced malformation in morphology, and retarded epiboly rate at 10hpf, increased apoptosis. Moreover, acute BHPF exposure led cardiotoxicity, by impeding cardiac looping, decreasing cardiac contractility (reducing the stroke volume and cardiac output, decreasing fractional shortening of ventricle). Besides that, BHPF exposure altered the expression of cardiac transcriptional regulators and development related genes. In conclusion, acute BHPF exposure induced developmental abnormality, retarded cardiac morphogenesis and injured the cardiac contractility. This study indicated BHPF would be an unneglected threat for the safety of aquatic organisms.


Assuntos
Compostos Benzidrílicos/toxicidade , Fenóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Cardiotoxicidade/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Fluorenos/toxicidade , Camundongos , Oócitos/crescimento & desenvolvimento , Plásticos , Testes de Toxicidade Aguda , Poluentes Químicos da Água/metabolismo , Peixe-Zebra
12.
Ecotoxicol Environ Saf ; 204: 111068, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32745784

RESUMO

Herein, eight common endocrine disrupting chemicals (EDCs) were exposed to zebrafish (Danio rerio) to investigate the relationship between different EDCs and their activated estrogen receptors. Under acute exposure, we identified five major malformation types whose incidence and deformity modes differed among EDCs. Luciferase analysis divided the EDC receptors into four categories: (i) triclosan (TCS), 17ß-estradiol (E2) and estriol (E3) mainly activated GPER expression; (ii) bisphenol A (BPA), p-(tert-octyl) phenol (POP), 17α-ethynylestradiol (EE2), E2 and E3 activated ERß expression; (iii) E2 and E3 acted on both GPER and ERß; and (iv) estrone (E1) and 9,9-bis(4-hydroxyphenyl)fluorene (BHPF) had little effect on the two receptors. In vivo immunofluorescence experiments on 96-hpf larvae provided evidence that TCS and POP acted on GPER and ERß, respectively, while E2 acted on the two receptors simultaneously. Luciferase activities in the promoter regions of gper (-986 to -488) and erß (-1998 to -1496) were higher than those in other regions, identifying these key regions as targets for transcription activity. TCS promoted GPER expression by acting on the JUND transcription factor, while POP promoted ERß expression by activating the Foxl1 transcription factor. In contrast, E2 mainly regulated transcription of GPER and ERß by Arid3a. These findings provide compelling evidence that different EDCs possess varying estrogen receptors, leading to differential regulatory pathways and abnormality symptoms. These results offer an experimental strategy and fundamental information to assess the molecular mechanisms of EDC-induced estrogen effects.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Receptor beta de Estrogênio/metabolismo , Fenóis/toxicidade , Receptores Acoplados a Proteínas-G/metabolismo , Poluentes Químicos da Água/toxicidade , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Compostos Benzidrílicos/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Disruptores Endócrinos/metabolismo , Larva/efeitos dos fármacos , Larva/metabolismo , Fenóis/metabolismo , Poluentes Químicos da Água/metabolismo
13.
Int J Nanomedicine ; 15: 4091-4104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606666

RESUMO

Introduction: Humans are intentionally exposed to gold nanoparticles (AuNPs) where they are used in variety of biomedical applications as imaging and drug delivery agents as well as diagnostic and therapeutic agents currently in clinic and in a variety of upcoming clinical trials. Consequently, it is critical that we gain a better understanding of how physiochemical properties such as size, shape, and surface chemistry drive cellular uptake and AuNP toxicity in vivo. Understanding and being able to manipulate these physiochemical properties will allow for the production of safer and more efficacious use of AuNPs in biomedical applications. Methods and Materials: Here, AuNPs of three sizes, 5 nm, 10 nm, and 20 nm, were coated with a lipid bilayer composed of sodium oleate, hydrogenated phosphatidylcholine, and hexanethiol. To understand how the physical features of AuNPs influence uptake through cellular membranes, sum frequency generation (SFG) was utilized to assess the interactions of the AuNPs with a biomimetic lipid monolayer composed of a deuterated phospholipid 1.2-dipalmitoyl-d62-sn-glycero-3-phosphocholine (dDPPC). Results and Discussion: SFG measurements showed that 5 nm and 10 nm AuNPs are able to phase into the lipid monolayer with very little energetic cost, whereas, the 20 nm AuNPs warped the membrane conforming it to the curvature of hybrid lipid-coated AuNPs. Toxicity of the AuNPs were assessed in vivo to determine how AuNP curvature and uptake influence cell health. In contrast, in vivo toxicity tested in embryonic zebrafish showed rapid toxicity of the 5 nm AuNPs, with significant 24 hpf mortality occurring at concentrations ≥20 mg/L, whereas the 10 nm and 20 nm AuNPs showed no significant mortality throughout the five-day experiment. Conclusion: By combining information from membrane models using SFG spectroscopy with in vivo toxicity studies, a better mechanistic understanding of how nanoparticles (NPs) interact with membranes is developed to understand how the physiochemical features of AuNPs drive nanoparticle-membrane interactions, cellular uptake, and toxicity.


Assuntos
Membrana Celular/química , Ouro/toxicidade , Lipídeos/química , Membranas Artificiais , Nanopartículas Metálicas/toxicidade , Tamanho da Partícula , Testes de Toxicidade , Animais , Embrião não Mamífero/anormalidades , Embrião não Mamífero/efeitos dos fármacos , Humanos , Espectrofotometria Ultravioleta , Análise Espectral , Peixe-Zebra/embriologia
14.
Int J Nanomedicine ; 15: 4407-4415, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606685

RESUMO

Objective: Silica nanoparticles (SiO2 NPs) have been extensively employed in biomedical field. SiO2 NPs are primarily designed to enter the circulatory system; however, little information is available on potential adverse effects of SiO2 NPs on the nervous system. Methods: The neurotoxicity of SiO2 NPs at different concentrations (3, 6, 12 ng/nL) on zebrafish embryos was determined using immunofluorescence and microarray techniques, and subsequently confirmed by qRT-PCR. Results: SiO2 NPs disrupt the axonal integrity and decrease the length of axons in Tg (NBT: EGFP) transgenic lines. The number of apoptotic cells in the brain and central nervous system of zebrafish embryos was increased in the presence of 12 ng/nL of SiO2 NPs, but the difference did not reach statistical significance. Screening for changes in the expression of genes involved in the neuroactive ligand-receptor interaction pathway was performed by microarray and confirmed by qRT-PCR. These analyses demonstrated that SiO2 NPs markedly downregulated genes associated with neural function (grm6a, drd1b, chrnb3b, adrb2a, grin2ab, npffr2.1, npy8br, gabrd, chrma3, gabrg3, gria3a, grm1a, adra2b, and glra3). Conclusion: The obtained results documented that SiO2 NPs can induce developmental neurotoxicity by affecting the neuroactive ligand-receptor interaction signaling pathway. This new evidence may help to clarify the mechanism of SiO2 NPs-mediated neurotoxicity.


Assuntos
Embrião não Mamífero/metabolismo , Nanopartículas/toxicidade , Neurotoxinas/toxicidade , Receptores de Superfície Celular/metabolismo , Transdução de Sinais , Dióxido de Silício/toxicidade , Peixe-Zebra/embriologia , Animais , Apoptose/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Ligantes , Transdução de Sinais/efeitos dos fármacos
15.
Aquat Toxicol ; 226: 105560, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32659603

RESUMO

Triclosan (TCS) is commonly used in home and personal care products (HPCPs), which causes it to be ubiquitously detected in aquatic environments. The toxicity of triclosan to aquatic organisms can vary at different pH values because the ionization states of TCS affect its bioaccumulation properties. The objective of this study was to examine the pH-dependent toxicity of TCS on embryonic zebrafish (Danio rerio) using a metabolomic profiling method based on gas chromatography-mass spectrometry (GC-MS). Exposure experiments were conducted on zebrafish embryos at three pH conditions (6, 7, and 8) and two TCS concentrations (30 µg/L and 300 µg/L). Metabolic profiles were obtained by extracting intracellular metabolites. Univariate (One-way ANOVA) and multivariate (PLS-DA) analyses were conducted to determine the metabolomic changes in TCS-treated embryos. Changes in the metabolic profile revealed that interference in biological pathways were induced by mostly ionized TCS (low pH) and high TCS concentrations. Also, fold changes in metabolite profiles showed that the TCS toxicity was a function of pH. Metabolites including urea, D-glucose, D-galactose, phenylalanine, L-glutamic acid, citric acid, and phosphoric acid showed significant changes under different pH conditions (p-value < 0.05). Our metabolomics study revealed that the responses of metabolites to TCS toxicity were pH-dependent. The differences of the responses could be attributed to the bioaccumulation capability of TCS, which increased as the ionized TCS proportion increased under low pH conditions.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Triclosan/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Embrião não Mamífero/metabolismo , Concentração de Íons de Hidrogênio , Metabolômica/métodos , Peixe-Zebra/crescimento & desenvolvimento
16.
Aquat Toxicol ; 226: 105562, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32668346

RESUMO

Fish are exposed to steroids of different classes in contaminated waters, but their effects are not sufficiently understood. Here we employed an anti-sense technique using morpholino oligonucleotides to knockdown the glucocorticoid receptors (GRs, GRα and GRß) and androgen receptor (AR) to investigate their role in physiological and transcriptional responses. To this end, zebrafish embryos were exposed to clobetasol propionate (CLO), androstenedione (A4) and mixtures containing different classes of steroids. CLO caused a decrease of spontaneous muscle contraction and increase of heart rate, as well as transcriptional induction of pepck1, fkbp5, sult2st3 and vitellogenin (vtg1) at 24 and/or 48 h post fertilization (hpf). Knockdown of GRs eliminated these effects, while knockdown of AR decreased the ar transcript but caused no expressional changes, except induction of sult2st3 after exposure to A4 at 24 hpf. Exposure to a mixture of 6 steroids comprising progesterone (P4) and three progestins, cyproterone acetate, dienogest, drospirenone, 17ß-estradiol (E2) and CLO caused a significant induction of pepck1, sult2st3, vtg1 and per1a. Knockdown of GRs eliminated the physiological effects and the up-regulation of vtg1, sult2st3, pepck1, fkbp5 and per1a. Thus, as with CLO, responses in mixtures were regulated by GRs independently from the presence of other steroids. Exposure to a mixture comprising A4, CLO, E2 and P4 caused induction of vtg1, cyp19b, sult2st3 and fkbp5. Knockdown of AR had no effect, indicating that regulation of these genes occurred by the GRs and estrogen receptor (ER). Our findings show that in early embryos GRs cause vtg1 and sult2st3 induction in addition to known glucocorticoid target genes. Each steroid receptor regulated its own target genes in steroid mixtures independently from other steroids. However, enhanced expressional induction occurred for vtg1 and fkbp5 in steroid mixtures, indicating an interaction/cross-talk between GRs and ER. These findings have importance for the understanding of molecular effects of steroid mixtures.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Receptores de Glucocorticoides/metabolismo , Esteroides/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Receptores Androgênicos/genética , Receptores de Glucocorticoides/genética , Transdução de Sinais , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento
17.
Aquat Toxicol ; 226: 105558, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32673888

RESUMO

The aryl hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that mediates the toxicity of dioxins and dioxin-like compounds (DLCs) in vertebrates. Two clades of the Ahr family exist in teleosts (Ahr1 and Ahr2), and it has been demonstrated that Ahr2 is the main protein involved in mediating the toxicity of dioxins and DLCs in most teleost species. Recently, we characterized the Atlantic cod (Gadus morhua) Ahr1a and Ahr2a receptors. To further explore a possible subfunction partitioning of Ahr1a and Ahr2a in Atlantic cod we have mapped the expression and localization of ahr1a and ahr2a in early developmental stages. Atlantic cod embryos were continuously exposed in a passive-dosing exposure system to the Ahr agonist, benzo[a]pyrene (B[a]P), from five days post fertilization (dpf) until three days post hatching (dph). Expression of ahr1a, ahr2a, and the Ahr-target genes, cyp1a and ahrrb, was assessed in embryos (8 dpf and 10 dpf) and larvae (3 dph) with quantitative real-time PCR analyses (qPCR), while in situ hybridization was used to assess the localization of expression of ahr1a, ahr2a and cyp1a. Quantitative measurements showed an increased cyp1a expression in B[a]P-exposed samples at all sampling points, and for ahr2a at 10 dpf, confirming the activation of the Ahr-signalling pathway. Furthermore, B[a]P strongly induced ahr2a and cyp1a expression in the cardiovascular system and skin, respectively, of embryos and larvae. Induced expression of both ahr2a and cyp1a was also revealed in the liver of B[a]P-exposed larvae. Our results suggest that Ahr2a is the major subtype involved in mediating responses to B[a]P in early developmental stages of Atlantic cod, which involves transcriptional regulation of biotransformation genes, such as cyp1a. The focused expression of ahr1a in the eye of embryos and larvae, and the presence of ahr2a transcripts in the jaws and fin nodes, further indicate evolved specialized roles of the two Ahrs in ontogenesis.


Assuntos
Citocromo P-450 CYP1A1/metabolismo , Gadus morhua/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Benzo(a)pireno/toxicidade , Citocromo P-450 CYP1A1/genética , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Olho/efeitos dos fármacos , Olho/embriologia , Olho/metabolismo , Gadus morhua/genética , Gadus morhua/metabolismo , Larva/efeitos dos fármacos , Larva/genética , Fígado/efeitos dos fármacos , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Poluentes Químicos da Água/toxicidade
18.
Chemosphere ; 259: 127380, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32634720

RESUMO

Fomesafen is widely used in agriculture and can be detected in the environment and agricultural products. Research on the developmental toxicity of fomesafen in animals is currently very limited. Here, we used zebrafish as an animal model to evaluate the toxicity of fomesafen in developing aquatic vertebrates and higher animals. From 6h to 72h following fertilization, exposure of zebrafish embryos to 5, 10 and 20 mg/L of fomesafen resulted in pericardial edema, a reduction in heart rate, shortening of body length, and yolk sac edema. Fomesafen reduced the number of immune cells such as neutrophils and macrophages, increased the expression of a number of inflammatory factors, induced the up-regulation of the oxidative stress response and apoptosis, and disrupted the activity of enzymes related to nerve development, which affected the motility of the embryos. In conclusion, the results provide new evidence for the comprehensive assessment of fomesafen toxicity in aquatic vertebrates.


Assuntos
Benzamidas/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Herbicidas/toxicidade , Animais , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Regulação para Cima , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
19.
Aquat Toxicol ; 225: 105525, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32629302

RESUMO

Halogenated dipeptides, 3, 5-di-I-tyrosylalanine (DIYA), have been identified as novel disinfection byproducts (DBPs), following chloramination of authentic water. However, little is known about their toxicity. Zebrafish embryos were used to assess the toxicity of novel iodinated DBPs (I-DBPs). Although DIYA did not exhibit high acute toxicity to embryonic zebrafish (LC50 > 2 mM), it significantly inhibited pigmentation of melanophores and xanthophores on head, trunk and tail at 500 µM as determined by photographic analysis. Whereas N-phenylthiourea (PTU) as a pigment inhibitor did not inhibit development of yellow pigments. Colorimetric detection of melanin further confirmed these results. Quantitative real time polymerase chain reaction (qRT-PCR) measurements indicated that genes (dct, slc24a5, tyr, tyrp1a, tyrp1b, silva) associated with the melanogenesis pathway were dramatically down-regulated following exposure to 500 µM DIYA. In addition, enzymatic activity of tyrosinase (TYR) decreased, also demonstrating that the underlying mechanism of hypopigmentation was attributed to the disruption of melanogenesis pathway. Transcription levels of xanthophore genes (gch2, bnc2, csf1a, csf1b, pax7a and pax7b) were also monitored by qRT-PCR assay. DIYA exposure up-regulated expression of gch2 and bnc2, but not csf1 and pax7. Tested DIYA analogues, brominated tyrosine was unlikely to inhibit pigmentation, indicating that the iodine substitution and dipeptides structure are of important structural feature for the inhibition of pigmentation. In this study, we observed that DIYA inhibited melanogenesis related genes, which might contribute to pigmentation defects. Moreover, as an emerging I-DBPs, the developmental toxicity of aromatic dipeptides should be further studied.


Assuntos
Dipeptídeos/toxicidade , Desinfetantes/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Hipopigmentação/induzido quimicamente , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Embrião não Mamífero/metabolismo , Expressão Gênica/efeitos dos fármacos , Halogenação , Hipopigmentação/genética , Melanóforos/efeitos dos fármacos , Melanóforos/metabolismo , Purificação da Água , Proteínas de Peixe-Zebra/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-32617729

RESUMO

Some species of fish have been used as bioindicators of aquatic environmental pollution all over the world. Pejerrey (Odontesthes bonariensis) was selected for the current study due to its sensitivity to pollutants and because is one of the emblematic fish species that inhabits shallow lakes of the Pampa region (Argentina). Recently, in Chascomús lake were recorded concentrations of Cd, Cr, Cu and Zn with values above the Argentine National Guidelines for the Protection of the Aquatic life. Regarding this, the aim of the present study was to investigate the effects of environmental concentrations of these metals on the sperm quality, fertilization and hatching rates, and embryo and larval survival of pejerrey. Also, the same endpoints were analyzed with concentrations ten times higher to simulate a polluted worst-case scenario. The results showed that the presence of some metals in aquatic environments reduced pejerrey sperm motility (in ~50%) and velocity (in ~30%). These results were obtained using a computer assisted sperm analyzer enforcing the application of this analysis as a tool or bioindicator of aquatic pollution. In addition, fertilization rate was diminished (in ~40%) for all treatments. Besides, the hatching rate, and embryo and larval survival were drastically affected being zero for the highest metal concentrations assessed. All together these results, showed that even lower metal concentrations can negatively affect different reproductive parameters of one of the most emblematic fish species of the Argentinean water bodies.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Fertilização/efeitos dos fármacos , Metais Pesados/efeitos adversos , Smegmamorpha/fisiologia , Espermatozoides/efeitos dos fármacos , Poluentes Químicos da Água/efeitos adversos , Animais , Desenvolvimento Embrionário/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Masculino , Análise do Sêmen/veterinária
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA