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1.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2610-2613, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018541

RESUMO

The zebrafish model has been demonstrated as an ideal vertebrate model system for a diverse range of biological studies. Along with conventional approaches, monitoring and analysis of zebrafish electrocardiogram (ECG) have been utilized for cardio-physiological screening and elucidation. ECG monitoring has been carried out with fish treated with anesthetic drugs, rendering the short period of time in recording the signals (<5 min). In this work, a prolonged sedation system for continuous ECG monitoring of multiple zebrafish was proposed and developed. We built a circulation system to provide prolonged mild anesthesia which allows more consistent and intrinsic ECG measurement. The use of prolonged anesthesia helped reduce the concentration of the anesthetic drug (MS222 or Tricaine) from 200 mg/L to 100 mg/L and even lower; thus, maintaining the integrity of intrinsic ECG. Moreover, heartrate variation during recording was investigated, showing minute changes (±3.2 beats per minute - BPM). The development of this prolonged ECG monitoring system would open the possibility of long-term monitoring for studies such as drug screening and forward genetic screening.


Assuntos
Anestesia , Anestesiologia , Animais , Eletrocardiografia , Frequência Cardíaca , Peixe-Zebra
2.
Sci Total Environ ; 746: 141860, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33027873

RESUMO

Tralopyril, an antifouling biocide, widely used in antifouling systems to prevent underwater equipment from biological contamination, which can pose a potential risk to aquatic organisms and human health. However, there is little information available on the toxicity of tralopyril to aquatic organisms. Herein, zebrafish (Danio rerio) were used to investigate the toxicity mechanisms of tralopyril and a series of developmental indicators, thyroid hormones, gene expression and metabolomics were measured. Results showed that tralopyril significantly decreased the heart-beat and body length of zebrafish embryos-larvae exposed to 4.20 µg/L or higher concentrations of tralopyril and also induced developmental defects including pericardial hemorrhage, spine deformation, pericardial edema, tail malformation and uninflated gas bladder. Tralopyril decreased the thyroid hormone concentrations in embryos and changed the transcriptions of the related genes (TRHR, TSHß, TSHR, Nkx2.1, Dio1, TRα, TRß, TTR and UGT1ab). Additionally, metabolomics analysis showed that tralopyril affected the metabolism of amino acids, energy and lipids, which was associated with regulation of thyroid system. Furthermore, this study demonstrated that alterations of endogenous metabolites induced the thyroid endocrine disruption in zebrafish following the tralopyril treatment. Therefore, the results showed that tralopyril can induce adverse developmental effects on zebrafish embryos by disrupting the thyroid system and metabolism.


Assuntos
Glândula Tireoide , Peixe-Zebra , Animais , Pirróis , Hormônios Tireóideos
3.
Aquat Toxicol ; 227: 105595, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32911330

RESUMO

In order to understand the potential impacts of nickel nanowires (Ni NWs) after reaching the aquatic environment, this research evaluated the toxicity of Ni NWs with different lengths (≤ 1.1, ≤11 and ≤ 80 µm) for several floating, planktonic and nektonic freshwater organisms. In this work, Ni NWs were synthesized by electrodeposition using anodized aluminum oxide (AAO) membranes. The toxicity of the NWs was assessed using a battery of aquatic species representative of key functions at the ecosystem level: the bacterium Aliivibrio fischeri, the algae Raphidocelis subcapitata, the macrophyte Lemna minor, the crustacean Daphnia magna and the zebrafish Danio rerio. Results indicated that for the concentrations tested (up to 2.5 mg L-1) the synthesized Ni NWs showed low toxicity. And although no lethal toxicity was observed for D. magna, at a sublethal level the feeding activity of the freshwater cladoceran was severely affected after exposure to Ni NWs. These findings showed that NWs can be accumulated in the gut of D. magna, even during a short exposure (24 h) directly impairing Daphnia nutrition and eventually populations growth. Consequently, this can also contribute to trophic transfer of NWs along the food chain. According to our results the toxicity of Ni NW may be mainly attributed to physical effects rather than chemical effects of Ni ions, considering that the concentrations of Ni NWs tested in this study were well below the toxicity thresholds reported in the literature for Ni ions and for Ni NMs.


Assuntos
Organismos Aquáticos/efeitos dos fármacos , Nanofios/toxicidade , Níquel/toxicidade , Purificação da Água/métodos , Aliivibrio fischeri , Animais , Clorofíceas , Daphnia/efeitos dos fármacos , Ecossistema , Cadeia Alimentar , Água Doce , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
4.
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
5.
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
6.
Chemosphere ; 254: 126608, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32957262

RESUMO

Al2O3 Nanoparticles (Al2O3-NPs) have been widely used because of their unique physical and chemical properties, and Al2O3-NPs can be released into the environment directly or indirectly. Our previous research found that 13 nm Al2O3-NPs can induce neural cell death and autophagy in primarily cultured neural cells in vitro. The aim of this study was to determine where Al2O3-NPs at 13 nm particle size can cause neural cells in vivo and assess related behavioural changes and involved potential mechanisms. Zebrafish from embryo to adult were selected as animal models. Learning and memory as functional indicators of neural cells in zebrafish were measured during the development from embryo to adult. Our results indicate that Al2O3-NPs treatment in zebrafish embryos stages can cause the accumulation of aluminium content in zebrafish brain tissue, leading to progressive impaired neurodevelopmental behaviours and latent learning and memory performance. Additionally, oxidative stress and disruption of dopaminergic transmission in zebrafish brain tissues are correlated with the dose-dependent and age-dependent accumulation of aluminium content. Moreover, the number of neural cells in the telencephalon tissue treated with Al2O3-NPs significantly declined, and the ultramicroscopic morphology indicated profound autophagy alternations. The results suggest that Al2O3-NPs has dose-dependent and time-dependent progressive damage on learning and memory performance in adult zebrafish when treated in embryos. This is the first study of the effects of Al2O3-NPs on learning and memory during the development of zebrafish from embryo to adult.


Assuntos
Óxido de Alumínio/toxicidade , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Nanopartículas/toxicidade , Alumínio/farmacologia , Óxido de Alumínio/química , Animais , Embrião não Mamífero , Nanopartículas Metálicas , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Peixe-Zebra/embriologia
7.
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
8.
Elife ; 92020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32902382

RESUMO

Mutant zebrafish exhibit different behaviours depending on the genetic background of the fish they were raised with.


Assuntos
Ocitocina , Receptores de Ocitocina , Animais , Reconhecimento Psicológico , Comportamento Social , Peixe-Zebra
9.
Ecotoxicol Environ Saf ; 203: 111014, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888589

RESUMO

Tributyltin (TBT), a widely and persistently distributed organontin, has been well documented to disrupt reproduction and behaviors in animals due to its anti-aromatase activity. TBT has been also reported to enhance anxiety in several fish species, whereas the mechanism underlying remains largely unknown. To investigate the disruption of TBT on fish anxiety and the mechanisms possibly involved, adult male zebrafish (Danio rerio) were treated with TBT (100 and 500 ng/L) for 28 days and anxiety behavior was further investigated using a novel tank dive test. Result showed that TBT treatment significantly enhanced the total time of the fish spent in the lower half, delayed the onset time to the higher half of the tank and increased the total duration of freezing of the fish, indicating an enhanced anxiety in TBT-treated fish. Accordingly, TBT sharply elevated the cortisol levels in plasma in a concentration-dependent manner, suggesting that the elevated cortisol level might be involved in the enhanced anxiety. Although the expression of crha was significantly increased and crhbp was significantly decreased in the brain of TBT-treated fish which is consistent to the elevated cortisol level, the expressions of actha and acthb were sharply down-regulated. In contrast, the expressions of genes responsible for the synthesis and action of serotonin (5-HT) (pet1, thp2 and htr1aa), dopamine (DA) (th1, slc6a3, drd2a and drd2b) and gamma-aminobutyric acid (GABA) (gad2 and gabrg2) were all significantly inhibited. The down-regulation of these pivotal genes acting in 5-HT, DA and GABA neurotransmitter systems in response to TBT corresponded well with the TBT-enhanced anxiety in fish. It was thus strongly suggested that these neurotransmitters might be also involved in TBT-enhanced anxiety in adult male zebrafish. The present study extended our understanding of the neurotoxicity of TBT on the anxiety control and behavioral modulation in fish.


Assuntos
Ansiedade/induzido quimicamente , Hidrocortisona/metabolismo , Neurotransmissores/metabolismo , Compostos de Trialquitina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Dopamina/metabolismo , Masculino , Serotonina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra/metabolismo , Ácido gama-Aminobutírico/metabolismo
10.
Nat Commun ; 11(1): 4505, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908148

RESUMO

Evidence for transgenerational inheritance of epigenetic information in vertebrates is scarce. Aberrant patterns of DNA methylation in gametes may set the stage for transmission into future generations. Here, we describe a viable hypomorphic allele of dnmt1 in zebrafish that causes widespread demethylation of CpG dinucleotides in sperm and somatic tissues. We find that homozygous mutants are essentially normal, with the exception of drastically impaired lymphopoiesis, affecting both larval and adult phases of T cell development. The phenotype of impaired larval (but not adult) T cell development is transmitted to subsequent generations by genotypically wildtype fish. We further find that about 200 differentially methylated regions in sperm DNA of transmitting and non-transmitting males, including hypermethylated sites associated with runx3 and rptor genes, whose reduced activities are associated with impaired larval T cell development. Our results indicate a particular sensitivity of larval T cell development to transgenerationally inherited epimutations.


Assuntos
Diferenciação Celular/genética , Genes Recessivos , Larva/crescimento & desenvolvimento , Linfopoese/genética , Linfócitos T/fisiologia , Alelos , Animais , Animais Geneticamente Modificados , Subunidade alfa 3 de Fator de Ligação ao Core/genética , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Metilação de DNA , Epigênese Genética , Feminino , Genética , Larva/citologia , Masculino , Mutação , Proteína Regulatória Associada a mTOR/genética , Espermatozoides/metabolismo , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
11.
Ecotoxicol Environ Saf ; 205: 111348, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979803

RESUMO

Transgenerational effects induced by environmental stressors are a threat to ecosystems and human health. However, there is still limited observation and understanding of the potential of chemicals to influence life outcomes over several generations. In the present study, we investigated the effects of two environmental contaminants, coumarin 47 and permethrin, on exposed zebrafish (F0) and their progeny (F1-F3). Coumarin 47 is commonly found in personal care products and dyes, whereas permethrin is used as a domestic and agricultural pyrethroid insecticide/insect repellent. Zebrafish (F0) were exposed during early development until 28 days post-fertilization and their progeny (F1-F3) were bred unexposed. On one hand, the effects induced by coumarin 47 suggest no multigenerational toxicity. On the other hand, we found that behavior of zebrafish larvae was significantly affected by exposure to permethrin in F1 to F3 generations with some differences depending on the concentration. This suggests persistent alteration of the neural or neuromuscular function. In addition, lipidomic analyses showed that permethrin treatment was partially correlated with lysophosphatidylcholine levels in zebrafish, an important lipid for neurodevelopment. Overall, these results stress out one of the most widely used pyrethroids can trigger long-term, multi- and possibly transgenerational changes in the nervous system of zebrafish. These neurobehavioral changes echo the effects observed under direct exposure to high concentrations of permethrin and therefore call for more research on mechanisms underlying effect inheritance.


Assuntos
Cumarínicos/toxicidade , Repelentes de Insetos/toxicidade , Permetrina/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Cumarínicos/metabolismo , Ecossistema , Fertilidade/efeitos dos fármacos , Larva/efeitos dos fármacos , Metabolismo dos Lipídeos , Peixe-Zebra/metabolismo , Peixe-Zebra/fisiologia
12.
Anticancer Res ; 40(9): 5049-5057, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878793

RESUMO

BACKGROUND/AIM: Studies with acridine compounds have reported anticancer effects. Herein, we evaluated the toxicity and antitumor effect of the (E)-1'-((4-chlorobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-06), a promising anticancer spiro-acridine compound. MATERIALS AND METHODS: The toxicity of AMTAC-06 was evaluated on zebrafish and mice. Antitumor activity was assessed in Ehrlich ascites carcinoma model. Effects on angiogenesis, cytokine levels and cell cycle were also investigated. RESULTS: AMTAC-06 did not induce toxicity on zebrafish and mice (LD50 approximately 5000 mg/kg, intraperitoneally). No genotoxicity was observed on micronucleus assay. AMTAC-06 significantly reduced the total viable Ehrlich tumor cells and increased sub-G1 peak, suggesting apoptosis was triggered. Moreover, the compound significantly decreased the density of peritumoral microvessels, indicating an anti-angiogenic action, possibly dependent on the cytokine modulation (TNF-α, IL-1ß and IFN-γ). No significant toxicological effects were recorded for AMTAC-06 on tumor transplanted animals. CONCLUSION: AMTAC-06 has low toxicity and a significant antitumor activity.


Assuntos
Acridinas/farmacologia , Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Fatores Imunológicos/farmacologia , Compostos de Espiro/farmacologia , Acridinas/química , Inibidores da Angiogênese/química , Animais , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Fatores Imunológicos/química , Imunomodulação/efeitos dos fármacos , Camundongos , Estrutura Molecular , Compostos de Espiro/química , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
13.
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
14.
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
15.
Sci Total Environ ; 741: 140450, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32886985

RESUMO

Surfactants are widely used in the industry of detergents, household products, and cosmetics. SAPDMA is a cationic surfactant that is used mostly in cosmetics, conditioning agents and has recently gained attention as a corrosion inhibitor in the sea pipelines industry. In this regard, literature concerning the ecotoxicological classification of SAPDMA on aquatic animals is lacking. This study aims to evaluate the potential ecotoxicity of SAPDMA using the aquatic zebrafish embryo model. The potential toxic effects of SAPDMA were assessed by different assays. This includes (i) mortality/survival assay to assess the median lethal concentration (LC50); (ii) teratogenicity assay to assess the no observed effect concentration (NOEC); (iii) organ-specific toxicity assays including cardiotoxicity, neurotoxicity (using locomotion assay), hematopoietic toxicity (hemoglobin synthesis using o-dianisidine staining), hepatotoxicity (liver steatosis and yolk retention using Oil Red O (ORO) stain); (iv) cellular cytotoxicity (mitochondrial membrane potential) by measuring the accumulation of JC-1 dye into mitochondria. Exposure of embryos to SAPDMA caused mortality in a dose-dependent manner with a calculated LC50 of 2.3 mg/L. Thus, based on the LC50 value and according to the Fish and Wildlife Service (FWS) Acute Toxicity Rating Scale, SAPDMA is classified as "moderately toxic". The No Observed Effect Concentration (NOEC) concerning a set of parameters including scoliosis, changes in body length, yolk, and eye sizes was 0.1 mg/L. At the same NOEC concentration (0.1 mg/L), no organ-specific toxicity was detected in fish treated with SAPDMA, except hepatomegaly with no associated liver dysfunctions. However, higher SAPDMA concentrations (0.8 mg/L) have dramatic effects on zebrafish organ development (eye, heart, and liver development). Our data recommend a re-evaluation of the SAPDMA employment in the industry setting and its strictly monitoring by environmental and public health agencies.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Dimetilaminas , Embrião não Mamífero , Dose Letal Mediana , Tensoativos
16.
Elife ; 92020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32880576

RESUMO

A new zebrafish study identifies compounds that shield ears and kidneys against an anticancer drug.


Assuntos
Antineoplásicos , Cisplatino , Animais , Rim , Substâncias Protetoras , Peixe-Zebra
17.
Sci Total Environ ; 740: 140392, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32927558

RESUMO

Environmental pollution by the psychoactive drug diazepam (DZP) has been suggested to disrupt various behavioral traits of fishes. Exposure to DZP in natural waters may be of episodic duration, but there are few reports on the persistence of abnormal behaviors of fishes caused by such acute exposure. In the current study, we exposed juvenile zebrafish (Danio rerio) to sublethal doses of DZP (1200, 120, and 12 µg/L) for four days and evaluated their behavioral traits and brain γ-aminobutyric acid (GABA) levels at days 0 (i.e., immediately after the 4-day exposure), 7, and 21 of the recovery period. Exposure to DZP induced short-term impairment of swimming ability and two-fish interactions of zebrafish. In contrast, DZP induced persistent and/or delayed effects on locomotor activity of zebrafish, i.e., hypoactivity at 1200 µg/L and hyperactivity at 120 and 12 µg/L, that could be still observed on days 7 and/or 21 during the recovery period. DZP exposure also exhibited concentration-specific effects on brain GABA levels in zebrafish, i.e., decreased at 1200 µg/L and increased at 120 and 12 µg/L. Correlation analysis suggested that the changes in brain GABA levels may contribute to the persistence of abnormalities in the locomotor activity of zebrafish. Our findings suggest that zebrafish need a long time to recover from acute exposure to DZP, thus highlighting that the persistence of behavioral abnormalities induced by such psychoactive drugs should be considered in order to better assess their risks in natural ecosystems.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Encéfalo , Diazepam , Ecossistema , Ácido gama-Aminobutírico
18.
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
20.
Ecotoxicol Environ Saf ; 205: 111339, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32961491

RESUMO

Famoxadone-cymoxanil is a new protective and therapeutic fungicide, but little research has been done on it or its toxicity in aquatic organisms. In this study, we used zebrafish to investigate the cardiotoxicity of famoxadone-cymoxanil and the potential mechanisms involved. Zebrafish embryos were exposed to different concentrations of famoxadone-cymoxanil until 72 h post-fertilization (hpf), then changes of heart morphology in zebrafish embryos were observed. We also detected the levels of oxidative stress, myocardial-cell proliferation and apoptosis, ATPase activity, and the expression of genes related to the cardiac development and calcium-signaling pathway. After famoxadone-cymoxanil exposure, pericardial edema, cardiac linearization, and reductions in the heart rate and cardiac output positively correlated with concentration. Although myocardial-cell apoptosis was not detected, proliferation of the cells was severely reduced and ATPase activity significantly decreased, resulting in a severe deficiency in heart function. In addition, indicators of oxidative stress changed significantly after exposure of the embryos to the fungicide. To better understand the possible molecular mechanisms of cardiovascular toxicity in zebrafish, we studied the transcriptional levels of cardiac development, calcium-signaling pathways, and genes associated with myocardial contractility. The mRNA expression levels of key genes in heart development were significantly down-regulated, while the expression of genes related to the calcium-signaling pathway (ATPase [atp2a1], cardiac troponin C [tnnc1a], and calcium channel [cacna1a]) was significantly inhibited. Expression of klf2a, a major endocardial flow-responsive gene, was also significantly inhibited. Mechanistically, famoxadone-cymoxanil toxicity might be due to the downregulation of genes associated with the calcium-signaling pathway and cardiac muscle contraction. Our results found that famoxadone-cymoxanil exposure causes cardiac developmental toxicity and severe energy deficiency in zebrafish.


Assuntos
Acetamidas/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Coração/efeitos dos fármacos , Estrobilurinas/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/genética , Cardiotoxicidade , Regulação para Baixo , Embrião não Mamífero/metabolismo , Embrião não Mamífero/patologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Coração/embriologia , Frequência Cardíaca/efeitos dos fármacos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
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