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1.
Environ Res ; 258: 119282, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823611

RESUMO

The Villa Victoria dam is one of the most important storage reservoirs in Mexico since it distributes water to more than 20 million inhabitants in the Metropolitan Zone of Mexico City. In this dam, the common carp (Cyprinus carpio) is an important food resource for the inhabitants, so the aim of this work was to evaluate the oxidative damage (lipoperoxidation, oxidized proteins, antioxidant enzymes activity and gene expression), AChE, embryotoxicity and behavioral changes in C. carpio embryos and larvae exposed to water from Villa Victoria dam for 24, 48, 72 and 96 h. The embryotoxicity was evaluated trough the General Morphology Score (GMS) and the teratogenic index. Behavioral changes in basal locomotor activity and thigmotaxis were evaluated in a DanioVision, Noldus ™. An increase in lipid and protein oxidation as well as modification of CAT, SOD and GPx enzymatic activity was observed during the exposure times. The GMS indicated a low development in the embryos, the teratogenic index was less than 1, however teratogenic effects as yolk edema, fin malformation, head malformation and scoliosis were observed. In parallel, an increase in AChE activity and gene expression was observed reflecting changes in distance traveled of the basal locomotor activity and thigmotaxis at the sampling points. In conclusion, pollutants in water from Villa Victoria dam caused oxidative damage, changes in SOD, CAT, GPx and AChE activity as well as embryotoxicity and modifications in the behavior of C. carpio larvae. This study demonstrates the need to implement restoration programs for this reservoir since, contamination in the Villa Victoria dam could eventually endanger aquatic life and human health.


Assuntos
Acetilcolinesterase , Carpas , Embrião não Mamífero , Larva , Estresse Oxidativo , Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo/efeitos dos fármacos , México , Acetilcolinesterase/metabolismo , Carpas/embriologia , Carpas/metabolismo , Larva/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos
2.
Ecotoxicol Environ Saf ; 270: 115888, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38150752

RESUMO

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


Assuntos
Glifosato , Herbicidas , Humanos , Animais , Peixe-Zebra/metabolismo , Glicina/toxicidade , Disbiose/induzido quimicamente , Ácido Chiquímico/metabolismo , Herbicidas/toxicidade , Neurotransmissores
3.
Int J Mol Sci ; 25(14)2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39062930

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and interest restricted to specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 h post-fertilization, rearing them to the adult stage in fish water. For the first time, an integrative approach combining behavioral analysis and neurotransmitters profile has been used for determining the effects of early-life exposure to VPA both in the larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. A neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the potential predictive validity of this model for ASD research.


Assuntos
Comportamento Animal , Modelos Animais de Doenças , Ácido Valproico , Peixe-Zebra , Animais , Ácido Valproico/toxicidade , Ácido Valproico/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Neurotransmissores/metabolismo , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/etiologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Larva/efeitos dos fármacos , Comportamento Social , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/crescimento & desenvolvimento
4.
Int J Mol Sci ; 24(18)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37762171

RESUMO

The increasing number of new psychoactive substances (NPS) entering the illicit drug market, especially synthetic cathinones, as well as the risk of cardiovascular complications, is intensifying the need to quickly assess their cardiotoxic potential. The present study aims to evaluate the cardiovascular toxicity and lethality induced by first-generation synthetic cathinones (mephedrone, methylone, and MDPV) and more classical psychostimulants (cocaine and MDMA) in zebrafish embryos using a new approach methodology (NAM). Zebrafish embryos at 4 dpf were exposed to the test drugs for 24 h to identify drug lethality. Drug-induced effects on ventricular and atrial heart rate after 2 h exposure were evaluated, and video recordings were properly analyzed. All illicit drugs displayed similar 24 h LC50 values. Our results indicate that all drugs are able to induce bradycardia, arrhythmia, and atrial-ventricular block (AV block), signs of QT interval prolongation. However, only MDPV induced a different rhythmicity change depending on the chamber and was the most potent bradycardia and AV block-inducing drug compared to the other tested compounds. In summary, our results strongly suggest that the NAM presented in this study can be used for screening NPS for their cardiotoxic effect and especially for their ability to prolong the QT intervals.


Assuntos
Fibrilação Atrial , Bloqueio Atrioventricular , Estimulantes do Sistema Nervoso Central , Drogas Ilícitas , Animais , Peixe-Zebra , Catinona Sintética , Bradicardia , Cardiotoxicidade/etiologia
5.
Angew Chem Int Ed Engl ; 61(30): e202203449, 2022 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-35608051

RESUMO

Catecholamine-triggered ß-adrenoceptor (ß-AR) signaling is essential for the correct functioning of the heart. Although both ß1 - and ß2 -AR subtypes are expressed in cardiomyocytes, drugs selectively targeting ß1 -AR have proven this receptor as the main target for the therapeutic effects of beta blockers in the heart. Here, we report a new strategy for the light-control of ß1 -AR activation by means of photoswitchable drugs with a high level of ß1 -/ß2 -AR selectivity. All reported molecules allow for an efficient real-time optical control of receptor function in vitro. Moreover, using confocal microscopy we demonstrate that the binding of our best hit, pAzo-2, can be reversibly photocontrolled. Strikingly, pAzo-2 also enables a dynamic cardiac rhythm management on living zebrafish larvae using light, thus highlighting the therapeutic and research potential of the developed photoswitches. Overall, this work provides the first proof of precise control of the therapeutic target ß1 -AR in native environments using light.


Assuntos
Receptores Adrenérgicos beta 2 , Peixe-Zebra , Antagonistas Adrenérgicos beta/farmacologia , Animais , Ligantes , Miócitos Cardíacos/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Peixe-Zebra/metabolismo
6.
Anal Bioanal Chem ; 412(23): 5695-5706, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32617759

RESUMO

Metabolomics is currently an important field within bioanalytical science and NMR has become a key technique for drawing the full metabolic picture. However, the analysis of 1H NMR spectra of metabolomics samples is often very challenging, as resonances usually overlap in crowded regions, hindering the steps of metabolite profiling and resonance integration. In this context, a pre-processing method for the analysis of 1D 1H NMR data from metabolomics samples is proposed, consisting of the blind resolution and integration of all resonances of the spectral dataset by multivariate curve resolution-alternating least squares (MCR-ALS). The resulting concentration estimates can then be examined with traditional chemometric methods such as principal component analysis (PCA), ANOVA-simultaneous component analysis (ASCA), and partial least squares-discriminant analysis (PLS-DA). Since MCR-ALS does not require the use of spectral templates, the concentration estimates for all resonances are obtained even before being assigned. Consequently, the metabolomics study can be performed without neglecting any relevant resonance. In this work, the proposed pipeline performance was validated with 1D 1H NMR spectra from a metabolomics study of zebrafish upon acrylamide (ACR) exposure. Remarkably, this method represents a framework for the high-throughput analysis of NMR metabolomics data that opens the way for truly untargeted NMR metabolomics analyses. Graphical abstract.


Assuntos
Acrilamida/toxicidade , Espectroscopia de Prótons por Ressonância Magnética/métodos , Animais , Análise Discriminante , Metabolômica , Análise Multivariada , Análise de Componente Principal , Peixe-Zebra
7.
Anal Bioanal Chem ; 410(6): 1735-1748, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29313079

RESUMO

There is a growing interest in biological models to investigate the effect of neurotransmitter dysregulation on the structure and function of the central nervous system (CNS) at different stages of development. Zebrafish, a vertebrate model increasingly used in neurobiology and neurotoxicology, shares the common neurotransmitter systems with mammals, including glutamate, GABA, glycine, dopamine, norepinephrine, epinephrine, serotonin, acetylcholine, and histamine. In this study, we have evaluated the performance of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the multiresidue determination of neurotransmitters and related metabolites. In a first step, ionization conditions were tested in positive electrospray mode and optimum fragmentation patterns were determined to optimize two selected reaction monitoring (SRM) transitions. Chromatographic conditions were optimized considering the chemical structure and chromatographic behavior of the analyzed compounds. The best performance was obtained with a Synergy Polar-RP column, which allowed the separation of the 38 compounds in 30 min. In addition, the performance of LC-MS/MS was studied in terms of linearity, sensitivity, intra- and inter-day precision, and overall robustness. The developed analytical method was able to quantify 27 of these neurochemicals in zebrafish chemical models for mild (P1), moderate (P2), and severe (P3) acute organophosphorus poisoning (OPP). The results show a general depression of synaptic-related neurochemicals, including the excitatory and inhibitory amino acids, as well as altered phospholipid metabolism, with specific neurochemical profiles associated to the different grades of severity. These results confirmed that the developed analytical method is a new tool for neurotoxicology research using the zebrafish model.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Intoxicação por Organofosfatos/diagnóstico , Espectrometria de Massas em Tandem/métodos , Peixe-Zebra , Acetilcolina/análise , Acetilcolina/metabolismo , Animais , Modelos Animais de Doenças , Dopamina/análise , Dopamina/metabolismo , Epinefrina/análise , Epinefrina/metabolismo , Ácido Glutâmico/análise , Ácido Glutâmico/metabolismo , Glicina/análise , Glicina/metabolismo , Histamina/análise , Histamina/metabolismo , Humanos , Neurotransmissores/análise , Neurotransmissores/metabolismo , Norepinefrina/análise , Norepinefrina/metabolismo , Intoxicação por Organofosfatos/metabolismo , Serotonina/análise , Serotonina/metabolismo , Peixe-Zebra/metabolismo , Ácido gama-Aminobutírico/análise , Ácido gama-Aminobutírico/metabolismo
8.
Ecotoxicol Environ Saf ; 164: 388-397, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30142605

RESUMO

Acute exposure to nicotinic agonists induces myotoxicity in zebrafish embryos. The main goal of this work was to evaluate the potential myotoxicity of nicotine acetylcholine receptor agonists on adult zebrafish muscle tissue by using nicotine as a model compound. Liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) datasets were processed with different chemometric tools based on the selection of Regions of Interest (ROI) and Multivariate Curve-Resolution (ROI-MCR procedure) Alternating Least Squares (ALS) for the analysis of different exposure experiments. Analysis of Variance Simultaneous Component Analysis (ASCA) of changes on metabolite peak profile areas showed significant nicotine concentration and exposure time-dependent changes, clearly differentiating between exposed and non-exposed samples and between short (2 h) and long exposure times (6 h or 24 h). Most of the changes observed in the concentrations of different metabolites are probably secondary to the observed hyperlocomotion, as they have been also observed in humans after strenuous muscular exercise. The absence of myotoxicity might be related with the reduced calcium permeability of adult muscle-type nicotinic acetylcholine receptors (nAChRs).


Assuntos
Metabolômica , Músculo Esquelético/efeitos dos fármacos , Nicotina/toxicidade , Peixe-Zebra/metabolismo , Acetilcarnitina/metabolismo , Animais , Cálcio/metabolismo , Carnitina/metabolismo , Cromatografia Líquida , Relação Dose-Resposta a Droga , Masculino , Modelos Animais , Músculo Esquelético/metabolismo , Serotonina/metabolismo , Testes de Toxicidade Aguda
9.
Neurobiol Dis ; 98: 36-51, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27890673

RESUMO

ABHD12 mutations have been linked to neurodegenerative PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract), a rare, progressive, autosomal, recessive disease. Although ABHD12 is suspected to play a role in the lysophosphatidylserine and/or endocannabinoid pathways, its precise functional role(s) leading to PHARC disease had not previously been characterized. Cell and zebrafish models were designed to demonstrate the causal link between an identified new missense mutation p.T253R, characterized in ABHD12 from a young patient, the previously characterized p.T202I and p.R352* mutations, and the associated PHARC. Measuring ABHD12 monoacylglycerol lipase activity in transfected HEK293 cells demonstrated inhibition with mutated isoforms. Both the expression pattern of zebrafish abhd12 and the phenotype of specific antisense morpholino oligonucleotide gene knockdown morphants were consistent with human PHARC hallmarks. High abhd12 transcript levels were found in the optic tectum and tract, colocalized with myelin basic protein, and in the spinal cord. Morphants have myelination defects and concomitant functional deficits, characterized by progressive ataxia and motor skill impairment. A disruption of retina architecture and retinotectal projections was observed, together with an inhibition of lens clarification and a low number of mechanosensory hair cells in the inner ear and lateral line system. The severe phenotypes in abhd12 knockdown morphants were rescued by introducing wild-type human ABHD12 mRNA, but not by mutation-harboring mRNAs. Zebrafish may provide a suitable vertebrate model for ABHD12 insufficiency and the study of functional impairment and potential therapeutic rescue of this rare, neurodegenerative disease.


Assuntos
Ataxia/genética , Catarata/genética , Monoacilglicerol Lipases/genética , Mutação de Sentido Incorreto , Polineuropatias/genética , Retinose Pigmentar/genética , Adulto , Animais , Animais Geneticamente Modificados , Ataxia/patologia , Ataxia/fisiopatologia , Catarata/patologia , Catarata/fisiopatologia , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Modelos Animais , Monoacilglicerol Lipases/metabolismo , Bainha de Mielina/metabolismo , Bainha de Mielina/patologia , Fenótipo , Polineuropatias/patologia , Polineuropatias/fisiopatologia , RNA Mensageiro/metabolismo , Retinose Pigmentar/patologia , Retinose Pigmentar/fisiopatologia , Sensação/fisiologia , Natação/fisiologia , Peixe-Zebra
10.
Arch Toxicol ; 91(4): 1891-1901, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27655295

RESUMO

Acute organophosphorus (OP) intoxication is a worldwide clinical and public health problem. In addition to cholinergic crisis, neurodegeneration and brain damage are hallmarks of the severe form of this toxidrome. Recently, we generated a chemical model of severe acute OP intoxication in zebrafish that is characterized by altered head morphology and brain degeneration. The pathophysiological pathways resulting in brain toxicity in this model are similar to those described in humans. The aim of this study was to assess the predictive power of this zebrafish model by testing the effect of a panel of drugs that provide protection in mammalian models. The selected drugs included "standard therapy" drugs (atropine and pralidoxime), reversible acetylcholinesterase inhibitors (huperzine A, galantamine, physostigmine and pyridostigmine), N-methyl-D-aspartate (NMDA) receptor antagonists (MK-801 and memantine), dual-function NMDA receptor and acetylcholine receptor antagonists (caramiphen and benactyzine) and anti-inflammatory drugs (dexamethasone and ibuprofen). The effects of these drugs on zebrafish survival and the prevalence of abnormal head morphology in the larvae exposed to 4 µM chlorpyrifos oxon [1 × median lethal concentration (LC50)] were determined. Moreover, the neuroprotective effects of pralidoxime, memantine, caramiphen and dexamethasone at the gross morphological level were confirmed by histopathological and transcriptional analyses. Our results demonstrated that the zebrafish model for severe acute OP intoxication has a high predictive value and can be used to identify new compounds that provide neuroprotection against severe acute OP intoxication.


Assuntos
Encéfalo/efeitos dos fármacos , Clorpirifos/análogos & derivados , Fármacos Neuroprotetores/farmacologia , Intoxicação por Organofosfatos/tratamento farmacológico , Animais , Antídotos/farmacologia , Encéfalo/fisiopatologia , Clorpirifos/administração & dosagem , Clorpirifos/toxicidade , Modelos Animais de Doenças , Dose Letal Mediana , Intoxicação por Organofosfatos/fisiopatologia , Peixe-Zebra
11.
Ecotoxicol Environ Saf ; 145: 583-590, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28802139

RESUMO

Incorporation of chemometric tools in behavioural data management workflows allows for the early identification of most relevant endpoints complementarily to statistical confirmatory approaches. In this work, the effects of two model neurotoxicants, chlorpyrifos (CPF) and nicotine, exposures on behavioural profiles of adult zebrafish at three different times (2, 6 and 24h) were evaluated using open field test (OFT) paradigm experiments. Two chemometric methods like Principal Component Analysis (PCA) and Analysis of Variance-Simultaneous Component Analysis (ASCA) have been used to interpret the changes observed in the obtained behavioural data. A decreased of the locomotor activity, an anxiolytic effect and an altered exploratory behaviour were the most affected behavioural endpoints in the CPF exposures. However, an increase of the locomotor activity and an anxiogenic effect were observed in the nicotine exposures. Finally, an excellent correlation between the ASCA results and the results obtained using traditional statistical procedures for both compounds were encountered.


Assuntos
Comportamento Animal/efeitos dos fármacos , Ecotoxicologia/métodos , Poluentes Ambientais/toxicidade , Atividade Motora/efeitos dos fármacos , Peixe-Zebra/metabolismo , Análise de Variância , Animais , Clorpirifos/metabolismo , Clorpirifos/toxicidade , Ecotoxicologia/estatística & dados numéricos , Poluentes Ambientais/metabolismo , Nicotina/metabolismo , Nicotina/toxicidade , Análise de Componente Principal
12.
Bull Environ Contam Toxicol ; 96(6): 707-13, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27086301

RESUMO

Zebrafish models for mild, moderate, and severe acute organophosphorus poisoning were previously developed by exposing zebrafish larvae to chlopyrifos-oxon. The phenotype of these models was characterized at several levels of biological organization. Oxidative stress and mitochondrial dysfunction were found to be involved in the development of the more severe phenotype. Here we used targeted gene expression to understand the dose-responsiveness of those two pathways and their involvement on generating the different zebrafish models. As the severe phenotype is irreversible after only 3 h of exposure, we also analyzed the response of the oxidative stress pathway at 3 and 24 h. Some of the genes related to oxidative stress were already differentially expressed at 3 h. There was an increase in differentially expressed genes related to both oxidative stress and mitochondrial function from the more mild to the more severe phenotype, suggesting the involvement of these mechanisms in increasing phenotype severity. Temporal data suggest that peroxynitrite leading to lipid peroxidation might be involved in phenotype transition and irreversibility.


Assuntos
Clorpirifos/análogos & derivados , Expressão Gênica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Clorpirifos/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Fenótipo , Peixe-Zebra/metabolismo
13.
Toxics ; 12(8)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39195640

RESUMO

Last year (2023) was the tenth anniversary of Toxics [...].

14.
Sci Total Environ ; 917: 170463, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38290680

RESUMO

Aquatic organisms are exposed to low concentrations of neuro-active chemicals, many of them acting also as neuroendocrine disruptors that can be hazardous during earlier embryonic stages. The present study aims to assess how exposure early in live to environmental low concentrations of two selective serotonin reuptake inhibitors (SSRIs), fluoxetine and sertraline, and tributyltin (TBT) affected cognitive, metabolic and cardiac responses in the model aquatic crustacean Daphnia magna. To that end, newly brooded females were exposed for an entire reproductive cycle (3-4 days) and the response of collected juveniles in the first, second and third consecutive broods, which were exposed, respectively, as embryos, provisioned and un-provisioned egg stages, was monitored. Pre-exposure to the selected SSRIs during embryonic and egg developmental stages altered the swimming behaviour of D. magna juveniles to light in a similar way reported elsewhere by serotonergic compounds while TBT altered cognition disrupting multiple neurological signalling routes. The studied compounds also altered body size, the amount of storage lipids in lipid droplets, heart rate, oxygen consumption rates and the transcription of related serotonergic, dopaminergic and lipid metabolic genes in new-born individuals, mostly pre-exposed during their embryonic and provisioning egg stages. The obtained cognitive, cardiac and metabolic defects in juveniles developed from exposed sensitive pre-natal stages align with the "Developmental Origins of Health and Disease (DoHAD)" paradigm.


Assuntos
Inibidores Seletivos de Recaptação de Serotonina , Compostos de Trialquitina , Poluentes Químicos da Água , Animais , Feminino , Humanos , Inibidores Seletivos de Recaptação de Serotonina/toxicidade , Daphnia magna , Serotonina/metabolismo , Exposição Materna , Daphnia/fisiologia , Cognição , Poluentes Químicos da Água/análise
15.
MethodsX ; 12: 102492, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38089153

RESUMO

Zebrafish larvae are a model organism increasingly used in the study of the effect of neuroactive chemicals on vertebrate sleep/wake cycles. Sleep disturbances have a negative impact on mood, cognition and overall health. Here we present a protocol to assess over 24 h sleep/wake cycles in zebrafish larvae subjected to 12 h light/dark periods in 48-well plates, using video-tracking technologies. The protocol can be used to determine if the exposure to environmental pollutants or drugs can lead to sleep disturbances. The results on the effect of the tire rubber-derived 6PPD-quinone on zebrafish sleep/wake cycles presented here demonstrate the suitability of using this protocol in fish neurotoxicity studies. This protocol provides a new relevant tool to be used in the pharmacology and toxicology fields.

16.
Sci Total Environ ; 953: 175984, 2024 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-39244042

RESUMO

Alkyldimethylbenzylammonium chlorides (ADBACs), classified as second-generation quaternary ammonium compounds, are extensively employed across various sectors, encompassing veterinary medicine, food production, pharmaceuticals, cosmetics, ophthalmology, and agriculture. Consequently, significant volumes of ADBAC C12-C16 are discharged into the environment, posing a threat to aquatic organisms. Regrettably, comprehensive data regarding the toxicological characteristics of these compounds remain scarce. This research aimed to determine whether or not ADBAC C12-C16, at environmentally relevant concentrations (0.4, 0.8, and 1.6 µg/L), may instigate oxidative stress and alter the expression of apoptosis-related genes in the liver, brain, gut, and gills of Danio rerio adults (5-6 months). The findings revealed that ADBAC C12-C16 elicited an oxidative stress response across all examined organs following 96 h of exposure. Nonetheless, the magnitude of this response varied among organs, with the gills exhibiting the highest degree of susceptibility, followed by the gut, liver, and brain, in descending order. Only the gut and gills of the examined organs displayed a concentration-dependent reduction in the activity of superoxide dismutase (SOD) and catalase (CAT). Akin to the oxidative stress response, all organs exhibited a marked increase in bax, blc2, casp3, and p53 expression levels. However, the gills and gut manifested a distinctive suppression in the expression of nrf1 and nrf2. Our Principal Component Analysis (PCA) confirmed that SOD, CAT, nrf1, and nrf2 were negatively correlated to oxidative damage biomarkers and apoptosis-related genes in the gills and gut; meanwhile, in the remaining organs, all biomarkers were extensively correlated. From the above, it can be concluded that ADBAC C12-C16 in low and environmental concentrations may threaten the health of freshwater fish.


Assuntos
Estresse Oxidativo , Poluentes Químicos da Água , Peixe-Zebra , Animais , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Compostos de Benzalcônio/toxicidade
17.
Aquat Toxicol ; 276: 107088, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39265222

RESUMO

Global warming due to climate change, as well as freshwater eutrophication caused by anthropogenic activities are responsible, among other factors, for an increasing occurrence of harmful algal blooms (HABs) in aquatic systems. These can lead to the generation of cyanotoxins, secondary metabolites coming from cyanobacteria, producing adverse effects in living organisms including death. This research aims to study the effects that two neurotoxins, anatoxin-a (ATX-a) and saxitoxin (STX), have on living organisms. Once the stability of both compounds in water was determined for a 24 h period using ultra-high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer (UPLC-MS/MS), zebrafish larvae were exposed to different levels of toxins (1 ng L-1, 10 ng L-1, 100 ng L-1 and 1 µg L-1) during 24 h. Behavioral studies including vibrational startle response (VSR), habituation to vibrational stimuli, basal locomotor activity (BLM) and visual motor response (VMR) were performed using Danio Vision system, and neurotransmitters (NTs) from 15-head pools of control and exposed zebrafish larvae were extracted and analyzed by UPLC-MS/MS. Both compounds induced hypolocomotion in the individuals, while 10 and 100 ng L-1 of ATX-a significantly increased methionine (120 % and 126 %, respectively) and glutamate levels (118 % and 129 %, respectively). Saxitoxin enhanced 3-metoxytyramine (3-MT) levels at 1 ng L-1 by 185 %. The findings of this study show that both studied cyanotoxins influence the behavior of zebrafish larvae as well as their metabolism.

18.
Environ Pollut ; 347: 123685, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38460591

RESUMO

Boscalid (2-Chloro-N-(4'-chlorobiphenyl-2-yl) nicotinamide), a pyridine carboxamide fungicide, is an inhibitor of the complex II of the respiration chain in fungal mitochondria. As boscalid is only moderately toxic for aquatic organisms (LC50 > 1-10 mg/L), current environmental levels of this compound in aquatic ecosystems, in the range of ng/L-µg/L, are considered safe for aquatic organisms. In this study, we have exposed zebrafish (Danio rerio), Japanese medaka (Oryzias latipes) and Daphnia magna to a range of concentrations of boscalid (1-1000 µg/L) for 24 h, and the effects on heart rate (HR), basal locomotor activity (BLA), visual motor response (VMR), startle response (SR), and habituation (HB) to a series of vibrational or light stimuli have been evaluated. Moreover, changes in the profile of the main neurotransmitters have been determined. Boscalid altered HR in a concentration-dependent manner, leading to a positive or negative chronotropic effect in fish and D. magna, respectively. While boscalid decreased BLA and increased VMR in Daphnia, these behaviors were not altered in fish. For SR and HB, the response was more species- and concentration-specific, with Daphnia exhibiting the highest sensitivity. At the neurotransmission level, boscalid exposure decreased the levels of L-aspartic acid in fish larvae and increased the levels of dopaminergic metabolites in D. magna. Our study demonstrates that exposure to environmental levels of boscalid alters cardiac activity, impairs ecologically relevant behaviors, and leads to changes in different neurotransmitter systems in phylogenetically distinct vertebrate and invertebrate models. Thus, the results presented emphasize the need to review the current regulation of this fungicide.


Assuntos
Compostos de Bifenilo , Fungicidas Industriais , Niacinamida/análogos & derivados , Poluentes Químicos da Água , Animais , Fungicidas Industriais/metabolismo , Ecossistema , Organismos Aquáticos , Peixe-Zebra/metabolismo , Daphnia , Niacinamida/toxicidade , Poluentes Químicos da Água/metabolismo
19.
Sci Total Environ ; 912: 169301, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38103609

RESUMO

The current view is that environmental levels of nicotine and cotinine, commonly in the ng/L range, are safe for aquatic organisms. In this study, 7 days post-fertilization zebrafish embryos have been exposed for 24 h to a range of environmental concentrations of nicotine (2.0 ng/L-2.5 µg/L) and cotinine (50 pg/L-10 µg/L), as well as to a binary mixture of these emerging pollutants. Nicotine exposure led to hyperactivity, decreased vibrational startle response and increased non-associative learning. However, the more consistent effect found for both nicotine and cotinine was a significant increase in light-off visual motor response (VMR). The effect of both pollutants on this behavior occurred through a similar mode of action, as the joint effects of the binary mixture of both chemicals were consistent with the concentration addition concept predictions. The results from docking studies suggest that the effect of nicotine and cotinine on light-off VMR could be mediated by zebrafish α7 nAChR expressed in retina. The results presented in this study emphasize the need to revisit the environmental risk assessment of chemicals including additional ecologically relevant sublethal endpoints.


Assuntos
Poluentes Ambientais , Nicotina , Animais , Nicotina/toxicidade , Cotinina , Peixe-Zebra , Larva
20.
Toxics ; 12(5)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38787128

RESUMO

The recent availability of commercial platforms for behavioral analyses in zebrafish larvae based on video-tracking technologies has exponentially increased the number of studies analyzing different behaviors in this model organism to assess neurotoxicity. Among the most commonly used assays in zebrafish larvae are basal locomotor activity (BLA) and visual motor responses (VMRs). However, the effect of different intrinsic and extrinsic factors that can significantly alter the outcome of these assays is still not well understood. In this work, we have analyzed the influence of age (5-8 days post-fertilization), time of day (8:00, 10:00, 12:00, 14:00; 16:00, 18:00, and 20:00 h), and experiment (three experiments performed at different days) on BLA and VMR results (4004 analyses for each behavior) in 143 larvae. The results from both behaviors were adjusted to a random-effects linear regression model using generalized least squares (GLSs), including in the model the effect of the three variables, the second-way interactions between them, and the three-way interaction. The results presented in this manuscript show a specific effect of all three intrinsic factors and their interactions on both behaviors, supporting the view that the most stable time period for performing these behavioral assays is from 10:00 am to 04:00 pm, with some differences depending on the age of the larva and the behavioral test.

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