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1.
Part Fibre Toxicol ; 19(1): 26, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35392949

RESUMO

BACKGROUND: Nanomaterials have been widely used in electrochemistry, sensors, medicine among others applications, causing its inevitable environmental exposure. A raising question is the "carrier" effect due to unique surface properties of nanomaterials, which may collectively impact the bioavailability, toxicokinetic, distribution and biological effects of classic toxicants. Noteworthy, this aspect of information remains largely unexplored. METHODS: Here, we deliberately selected two entities to mimic this scenario. One is graphene oxide (GO), which is made in ton quantity with huge surface-area that provides hydrophilicity and π-π interaction to certain chemicals of unique structures. The other is Microcystin-LR (MCLR), a representative double-bond rich liver-toxic endotoxin widely distributed in aquatic-system. Firstly, the adsorption of GO and MCLR after meeting under environmental conditions was explored, and then we focused on the toxicological effect and related mechanism of GO-MCLR complex on human skin cutin forming cells (HaCaT cells) and normal liver cells (L02 cells). RESULTS: Abiotically, our study demonstrated that GO could effectively adsorb MCLR through hydrogen bonding and π-π interaction, the oxidation degree of GO-MCLR decreased significantly and surface defect level raised. Compared to GO or MCLR, GO-MCLR was found to induce more remarkable apoptosis and ferroptosis in both HaCaT and L02 cells. The underlying mechanism was that GO-MCLR induced stronger intracellular reactive oxygen species (ROS) and mtROS generation, followed by Fe2+ accumulation, mitochondrial dysfunction and cytoskeletal damage. CONCLUSIONS: These results suggest that the GO-MCLR complex formed by GO adsorption of MCLR may exhibit more toxic effects than the single material, which demonstrates the necessity for assessing nano-toxicant complexity. Our discovery may serve as a new toxicological paradigm in which nanomaterial mediated surface adsorption effects could impact the degree of cytotoxicity and toxicological mechanisms of classic toxins.


Assuntos
Grafite , Microcistinas , Grafite/toxicidade , Humanos , Toxinas Marinhas/toxicidade , Microcistinas/química , Microcistinas/toxicidade
2.
Toxicology ; 470: 153157, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35307467

RESUMO

Domoic acid (DA) is a marine neurotoxin produced as a defence compound by diatom Pseudo-nitzschia. Although its toxicity is well known in marine mammals and fish, data on DA cyto/genotoxicity in human non-target cells is still limited. Hence, we aimed to study the effect of DA (0.001-10 µg/mL) on cell viability and proliferation kinetics of human hepatocellular carcinoma (HepG2) cells as well as DNA damage induction after 4, 24 and 72 h of exposure. The results revealed that DA up to 10 µg/mL did not elicit significant changes in HepG2 cell viability, proliferation and cell cycle at applied conditions. DA did not generate DNA double-strand breaks, while it exhibited significant dose- and time-dependent increase of DNA damage in the form of either DNA single-strand breaks or alkali labile sites. Additionally, increased malondialdehyde level after DA treatment indicated oxidative damage to lipids. Altogether, the results showed that neurotoxin DA induced only minor adverse genotoxic effects in non-target HepG2 cells that most probably occurred resulting from the oxidative stress. However, additional research is needed to further elucidate the mechanisms of DA toxicity, particularly in terms of chronic exposure, as well as to understand its potential influence on human non-target cells.


Assuntos
Diatomáceas , Neurotoxinas , Animais , DNA/metabolismo , Diatomáceas/metabolismo , Células Hep G2 , Humanos , Ácido Caínico/análogos & derivados , Ácido Caínico/toxicidade , Mamíferos , Toxinas Marinhas/metabolismo , Toxinas Marinhas/toxicidade , Neurotoxinas/toxicidade
3.
Mar Drugs ; 20(3)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35323498

RESUMO

Harmful algal blooms pose a challenge regarding food safety due to their erratic nature and forming circumstances which are yet to be disclosed. The best strategy to protect human consumers is through legislation and monitoring strategies. Global warming and anthropological intervention aided the migration and establishment of emerging toxin producers into Europe's temperate waters, creating a new threat to human public health. The lack of information, standards, and reference materials delay effective solutions, being a matter of urgent resolution. In this work, the recent findings of the presence of emerging azaspiracids, spirolildes, pinnatoxins, gymnodimines, palitoxins, ciguatoxins, brevetoxins, and tetrodotoxins on European Coasts are addressed. The information concerning emerging toxins such as new matrices, locations, and toxicity assays is paramount to set the risk assessment guidelines, regulatory levels, and analytical methodology that would protect the consumers.


Assuntos
Toxinas Marinhas/análise , Toxinas Marinhas/toxicidade , Poluentes da Água/análise , Poluentes da Água/toxicidade , Animais , Monitoramento Ambiental , Europa (Continente) , Humanos , Medição de Risco
4.
Mar Drugs ; 20(3)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35323497

RESUMO

Marine phycotoxins are a multiplicity of bioactive compounds which are produced by microalgae and bioaccumulate in the marine food web. Phycotoxins affect the ecosystem, pose a threat to human health, and have important economic effects on aquaculture and tourism worldwide. However, human health and food safety have been the primary concerns when considering the impacts of phycotoxins. Phycotoxins toxicity information, often used to set regulatory limits for these toxins in shellfish, lacks traceability of toxicity values highlighting the need for predefined toxicological criteria. Toxicity data together with adequate detection methods for monitoring procedures are crucial to protect human health. However, despite technological advances, there are still methodological uncertainties and high demand for universal phycotoxin detectors. This review focuses on these topics, including uncertainties of climate change, providing an overview of the current information as well as future perspectives.


Assuntos
Toxinas Marinhas , Microalgas , Poluentes da Água , Animais , Mudança Climática , Humanos , Toxinas Marinhas/análise , Toxinas Marinhas/uso terapêutico , Toxinas Marinhas/toxicidade , Poluentes da Água/análise , Poluentes da Água/uso terapêutico , Poluentes da Água/toxicidade
5.
Aquat Toxicol ; 245: 106127, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35248895

RESUMO

Computational molecular modelling, mass spectrometry and in-vivo tests with Chlorella vulgaris (C. vulgaris) and Daphnia magna (D. magna) were used to investigate the liposolubility and ecotoxicity of MC-LR degradation by-products generated after oxidation by OH• radicals in Fenton process. Exposure of MC-LR (5 µg.L-1) to the most severe oxidation conditions (Fe2+ 20 mM and H2O2 60 mM) resulted in a reduction in the toxin concentration of 96% (0.16 µg.L-1), however, with the formation of many by-products. The by-product of m/z 445 was the most resistant to degradation and retained a toxic structure of diene bonds present in the Adda amino acid. Computational modeling revealed that m/z 445 (tPSA = 132.88 Ų; KOW = 2.02) is more fat-soluble than MC-LR (tPSA = 340.64 Ų; KOW = 0.68), evidencing an easier transport process of this by-product. Given this, toxicity tests using C. vulgaris and D. magna indicated greater toxicity of the by-product m/z 445 compared to MC-LR. When the conversion of MC-LR to by-products was 77%, the growth inhibition of C. vulgaris and the D. magna immobility were, respectively, 6.14 and 0%, with 96% conversion; growth inhibition and the immobility were both 100%  for both species.


Assuntos
Chlorella vulgaris , Poluentes Químicos da Água , Animais , Simulação por Computador , Daphnia/metabolismo , Peróxido de Hidrogênio/metabolismo , Toxinas Marinhas/toxicidade , Microcistinas/toxicidade , Poluentes Químicos da Água/toxicidade
6.
Mar Drugs ; 20(2)2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35200651

RESUMO

A variety of microalgal species produce lipophilic toxins (LT) that are accumulated by filter-feeding bivalves. Their negative impacts on human health and shellfish exploitation are determined by toxic potential of the local strains and toxin biotransformations by exploited bivalve species. Chile has become, in a decade, the world's major exporter of mussels (Mytilus chilensis) and scallops (Argopecten purpuratus) and has implemented toxin testing according to importing countries' demands. Species of the Dinophysis acuminata complex and Protoceratium reticulatum are the most widespread and abundant LT producers in Chile. Dominant D. acuminata strains, notwithstanding, unlike most strains in Europe rich in okadaic acid (OA), produce only pectenotoxins, with no impact on human health. Dinophysis acuta, suspected to be the main cause of diarrhetic shellfish poisoning outbreaks, is found in the two southernmost regions of Chile, and has apparently shifted poleward. Mouse bioassay (MBA) is the official method to control shellfish safety for the national market. Positive results from mouse tests to mixtures of toxins and other compounds only toxic by intraperitoneal injection, including already deregulated toxins (PTXs), force unnecessary harvesting bans, and hinder progress in the identification of emerging toxins. Here, 50 years of LST events in Chile, and current knowledge of their sources, accumulation and effects, are reviewed. Improvements of monitoring practices are suggested, and strategies to face new challenges and answer the main questions are proposed.


Assuntos
Toxinas Marinhas/toxicidade , Microalgas/metabolismo , Intoxicação por Frutos do Mar/prevenção & controle , Animais , Bioensaio/métodos , Bivalves/química , Bivalves/metabolismo , Chile , Humanos , Toxinas Marinhas/isolamento & purificação , Camundongos
7.
Toxicon ; 210: 78-88, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35150660

RESUMO

Microcystin-LR (MC-LR) has been identified to pose an increasing threat to the male reproductive system in vivo and in vitro studies with the objects like mammal animals, amphibians, aquatic organisms, etc. This review demonstrates the latest research advances of the male reproductive toxicity induced by MC-LR in detail, which mainly consists of two aspects, namely pathological injuries to testis and prostate, as well as the endocrine disruption. Apart from the direct toxicity to the male reproductive system, we also underline the transgenerational reproductive toxicity that prenatal exposure may pass on to male offspring. This review also demonstrates the interactive effects between MC-LR and other compounds, including synergistic effects with some toxicants and antagonistic effects with some medicine or chemical modification. In terms of the mechanisms of MC-LR-induced toxicity, we mainly focus on the epigenetic modification and non-coding RNAs (ncRNAs)-related mechanisms which have provided a new perspective.


Assuntos
Arginina , Microcistinas , Animais , Arginina/toxicidade , Leucina/toxicidade , Masculino , Mamíferos , Toxinas Marinhas/toxicidade , Microcistinas/toxicidade
8.
Toxins (Basel) ; 14(2)2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-35202135

RESUMO

The cysteine aspartic acid-specific protease (caspase) family is distributed across vertebrates and invertebrates, and its members are involved in apoptosis and response to cellular stress. The Zhikong scallop (Chlamys farreri) is a bivalve mollusc that is well adapted to complex marine environments, yet the diversity of caspase homologues and their expression patterns in the Zhikong scallop remain largely unknown. Here, we identified 30 caspase homologues in the genome of the Zhikong scallop and analysed their expression dynamics during all developmental stages and following exposure to paralytic shellfish toxins (PSTs). The 30 caspase homologues were classified as initiators (caspases-2/9 and caspases-8/10) or executioners (caspases-3/6/7 and caspases-3/6/7-like) and displayed increased copy numbers compared to those in vertebrates. Almost all of the caspase-2/9 genes were highly expressed throughout all developmental stages from zygote to juvenile, and their expression in the digestive gland and kidney was slightly influenced by PSTs. The caspase-8/10 genes were highly expressed in the digestive gland and kidney, while PSTs inhibited their expression in these two organs. After exposure to different Alexandrium PST-producing algae (AM-1 and ACDH), the number of significantly up-regulated caspase homologues in the digestive gland increased with the toxicity level of PST derivatives, which might be due to the higher toxicity of GTXs produced by AM-1 compared to the N-sulphocarbamoyl analogues produced by ACDH. However, the effect of these two PST-producing algae strains on caspase expression in the kidney seemed to be stronger, possibly because the PST derivatives were transformed into highly toxic compounds in scallop kidney, and suggested an organ-dependent response to PSTs. These results indicate the dedicated control of caspase gene expression and highlight their contribution to PSTs in C. farreri. This work provides a further understanding of the role of caspase homologues in the Zhikong scallop and can guide future studies focussing on the role of caspases and their interactions with PSTs.


Assuntos
Caspases/genética , Dinoflagelados , Toxinas Marinhas/toxicidade , Pectinidae/enzimologia , Animais , Trato Gastrointestinal/metabolismo , Rim/metabolismo , Pectinidae/genética , Filogenia
9.
Mar Drugs ; 20(2)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35200611

RESUMO

Palytoxin (PLTX) is a highly toxic polyether identified in various marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. In addition to adverse effects in humans, negative impacts on different marine organisms have been often described during Ostreopsis blooms and the concomitant presence of PLTX and its analogues. Considering the increasing frequency of Ostreopsis blooms due to global warming, PLTX was investigated for its effects on Artemia franciscana, a crustacean commonly used as a model organism for ecotoxicological studies. At concentrations comparable to those detected in culture media of O. cf. ovata (1.0-10.0 nM), PLTX significantly reduced cysts hatching and induced significant mortality of the organisms, both at larval and adult stages. Adults appeared to be the most sensitive developmental stage to PLTX: significant mortality was recorded after only 12 h of exposure to PLTX concentrations > 1.0 nM, with a 50% lethal concentration (LC50) of 2.3 nM (95% confidence interval = 1.2-4.7 nM). The toxic effects of PLTX toward A. franciscana adults seem to involve oxidative stress induction. Indeed, the toxin significantly increased ROS levels and altered the activity of the major antioxidant enzymes, in particular catalase and peroxidase, and marginally glutathione-S-transferase and superoxide dismutase. On the whole, these results indicate that environmentally relevant concentrations of PLTX could have a negative effect on Artemia franciscana population, suggesting its potential ecotoxicological impact at the marine level.


Assuntos
Acrilamidas/toxicidade , Artemia/efeitos dos fármacos , Venenos de Cnidários/toxicidade , Toxinas Marinhas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Acrilamidas/administração & dosagem , Animais , Venenos de Cnidários/administração & dosagem , Relação Dose-Resposta a Droga , Ecotoxicologia , Dose Letal Mediana , Estágios do Ciclo de Vida , Toxinas Marinhas/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
10.
Arch Toxicol ; 96(3): 831-843, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35037095

RESUMO

Okadaic acid (OA) is an important marine lipophilic phycotoxin with various pathological properties, responsible for diarrheal shellfish poisoning events in human beings over the world. However, to date no mechanism can well explain the toxicity and symptom of OA, even diarrhea. Here, to reveal the toxic mechanism of OA to mammals, we analyzed the metabolism of OA in rat and the effects of OA exposure on the composition and function of gut bacteria using a multi-omics strategy and rRNA high-throughput technology. We found that OA exerted great effects on gut bacteria, mainly featured in heavy fluctuation of dominant genera and significant changes in the mapped bacterial function genes, including not only virulence genes of pathogenic bacteria, but also bacterial metabolism genes. In the feces of the OA-exposed group, we detected dinophysistoxin-2 (DTX-2), lespedezaflavanone F and tolytoxin, suggesting that OA could be transformed into other metabolites like DTX-2. Other metabolic biomarkers such as N-Acetyl-a-neuraminic acid, N,N-dihydroxy-L-tyrosine, nalbuphine, and coproporphyrin I and III were also highly correlated with OA content, which made the toxicity of OA more complicated and confusing. Spearman correlation test demonstrated that Bacteroides and Romboutsia were the genera most related to OA transformation, suggesting that Bacteroides and Romboutsia might play a key role in the complicated and confusing toxicity of OA. In this study, we found for the first time that OA may be converted into other metabolites in gut, especially DTX-2. This finding could not only help to reveal the complex toxicity of OA, but also have important significance for clarifying the transportation, metabolism, and environmental fate of OA in the food chain.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Toxinas Marinhas/metabolismo , Ácido Okadáico/metabolismo , Animais , Bactérias/genética , Bactérias/metabolismo , Bactérias/patogenicidade , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Toxinas Marinhas/toxicidade , Metabolômica , Ácido Okadáico/toxicidade , Ratos , Ratos Wistar
11.
Toxins (Basel) ; 14(1)2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-35051037

RESUMO

Diatoms of the genus Pseudo-nitzschia H.Peragallo are known to produce domoic acid (DA), a toxin involved in amnesic shellfish poisoning (ASP). Strains of the same species are often classified as both toxic and nontoxic, and it is largely unknown whether this difference is also genetic. In the Northern Adriatic Sea, there are virtually no cases of ASP, but DA occasionally occurs in shellfish samples. So far, three species-P. delicatissima (Cleve) Heiden, P. multistriata (H. Takano) H. Takano, and P. calliantha Lundholm, Moestrup, & Hasle-have been identified as producers of DA in the Adriatic Sea. By means of enzme-linked immunosorbent assay (ELISA), high-performance liquid chromatography with UV and visible spectrum detection (HPLC-UV/VIS), and liquid chromatography with tandem mass spectrometry (LC-MS/MS), we reconfirmed the presence of DA in P. multistriata and P. delicatissima and detect for the first time in the Adriatic Sea DA in P. galaxiae Lundholm, & Moestrup. Furthermore, we attempted to answer the question of the distribution of DA production among Pseudo-nitzschia species and strains by sequencing the internal transcribed spacer (ITS) phylogenetic marker and the dabA DA biosynthesis gene and coupling this with toxicity data. Results show that all subclades of the Pseudo-nitzschia genus contain toxic species and that toxicity appears to be strain dependent, often with geographic partitioning. Amplification of dabA was successful only in toxic strains of P. multistriata and the presence of the genetic architecture for DA production in non-toxic strains was thus not confirmed.


Assuntos
Diatomáceas/química , Testes Genéticos , Ácido Caínico/análogos & derivados , Toxinas Marinhas/toxicidade , Água do Mar/parasitologia , Testes de Toxicidade , Cromatografia Líquida de Alta Pressão , Ensaio de Imunoadsorção Enzimática , Ácido Caínico/toxicidade , Espectrometria de Massas em Tandem
12.
Artigo em Inglês | MEDLINE | ID: mdl-34826614

RESUMO

With the intensification of water eutrophication around the world, cyanobacterial blooms have been becoming a common environmental pollution problem. The levels of microcystin-LR (MC-LR) and nitrite rise sharply during the cyanobacterial bloom period, which may have potential joint toxicity on aquatic organisms. In this study, adult male zebrafish were immersed into different joint solutions of MC-LR (0, 3, 30 µg/L) and nitrite (0, 2, 20 mg/L) for 30 days to explore the neurotoxic effects and underlying mechanisms. The results showed that single factor MC-LR or nitrite caused a concentration-dependent damage in brain ultrastructure and the effects of their joint exposure were much more intense. Downregulated expression of mbp and bdnf associated with myelination of nerve fibers further confirmed that MC-LR and nitrite could damage the structure and function of neuron. The decreases in dopamine content, acetylcholinesterase activity and related gene mRNA levels indicated that MC-LR and nitrite adversely affected the normal function of the dopaminergic and cholinergic systems in zebrafish brain. In addition, the significant increase in malondialdehyde content suggested the occurrence of oxidative stress caused by MC-LR, nitrite and their joint-exposure, which paralleled a significant decrease in antioxidant enzyme­manganese superoxide dismutase activity and its transcription level. In conclusion, MC-LR + Nitrite joint-exposure has synergistic neurotoxic effects on the structure and neurotransmitter systems of fish brain, and antioxidant capacity disruption caused by these two factors might be one of the underlying synergistic mechanisms. Therefore, there is a risk of being induced neurotoxicity in fish during sustained cyanobacterial bloom events.


Assuntos
Toxinas Marinhas/toxicidade , Microcistinas/toxicidade , Síndromes Neurotóxicas/etiologia , Neurotransmissores/metabolismo , Nitritos/toxicidade , Peixe-Zebra/fisiologia , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiologia , Dopamina , Sinergismo Farmacológico , Ecotoxicologia , Masculino , Síndromes Neurotóxicas/metabolismo , Oxidantes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Proteínas de Peixe-Zebra/genética
13.
Toxicology ; 465: 153058, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34863901

RESUMO

Few studies exist on the toxic effects of chronic exposure to microcystins (MCs) on amphibian intestines, and the toxicity mechanisms are unclear. Here, we evaluated the impact of subchronic exposure (30 days) to environmentally realistic microcystin-leucine arginine (MC-LR) concentrations (0 µg/L, 0.5 µg/L and 2 µg/L) on tadpole (Lithobates catesbeianus) intestines by analyzing the histopathological and subcellular microstructural damage, the antioxidative and oxidative enzyme activities, and the transcriptome levels. Histopathological results showed severe damage accompanied by inflammation to the intestinal tissues as the MC-LR exposure concentration increased from 0.5 µg/L to 2 µg/L. RNA-sequencing analysis identified 634 and 1,147 differentially expressed genes (DEGs) after exposure to 0.5 µg/L and 2 µg/L MC-LR, respectively, compared with those of the control group (0 µg/L). Biosynthesis of unsaturated fatty acids and the peroxisome proliferator-activated receptor (PPAR) signaling pathway were upregulated in the intestinal tissues of the exposed groups, with many lipid droplets being observed on transmission electron microscopy, implying that MC-LR may induce lipid accumulation in frog intestines. Moreover, 2 µg/L of MC-LR exposure inhibited the xenobiotic and toxicant biodegradation related to detoxification, implying that the tadpoles' intestinal detoxification ability was weakened after exposure to 2 µg/L MC-LR, which may aggravate intestinal toxicity. Lipid accumulation and toxin efflux disorder may be caused by MC-LR-induced endoplasmic reticular stress. This study presents new evidence that MC-LR harms amphibians by impairing intestinal lipid metabolism and toxin efflux, providing a theoretical basis for evaluating the health risks of MC-LR to amphibians.


Assuntos
Absorção Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Toxinas Marinhas/toxicidade , Microcistinas/toxicidade , Rana catesbeiana/metabolismo , Animais , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Intestinos/enzimologia , Intestinos/metabolismo , Larva/efeitos dos fármacos , Larva/genética , Larva/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Rana catesbeiana/embriologia , Rana catesbeiana/genética , Espécies Reativas de Oxigênio/metabolismo , Transcriptoma/efeitos dos fármacos
14.
Harmful Algae ; 111: 102131, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35016773

RESUMO

Although phytoplankton is ubiquitous in the world's oceans some species can produce compounds that cause damaging effects in other organisms. These include the toxins responsible for paralytic shellfish poisoning, which, in UK waters, are produced by dinoflagellates from the Alexandrium genus. Within Great Britain (GB) a monitoring programme exists to detect this harmful genus as well as the Paralytic Shellfish Poisoning (PSP) toxins in the flesh of shellfish from classified production areas. The techniques used for toxin analysis allow for detailed analysis of the toxin profiles present in contaminated shellfish. It is possible to compare the toxin profiles of contaminated shellfish with the profiles from toxin producing algae and use this information to infer the causative microalgal species responsible for the contamination. This study sought to evaluate the potential for this process within the GB monitoring framework. Two species of toxic Alexandrium, A. catenella from Scotland and A. minutum from Southern England, were fed to mussels (Mytilus sp.) under controlled conditions. The toxin profile in mussels derived from feeding on each species independently, when mixed and when introduced sequentially was analysed and compared to the source algal cultures using K means cluster analysis. Toxin profiles in contaminated shellfish clustered with those of the causative algae and separately from one another during toxin accumulation and, where A. catenella was the sole toxin source, during depuration. During depuration after feeding with A. minutum and where mixed or sequential feeding was undertaken deviant toxin profiles were observed. Finally, data generated within this experimental study were compared to monitoring data from the GB official control programme. These data indicated that the causative algal species in sole source contaminations could be inferred from toxin profile analysis. This technique will be of benefit within monitoring programmes to enhance the value of data with minimal additional expense, where the toxin profiles of causative microalgae have been well described.


Assuntos
Dinoflagelados , Mytilus , Intoxicação por Frutos do Mar , Animais , Toxinas Marinhas/toxicidade , Frutos do Mar/análise
15.
Toxins (Basel) ; 13(12)2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34941737

RESUMO

The bloom-forming toxic dinoflagellate Alexandrium catenella was first detected in southern Chile (39.5-55° S) 50 years ago and is responsible for most of the area's cases of paralytic shellfish poisoning (PSP). Given the complex life history of A. catenella, which includes benthic sexual cysts, in this study, we examined the potential link between latitude, toxicity, and sexual compatibility. Nine clones isolated from Chilean Patagonia were used in self- and out-crosses in all possible combinations (n = 45). The effect of latitude on toxicity, reproductive success indexes, and cyst production was also determined. Using the toxin profiles for all strains, consisting of C1, C2, GTX4, GTX1, GTX3, and NeoSTX, a latitudinal gradient was determined for their proportions (%) and content per cell (pg cell-1), with the more toxic strains occurring in the north (-40.6° S). Reproductive success also showed a latitudinal tendency and was lower in the north. None of the self-crosses yielded resting cysts. Rather, the production of resting cysts was highest in pairings of clones separated by distances of 1000-1650 km. Our results contribute to a better understanding of PSP outbreaks in the region and demonstrate the importance of resting cysts in fueling new toxic events. They also provide additional evidence that the introduction of strains from neighboring regions is a cause for concern.


Assuntos
Dinoflagelados/genética , Dinoflagelados/metabolismo , Toxinas Marinhas/metabolismo , Toxinas Marinhas/toxicidade , Chile , DNA Espaçador Ribossômico/genética , Eutrofização , Toxinas Marinhas/genética , Reprodução
16.
Toxins (Basel) ; 13(12)2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34941742

RESUMO

Various species of Alexandrium can produce a number of bioactive compounds, e.g., paralytic shellfish toxins (PSTs), spirolides, gymnodimines, goniodomins, and also uncharacterised bioactive extracellular compounds (BECs). The latter metabolites are released into the environment and affect a large range of organisms (from protists to fishes and mammalian cell lines). These compounds mediate allelochemical interactions, have anti-grazing and anti-parasitic activities, and have a potentially strong structuring role for the dynamic of Alexandrium blooms. In many studies evaluating the effects of Alexandrium on marine organisms, only the classical toxins were reported and the involvement of BECs was not considered. A lack of information on the presence/absence of BECs in experimental strains is likely the cause of contrasting results in the literature that render impossible a distinction between PSTs and BECs effects. We review the knowledge on Alexandrium BEC, (i.e., producing species, target cells, physiological effects, detection methods and molecular candidates). Overall, we highlight the need to identify the nature of Alexandrium BECs and urge further research on the chemical interactions according to their ecological importance in the planktonic chemical warfare and due to their potential collateral damage to a wide range of organisms.


Assuntos
Dinoflagelados/metabolismo , Toxinas Marinhas/metabolismo , Toxinas Marinhas/toxicidade , Animais , Toxinas Marinhas/química
17.
Toxins (Basel) ; 13(11)2021 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-34822605

RESUMO

Harmful algal blooms are a significant environmental problem. Cells that bloom are often associated with intercellular or dissolved toxins that are a grave concern to humans. However, cells may also excrete compounds that are beneficial to their competition, allowing the cells to establish or maintain cells in bloom conditions. Here, we develop a yeast cell assay to assess whether the bloom-forming species can change the toxicity of the water environment. The current methods of assessing toxicity involve whole organisms. Here, yeast cells are used as a bioassay model to evaluate eukaryotic cell toxicity. Yeast is a commonly used, easy to maintain bioassay species that is free from ethical concerns, yet is sensitive to a wide array of metabolic and membrane-modulating agents. Compared to methods in which the whole organism is used, this method offers rapid and convenient cytotoxicity measurements using a lower volume of samples. The flow cytometer was employed in this toxicology assessment to measure the number of dead cells using alive/dead stain analysis. The results show that yeast cells were metabolically damaged after 1 h of exposure to our model toxin-producing euryhaline flagellates (Heterosigma akashiwo and Prymnesium parvum) cells or extracts. This amount was increased by extending the incubation time.


Assuntos
Proliferação Nociva de Algas , Toxinas Marinhas/toxicidade , Modelos Biológicos , Saccharomyces cerevisiae/citologia , Animais , Peixes , Haptófitas/metabolismo , Estramenópilas/metabolismo , Fatores de Tempo
18.
Toxicology ; 464: 153021, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34740672

RESUMO

Nonalcoholic steatohepatitis (NASH) causes liver extracellular matrix (ECM) remodeling and is a risk factor for fibrosis and hepatocellular carcinoma (HCC). Microcystin-LR (MCLR) is a hepatotoxin produced by fresh-water cyanobacteria that causes a NASH-like phenotype, liver fibrosis, and is also a risk factor for HCC. The focus of the current study was to investigate and compare hepatic recovery after cessation of MCLR exposure in healthy versus NASH animals. Male Sprague-Dawley rats were fed either a control or a high fat/high cholesterol (HFHC) diet for eight weeks. Animals received either vehicle or 30 µg/kg MCLR (i.p: 2 weeks, alternate days). Animals were euthanized at one of three time points: at the completion of the MCLR exposure period and after 2 and 4 weeks of recovery. Histological staining suggested that after four weeks of recovery the MCLR-exposed HFHC group had less steatosis and more fibrosis compared to the vehicle-exposed HFHC group and MCLR-exposed control group. RNA-Seq analysis revealed dysregulation of ECM genes after MCLR exposure in both control and HFHC groups that persisted only in the HFHC groups during recovery. After 4 weeks of recovery, MCLR hepatotoxicity in pre-existing NASH persistently dysregulated genes related to cellular differentiation and HCC. These data demonstrate impaired hepatic recovery and persistent carcinogenic changes after MCLR toxicity in pre-existing NASH.


Assuntos
Matriz Extracelular/patologia , Cirrose Hepática/fisiopatologia , Toxinas Marinhas/toxicidade , Microcistinas/toxicidade , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Diferenciação Celular/genética , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Matriz Extracelular/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/genética , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
19.
Ecotoxicol Environ Saf ; 227: 112905, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34673413

RESUMO

Diarrheic shellfish poisoning (DSP) toxins are widely distributed over the world, causing diarrhea, vomiting, and even tumor in human. However, bivalves, the main carrier of the DSP toxins, have some tolerant mechanisms to DSP toxins, though it remains unclear. In this study, we scrutinized the role of Jun N-terminal kinases (JNK) in tolerance of DSP toxins and the relationship between JNK, apoptosis and nuclear factor E2-related factor/antioxidant response element (Nrf2/ARE) pathways. We found that the phosphorylated level of JNK protein was significantly increased both in hemocytes (6 h) and gills (3 h) of the mussel Perna viridis after short-term exposure to DSP toxins-producing dinoflagellate Prorocentrum lima. Exposure of P. lima induced oxidative stress in mussels. Hemocytes and gills displayed different sensitivities to the cytotoxicity of DSP toxins. Exposure of P. lima activated caspase-3 and induced apoptosis in gills but did not induce caspase-3 and apoptosis in hemocytes. The short-term exposure of P. lima could activate Nrf2/ARE signaling pathway in hemocytes (6 h), while longer-term exposure could induce glutathione reductase (GR) expression in hemocytes (96 h) and glutathione-S-transferases (GST) in gills (96 h). Based on the phylogenetic tree of Nrf2, Nrf2 in P. viridis was closely related to that in other mussels, especially Mytilus coruscus, but far from that in Mus musculus. The most likely phosphorylated site of Nrf2 in the mussels P. viridis is threonine 504 for JNK, which is different from that in M. musculus. Taken all together, the tolerant mechanism of P. viridis to DSP toxins might be involved in JNK and Nrf2/ARE signaling pathways, and JNK play a key role in the mechanism. Our findings provide a new clue to further understand tolerant mechanisms of bivalves to DSP toxins.


Assuntos
Dinoflagelados , Perna (Organismo) , Animais , Humanos , Sistema de Sinalização das MAP Quinases , Toxinas Marinhas/toxicidade , Camundongos , Filogenia
20.
Toxins (Basel) ; 13(9)2021 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-34564610

RESUMO

Nemertea is a phylum of marine worms whose members bear various toxins, including tetrodotoxin (TTX) and its analogues. Despite the more than 30 years of studying TTXs in nemerteans, many questions regarding their functions and the mechanisms ensuring their accumulation and usage remain unclear. In the nemertean Kulikovia alborostrata, we studied TTX and 5,6,11-trideoxyTTX concentrations in body extracts and in released mucus, as well as various aspects of the TTX-positive-cell excretion system and voltage-gated sodium (Nav1) channel subtype 1 mutations contributing to the toxins' accumulation. For TTX detection, an immunohistological study with an anti-TTX antibody and HPLC-MS/MS were conducted. For Nav1 mutation searching, PCR amplification with specific primers, followed by Sanger sequencing, was used. The investigation revealed that, in response to an external stimulus, subepidermal TTX-positive cells released secretions actively to the body surface. The post-release toxin recovery in these cells was low for TTX and high for 5,6,11-trideoxyTTX in captivity. According to the data obtained, there is low probability of the targeted usage of TTX as a repellent, and targeted 5,6,11-trideoxyTTX secretion by TTX-bearing nemerteans was suggested as a possibility. The Sanger sequencing revealed identical sequences of the P-loop regions of Nav1 domains I-IV in all 17 studied individuals. Mutations comprising amino acid substitutions, probably contributing to nemertean channel resistance to TTX, were shown.


Assuntos
Organismos Aquáticos/química , Toxinas Marinhas/análise , Toxinas Marinhas/toxicidade , Tetrodotoxina/biossíntese , Tetrodotoxina/toxicidade , Canais de Sódio Disparados por Voltagem/efeitos dos fármacos , Animais , Japão , Testes de Toxicidade
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