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1.
J Agric Food Chem ; 68(5): 1427-1435, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31913622

RESUMO

A number of new C-11 hydroxyl metabolites (so-called M-toxins) of paralytic shellfish toxins (PSTs) have been discovered in contaminated shellfish, and trace amounts have also been detected in some strains of PST-producing microalgae. To investigate the chemical conversion and stability of M-toxins, mussel extracts were purified with solid-phase extraction cartridges (Oasis HLB) and Biogel P-2 resin columns and four partially purified M-toxin fractions were stored at different temperatures (-20, 4, and 20 °C) and pH values (3, 4, and 5). The concentrations and profiles of M-toxins in these fractions were analyzed using liquid chromatography coupled with tandem mass spectrometry for 27 weeks. Results further confirmed the chemical conversion pathway M1 → M3 → M5 and determined for the first time two new transformation pathways: M2 → M4 → M6 and neosaxitoxin (NEO) → M10. The half-lives of M1, M2, M4, and M10 were calculated using a first-order degradation kinetics model, which indicated that the degradation of all M-toxins was dependent upon the temperature and pH, increasing with rising temperature and pH. In comparison to M4 and M10, M1 was more sensitive to the temperature, followed by M2. Results suggest that M-toxins should be maintained at a low temperature (-20 °C) and low pH (3) for their prolonged storage. M-toxins were less stable than all of the common analogues of PSTs, which may be beneficial for shellfish to achieve rapid detoxification through transformation of PSTs to M-toxins. These new findings are of significance because they enable further understanding of the metabolism of PSTs and their detoxification mechanisms in contaminated shellfish.


Assuntos
Bivalves/química , Toxinas Marinhas/química , Frutos do Mar/toxicidade , Animais , Cromatografia Líquida de Alta Pressão , Contaminação de Alimentos/análise , Concentração de Íons de Hidrogênio , Toxinas Marinhas/toxicidade , Estrutura Molecular , Frutos do Mar/análise , Espectrometria de Massas em Tandem , Temperatura Ambiente
2.
Aquat Toxicol ; 215: 105269, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31408752

RESUMO

Blooms of the dominant cyanobacterium Aphanizomenon flosaquae are frequently encountered in natural waters, and their secretion of neurotoxic paralytic shellfish toxins called aphantoxins threatens environmental safety and human health worldwide. The liver is the primary detoxification organ in animals, and its pro- and anti-inflammatory responses are important functions in the detoxification of toxins. Therefore, we investigated the response of these inflammatory factors to aphantoxins in the liver of zebrafish (Danio rerio). A. flosaquae DC-1 was sampled during blooms in Dianchi Lake, China and cultured, and the toxin was extracted and analyzed using high performance liquid chromatography. The primary constituents were gonyautoxins 1 (34.04%) and 5 (21.28%) and neosaxitoxin (12.77%). Zebrafish were injected intraperitoneally with 5.3 µg (low dose) or 7.61 µg (high dose) of saxitoxin equivalents [equivalents (eq.)]/kg body weight of A. flosaquae DC-1 aphantoxins. Hyperemia, the hepatosomatic index (HSI), and physiological and molecular responses of pro- and anti-inflammatory cytokines in the zebrafish liver were investigated at different time points 1-24 h post-exposure. Aphantoxins significantly enhanced hepatic hyperemia and altered the HSI 3-24 h post-exposure, suggesting that inflammation caused morphological changes. Subsequent investigations using the enzyme-linked immunosorbent assay showed that the pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1ß (IL-1ß), IL-6, and IL-8 and anti-inflammatory cytokines IL-10 and transforming growth factor ß were higher in the liver of zebrafish exposed to aphantoxins, which indicated physiological inflammatory responses. Further analysis by real-time fluorescence quantitative polymerase chain reaction demonstrated upregulated mRNA expression of these cytokines, suggesting molecular inflammatory responses in the zebrafish liver. These changes showed dose- and time-dependent patterns. These results indicated that aphantoxins induced hyperemia and altered the HSI, and subsequently increased the levels of proinflammatory cytokines TNF-α, IL-1ß, IL-6 and IL-8 to induce physiological inflammatory responses. These changes activated the anti-inflammatory cytokines IL-10 and TGF-ß to suppress inflammatory damage. The induced changes were the result of upregulated mRNA expression of these inflammatory cytokines caused by aphantoxins. Aphantoxins resulted in hepatic immunotoxicity and response by inducing pro-inflammatory cytokines. Zebrafish liver in turn suppressed the inflammatory damage by upregulating the activities of anti-inflammatory cytokines. In the future, these pro- and anti-inflammatory cytokines in the zebrafish liver may be prove to be useful biomarkers of aphantoxins and blooms in nature.


Assuntos
Anti-Inflamatórios/metabolismo , Aphanizomenon/química , Toxinas Bacterianas/toxicidade , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Toxinas Marinhas/toxicidade , Peixe-Zebra/metabolismo , Animais , Citocinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperemia/genética , Hiperemia/patologia , Fígado/efeitos dos fármacos , Masculino , Poluentes Químicos da Água/toxicidade
3.
Food Chem ; 298: 125011, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31261011

RESUMO

A scallop midgut gland certified reference material, NMIJ CRM 7520-a, was developed for validation and quality assurance during the inspection of shellfish for diarrhetic shellfish toxins. The candidate material was prepared by using naturally-toxic and nontoxic boiled midgut glands spiked with okadaic acid (OA). The homogeneity and stability of the material were found to be appropriate. For the characterization of OA and dinophysistoxin-1 (DTX1), nine participants were involved in a co-laboratory study based on the Japanese Official Testing Method, where the compounds were assayed by liquid chromatography-tandem mass spectrometry following alkaline hydrolysis. The analytical values were obtained by the standard addition method with a standard spiking solution calibrated using the standard-solution certified reference materials OA and DTX1. The certified concentrations with expanded uncertainties (coverage factor k = 2, approximate 95% confidence interval) were determined to be (0.205 ±â€¯0.061) mg/kg for OA and (0.45 ±â€¯0.11) mg/kg for DTX1.


Assuntos
Diarreia/complicações , Toxinas Marinhas/análise , Pectinidae/química , Piranos/análise , Frutos do Mar/análise , Animais , Calibragem , Cromatografia Líquida , Humanos , Intestinos/química , Toxinas Marinhas/normas , Toxinas Marinhas/toxicidade , Ácido Okadáico/análise , Piranos/normas , Piranos/toxicidade , Padrões de Referência , Intoxicação por Frutos do Mar/complicações , Espectrometria de Massas em Tandem
4.
Mar Drugs ; 17(7)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340532

RESUMO

In vitro and in vivo studies have shown that phycotoxins can impact intestinal epithelial cells and can cross the intestinal barrier to some extent. Therefore, phycotoxins can reach cells underlying the epithelium, such as enteric glial cells (EGCs), which are involved in gut homeostasis, motility, and barrier integrity. This study compared the toxicological effects of pectenotoxin-2 (PTX2), yessotoxin (YTX), okadaic acid (OA), azaspiracid-1 (AZA1), 13-desmethyl-spirolide C (SPX), and palytoxin (PlTX) on the rat EGC cell line CRL2690. Cell viability, morphology, oxidative stress, inflammation, cell cycle, and specific glial markers were evaluated using RT-qPCR and high content analysis (HCA) approaches. PTX2, YTX, OA, AZA1, and PlTX induced neurite alterations, oxidative stress, cell cycle disturbance, and increase of specific EGC markers. An inflammatory response for YTX, OA, and AZA1 was suggested by the nuclear translocation of NF-κB. Caspase-3-dependent apoptosis and induction of DNA double strand breaks (γH2AX) were also observed with PTX2, YTX, OA, and AZA1. These findings suggest that PTX2, YTX, OA, AZA1, and PlTX may affect intestinal barrier integrity through alterations of the human enteric glial system. Our results provide novel insight into the toxicological effects of phycotoxins on the gut.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Toxinas Marinhas/toxicidade , Neuroglia/efeitos dos fármacos , Intoxicação por Frutos do Mar/etiologia , Frutos do Mar/toxicidade , Animais , Bivalves/parasitologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dinoflagelados/química , Humanos , Mucosa Intestinal/inervação , Mucosa Intestinal/patologia , Neuroglia/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Frutos do Mar/parasitologia
5.
Chemosphere ; 234: 62-69, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31203042

RESUMO

Heat shock proteins 70KD (Hsp70s) are highly conserved molecular chaperones with essential roles against biotic and abiotic stressors. Marine bivalves inhabit highly complex environments and could accumulate paralytic shellfish toxins (PSTs), the well-noted neurotoxins generated during harmful algal blooms. Here, we systematically analyzed Hsp70 genes (CfHsp70s) in Zhikong scallop (Chlamys farreri), an important aquaculture mollusk in China. Sixty-five CfHsp70s from eight sub-families were identified, and 47 of these genes showed expansion in the Hspa12 sub-family. After exposure to different PST-producing dinoflagellates, Alexandrium minutum and Alexandrium catenella, diverse CfHsp70s regulation presented in scallop hepatopancreas, mainly accumulating incoming PSTs, and kidneys, transforming PSTs into higher toxic analogs. All the up-regulated CfHsp70s were from CfHsp70B2, CfHspa12, and CfHspa5 sub-families. CfHsp70B2 sub-family was mainly induced in the hepatopancreas, and CfHspa12 sub-family was highly induced in the kidneys. CfHsp70s up-regulation under two dinoflagellates exposure was stronger in the kidneys (log2FC: 19.5 and 18.6) than that in hepatopancreas (log2FC: 4.3 and 6.1). Exposure to different Alexandrium species had varying effects, that in hepatopancreas, CfHsp70B2s were chronically induced only after A. catenella exposure, whereas in kidney, CfHspa12s were more acutely induced after exposure of A. minutum than A. caenella. Moreover, in Yesso scallops (Patinopecten yessoensis), only Hspa12s were up-regulated in hepatopancreas after A. catenella exposure, and all the Hsp70B2s were down-regulated. These organ-, toxin-, and species-dependent Hsp70 regulation suggested the functional diversity of duplicated Hsp70s in response to the stress by PST-producing algae. Our findings provide insights into the evolution and functional characteristics of Hsp70s in scallops.


Assuntos
Dinoflagelados/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Toxinas Marinhas/toxicidade , Pectinidae/genética , Animais , Proteínas de Choque Térmico HSP70/metabolismo , Pectinidae/efeitos dos fármacos , Pectinidae/crescimento & desenvolvimento
6.
Aquat Toxicol ; 212: 37-46, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055221

RESUMO

Harmful algal blooms can adversely affect different levels of the trophic chain, from primary consumers, such as bivalve molluscs, to higher links such as large fish, birds and mammals, including humans. Among secondary consumers, it has been described that carnivorous gastropods can accumulate these toxins when they prey on bivalves that have been exposed to toxic microalgae; these could also harm human health. In Chile, frequent events of harmful algal blooms caused by the dinoflagellate Alexandrium catenella have been described. This organism produces paralytic shellfish toxin (PST) which has been identified in some carnivorous gastropods. The objective of this research was to identify the physiological and reproductive response of the carnivorous gastropod Acanthina monodon fed on the Mytilid Perumytilus purpuratus, which had previously been maintained on a diet containing PST. Specimens of A. monodon showed a decrease in ingestion and absorption rate when they consumed PST indirectly through their diet. The oxygen consumption rate was also affected by the diet-time interaction. The variations of these parameters were reflected in the scope for growth, since the available energy was lower in gastropods exposed to toxic diet. Consumption of PST had a negative effect on the reproduction of A. monodon, since intoxicated adults presented lower egg-masses and delayed start of oviposition. We observed a delay in the development of the embryos inside the capsules, and a lower number of hatched juveniles, although these few juveniles from intoxicated parents accomplished higher growth rates during the next 6 months. We may therefore suggest that toxin transfer, from harmful microalgae through the trophic chain, can generate deleterious effects on the physiological energetics of the organisms that consume them, affecting their reproductive capacity and early ontogenetic development.


Assuntos
Cadeia Alimentar , Gastrópodes/fisiologia , Toxinas Marinhas/toxicidade , Animais , Ingestão de Alimentos , Desenvolvimento Embrionário/efeitos dos fármacos , Gastrópodes/efeitos dos fármacos , Gastrópodes/embriologia , Gastrópodes/crescimento & desenvolvimento , Proliferação Nociva de Algas , Consumo de Oxigênio/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
7.
Mar Drugs ; 17(5)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31072021

RESUMO

BACKGROUND: Azaspiracids (AZAs) are marine toxins that are produced by Azadinium and Amphidoma dinoflagellates that can contaminate edible shellfish inducing a foodborne poisoning in humans, which is characterized by gastrointestinal symptoms. Among these, AZA1, -2, and -3 are regulated in the European Union, being the most important in terms of occurrence and toxicity. In vivo studies in mice showed that, in addition to gastrointestinal effects, AZA1 induces liver alterations that are visible as a swollen organ, with the presence of hepatocellular fat droplets and vacuoles. Hence, an in vitro study was carried out to investigate the effects of AZA1, -2, and -3 on liver cells, using human non-tumor IHH hepatocytes. RESULTS: The exposure of IHH cells to AZA1, -2, or -3 (5 × 10-12-1 × 10-7 M) for 24 h did not affect the cell viability and proliferation (Sulforhodamine B assay and 3H-Thymidine incorporation assay), but they induced a significant concentration-dependent increase of mitochondrial dehydrogenases activity (MTT reduction assay). This effect depends on the activity of mitochondrial electron transport chain complex I and II, being counteracted by rotenone and tenoyl trifluoroacetone, respectively. Furthermore, AZAs-increased mitochondrial dehydrogenase activity was almost totally suppressed in the K+-, Cl--, and Na+-free media and sensitive to the specific inhibitors of KATP and hERG potassium channels, Na+/K+, ATPase, and cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. CONCLUSIONS: These results suggest that AZA mitochondrial effects in hepatocytes derive from an imbalance of intracellular levels of K+ and, in particular, Cl- ions, as demonstrated by the selective reduction of toxin effects by CFTR chloride channel inhibition.


Assuntos
Furanos/toxicidade , Toxinas Marinhas/toxicidade , Mitocôndrias/efeitos dos fármacos , Oxirredutases/efeitos dos fármacos , Piranos/toxicidade , Compostos de Espiro/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cloro , Citoproteção/efeitos dos fármacos , Complexo I de Transporte de Elétrons , Complexo II de Transporte de Elétrons , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Mytilus edulis , Oxirredutases/metabolismo , Potássio
8.
J Zoo Wildl Med ; 50(1): 33-44, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31120660

RESUMO

Harmful algal blooms (HABs) occur when excess nutrients allow dinoflagellates to reproduce in large numbers. Marine animals are affected by blooms when algal toxins are ingested or inhaled. In the Gulf of Mexico, near annual blooms of Karenia brevis release a suite of compounds (brevetoxins) that cause sea turtle morbidity and mortality. The primary treatment at rehabilitation facilities for brevetoxin-exposed sea turtles is supportive care, and it has been difficult to design alternative treatment strategies without an understanding of the effects of brevetoxins in turtles in vivo. Previous studies using the freshwater turtle as a model species showed that brevetoxin-3 impacts the nervous and muscular systems, and is detoxified and eliminated primarily through the liver, bile, and feces. In this study, freshwater turtles (Trachemys scripta) were exposed to brevetoxin (PbTx-3) intratracheally at doses causing clear systemic effects, and treatment strategies aimed at reducing the postexposure neurological and muscular deficits were tested. Brevetoxin-exposed T. scripta displayed the same behaviors as animals admitted to rehabilitation centers for toxin exposure, ranging from muscle twitching and incoordination to paralysis and unresponsiveness. Two treatment regimes were tested: cholestyramine, a bile acid sequestrant; and an intravenous lipid emulsion treatment (Intralipidt) that provides an expanded circulating lipid volume. Cholestyramine was administered orally 1 hr and 6 hr post PbTx-3 exposure, but this regime failed to increase toxin clearance. Animals treated with Intralipid (100 mg/kg) 30 min after PbTx-3 exposure had greatly reduced symptoms of brevetoxicosis within the first 2 hr compared with animals that did not receive the treatment, and appeared fully recovered within 24 hr compared with toxin-exposed control animals that did not receive Intralipid. The results strongly suggest that Intralipid treatment for lipophilic toxins such as PbTx-3 has the potential to reduce morbidity and mortality in HAB-exposed sea turtles.


Assuntos
Emulsões Gordurosas Intravenosas/uso terapêutico , Toxinas Marinhas/toxicidade , Neurotoxinas/toxicidade , Oxocinas/toxicidade , Envenenamento/veterinária , Substâncias Protetoras/uso terapêutico , Tartarugas/fisiologia , Animais , Resina de Colestiramina/uso terapêutico , Envenenamento/tratamento farmacológico
9.
Sci Total Environ ; 673: 327-336, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-30991322

RESUMO

A strategy to construct multivariate biomarkers for exposure to algal neurotoxins via correlating changes to the profiles of a series of neurotransmitters and their metabolites in the central nervous system (CNS) of exposed test organism is reported. 3-Month-old marine medaka (Oryzais melastigma) were exposed to waterborne brevetoxin PbTx-1 at two sub-lethal dose levels (0.5 and 2.5 µg-PbTx-1 L-1) for a duration of 12 h before quantification of 43 selected neurotransmitters and metabolites in their CNS were measured via dansyl chloride derivatization and LC-MS/MS determination. The profiling data were analyzed by multivariate statistical analyses, including principle component analysis (PCA), projection on latent structure-discriminate analysis (PLS-DA) and orthogonal projection on latent structure-discriminate analysis (OPLS-DA). Neurotransmitters and metabolites related to activation of voltage-gated sodium channels (VGSCs), N-methyl-D-aspartic acid receptors (NMDARs) and cholinergic neurotransmission were found to contribute significantly to class separation in the corresponding OPLS-DA models. Those models obtained from different exposure dosages were correlated by the Shared and Unique Structures Plot (SUS-plot) to identify appropriate variables for the construction of exposure biomarkers in the form of multivariate predictive scores. The established biomarkers for male and female medaka fish were able to predict acute sub-lethal exposure to PbTx-1 with good sensitivity and specificity (male fish: sensitivity 94.7%, specificity 80.0%; female fish: sensitivity 91.4%, specificity 83.3%). Neurotransmitter profiles in the CNS of medaka fish that should have recovered from exposure to PbTx-1 have also been determined to reveal long-term impacts to the CNS of the affected organism even after the exposure has been interrupted.


Assuntos
Toxinas Marinhas/toxicidade , Sistema Nervoso/efeitos dos fármacos , Neurotransmissores/metabolismo , Oryzias/fisiologia , Oxocinas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , Feminino , Masculino , Neurotoxinas
10.
Mar Drugs ; 17(4)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30965587

RESUMO

A novel protein, soritesidine (SOR) with potent toxicity was isolated from the marine sponge Spongosorites sp. SOR exhibited wide range of toxicities over various organisms and cells including brine shrimp (Artemia salina) larvae, sea hare (Aplysia kurodai) eggs, mice, and cultured mammalian cells. Toxicities of SOR were extraordinary potent. It killed mice at 5 ng/mouse after intracerebroventricular (i.c.v.) injection, and brine shrimp and at 0.34 µg/mL. Cytotoxicity for cultured mammalian cancer cell lines against HeLa and L1210 cells were determined to be 0.062 and 12.11 ng/mL, respectively. The SOR-containing fraction cleaved plasmid DNA in a metal ion dependent manner showing genotoxicity of SOR. Purified SOR exhibited molecular weight of 108.7 kDa in MALDI-TOF MS data and isoelectric point of approximately 4.5. N-terminal amino acid sequence up to the 25th residue was determined by Edman degradation. Internal amino acid sequences for fifteen peptides isolated from the enzyme digest of SOR were also determined. None of those amino acid sequences showed similarity to existing proteins, suggesting that SOR is a new proteinous toxin.


Assuntos
Toxinas Marinhas/toxicidade , Poríferos , Sequência de Aminoácidos , Animais , Aplysia/efeitos dos fármacos , Artemia/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Bioensaio/métodos , Linhagem Celular Tumoral , Humanos , Japão , Larva/efeitos dos fármacos , Masculino , Toxinas Marinhas/administração & dosagem , Toxinas Marinhas/química , Toxinas Marinhas/isolamento & purificação , Camundongos , Peso Molecular , Testes de Mutagenicidade/métodos
11.
Toxins (Basel) ; 11(4)2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934869

RESUMO

In late February 2016, a harmful algal bloom (HAB) of Alexandrium catenella was detected in southern Chiloé, leading to the banning of shellfish harvesting in an extended geographical area (~500 km). On April 24, 2016, this bloom produced a massive beaching (an accumulation on the beach surface of dead or impaired organisms which were drifted ashore) of surf clams Mesodesma donacium in Cucao Bay, Chiloé. To determine the effect of paralytic shellfish poisoning (PSP) toxins in M. donacium, samples were taken from Cucao during the third massive beaching detected on May 3, 2016. Whole tissue toxicity evidence a high interindividual variability with values which ranged from 1008 to 8763 µg STX eq 100 g-1 and with a toxin profile dominated by GTX3, GTX1, GTX2, GTX4, and neoSTX. Individuals were dissected into digestive gland (DG), foot (FT), adductor muscle (MU), and other body fractions (OBF), and histopathological and toxin analyses were carried out on the obtained fractions. Some pathological conditions were observed in gill and digestive gland of 40⁻50% of the individuals that correspond to hemocyte aggregation and haemocytic infiltration, respectively. The most toxic tissue was DG (2221 µg STX eq 100 g-1), followed by OBF (710 µg STX eq 100 g-1), FT (297 µg STX eq 100 g-1), and MU (314 µg STX eq 100 g-1). The observed surf clam mortality seems to have been mainly due to the desiccation caused by the incapability of the clams to burrow. Considering the available information of the monitoring program and taking into account that this episode was the first detected along the open coast of the Pacific Ocean in southern Chiloé, it is very likely that the M. donacium population from Cucao Bay has not had a recurrent exposition to A. catenella and, consequently, that it has not been subjected to high selective pressure for PSP resistance. However, more research is needed to determine the effects of PSP toxins on behavioral and physiological responses, nerve sensitivity, and genetic/molecular basis for the resistance or sensitivity of M. donacium.


Assuntos
Bivalves/química , Bivalves/efeitos dos fármacos , Dinoflagelados , Proliferação Nociva de Algas , Toxinas Marinhas/análise , Toxinas Marinhas/toxicidade , Animais , Chile , Hemócitos , Intoxicação por Frutos do Mar
12.
Arch. Soc. Esp. Oftalmol ; 94(4): 184-187, abr. 2019. ilus
Artigo em Espanhol | IBECS | ID: ibc-183302

RESUMO

Describir un caso de toxicidad corneal secundaria a exposición a palitoxina. Un hombre de 42 años acude por dolor y visión borrosa en su ojo derecho de una semana de evolución. Como antecedente destaca la entrada de un líquido procedente de un coral (Palythoa sp). En la biomicroscopia se observa un infiltrado central en forma de anillo de 4 × 6mm sin defecto epitelial y con microinfiltrados subepiteliales satélites. Después de 2 meses de tratamiento tópico con esteroides se resuelve el infiltrado, pero persiste una fibrosis y adelgazamiento estromal paracentral. La palitoxina es un potente vasoconstrictor que daña el gradiente iónico de las células provocando muerte celular. Es crucial retirar la toxina e iniciar una terapia intensiva con corticoides tópicos lo antes posible. Asimismo, teniendo en cuenta los efectos adversos oculares y sistémicos, sería conveniente informar a la población de su existencia y regular la distribución de este tipo de corales


A case is presented of corneal toxicity after exposure to palytoxin. A 42 year-old man came with symptoms of pain and blurred vision in his right eye. He reported that a zoanthid coral from a saltwater aquarium had squirted into his eye. Slit-lamp examination showed a prominent central ring infiltrate of 4 × 6mm without epithelial defect and satellite sub-epithelial micro-infiltrates. After 2 months of topical treatment with steroids, the stromal ring infiltrate was resolved, but a stromal thinning and residual fibrosis remained. Palytoxin is a potent vasoconstrictor that damages the ionic gradient of the cells, causing cell death. It is crucial to remove the toxin and start an aggressive topical therapy as soon as possible. In addition, considering the potential ocular and systemic adverse effects that this toxin can produce, it would be advisable to inform people of its existence and regulate the distribution of this type of corals


Assuntos
Humanos , Masculino , Adulto , Antozoários/química , Toxinas Marinhas/toxicidade , Doenças da Córnea/diagnóstico , Doenças da Córnea/etiologia , Doenças da Córnea/tratamento farmacológico , Microscopia Confocal , Prednisolona/uso terapêutico , Doxiciclina/uso terapêutico
13.
Neurotoxicology ; 72: 114-124, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30826346

RESUMO

Domoic acid (DA) is an excitatory neurotoxin produced by marine algae and responsible for Amnesiac Shellfish Poisoning in humans. Current regulatory limits (˜0.075-0.1 mg/kg/day) protect against acute toxicity, but recent studies suggest that the chronic consumption of DA below the regulatory limit may produce subtle neurotoxicity in adults, including decrements in memory. As DA-algal blooms are increasing in both severity and frequency, we sought to better understand the effects of chronic DA exposure on reproductive and neurobehavioral endpoints in a preclinical nonhuman primate model. To this end, we initiated a long-term study using adult, female Macaca fascicularis monkeys exposed to daily, oral doses of 0.075 or 0.15 mg/kg of DA for a range of 321-381, and 346-554 days, respectively. This time period included a pre-pregnancy, pregnancy, and postpartum period. Throughout these times, trained data collectors observed intentional tremors in some exposed animals during biweekly clinical examinations. The present study explores the basis of this neurobehavioral finding with in vivo imaging techniques, including diffusion tensor magnetic resonance imaging and spectroscopy. Diffusion tensor analyses revealed that, while DA exposed macaques did not significantly differ from controls, increases in DA-related tremors were negatively correlated with fractional anisotropy, a measure of structural integrity, in the internal capsule, fornix, pons, and corpus callosum. Brain concentrations of lactate, a neurochemical closely linked with astrocytes, were also weakly, but positively associated with tremors. These findings are the first documented results suggesting that chronic oral exposure to DA at concentrations near the current human regulatory limit are related to structural and chemical changes in the adult primate brain.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Ácido Caínico/análogos & derivados , Toxinas Marinhas/toxicidade , Neurotoxinas/toxicidade , Animais , Imagem de Tensor de Difusão , Feminino , Ácido Caínico/administração & dosagem , Ácido Caínico/toxicidade , Macaca fascicularis , Toxinas Marinhas/administração & dosagem , Neurotoxinas/administração & dosagem , Período Pós-Parto , Gravidez , Tremor/induzido quimicamente
14.
Toxicon ; 161: 44-49, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30826470

RESUMO

Marine toxins are known among several causes of toxin induced renal injury. Enzymatic mechanism by phospholipase A2 is responsible for acute kidney injury (AKI) in sea snake envenoming without any change in cardiac output and systemic vascular resistance. Cnidarian toxins form pores in the cell membrane with Ca influx storm resulting in cell death. Among plankton toxins domoic acid, palytoxin and maitotoxin cause renal injury by ion transport into the cell through ion channels resulting in renal cell swelling and lysis. Okadaic acid, calyculin A, microcystin LR and nodularin cause AKI by serine threonine phosphatase inhibition and hyperphosphorylation with increased activity of Ca2+/calmodulin - dependent protein kinase II, increased cytosolic Ca2+, reactive oxygen species, caspase and P53. Renal injury by plankons is mostly subclinical and requires sensitive biomarker for diagnosis. In this respect repeated consumption of plankton toxin contaminated seafood is a risk of developing chronic renal disease. The subject deserves more clinical study and scientific attention.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Toxinas Marinhas/envenenamento , Toxinas Marinhas/toxicidade , Lesão Renal Aguda/metabolismo , Animais , Humanos
15.
Toxicol In Vitro ; 58: 150-160, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30926360

RESUMO

Okadaic acid (OA) is a lipophilic phycotoxin that accumulates in the hepatopancreas and fatty tissue of shellfish. Consumption of highly OA-contaminated seafood leads to diarrhetic shellfish poisoning which provokes severe gastrointestinal symptoms associated with a disruption of the intestinal epithelium. Since the molecular mechanisms leading to intestinal barrier disruption are not fully elucidated, we investigated the influence of OA on intestinal tight junction proteins (TJPs) in differentiated Caco-2 cells. We found a concentration- and time-dependent deregulation of genes encoding for intestinal TJPs of the claudin family, occludin, as well as zonula occludens (ZO) 1 and 2. Immunofluorescence staining showed concentration-dependent effects on the structural organization of TJPs already after treatment with a subtoxic but human-relevant concentration of OA. In addition, changes in the structural organization of cytoskeletal F-actin as well as its associated protein ZO-1 were observed. In summary, we demonstrated effects of OA on TJPs in intestinal Caco-2 cells. TJP expressions were affected after treatment with food-relevant OA concentrations. These results might explain the high potential of OA to disrupt the intestinal barrier in vivo as its first target. Thereby the present data contribute to a better understanding of the OA-dependent induction of molecular effects within the intestinal epithelium.


Assuntos
Toxinas Marinhas/toxicidade , Ácido Okadáico/toxicidade , Proteínas de Junções Íntimas/metabolismo , Células CACO-2 , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Proteínas de Junções Íntimas/genética
16.
Ecotoxicol Environ Saf ; 176: 178-185, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30927639

RESUMO

Diarrhetic shellfish poisoning (DSP) toxins are key shellfish toxins that cause diarrhea, vomiting and even tumor. Interestingly, bivalves such as Perna viridis have been reported to exhibit some resistances to alleviate toxic effects of DSP toxins in a species-specific manner. Nevertheless, the molecular mechanisms underlying the resistance phenomenon to DSP toxins, particularly the mechanistic role of CYP450 is scant despite its crucial role in detoxification. Here, we exposed P. viridis to Prorocentrum lima and examined the expression pattern of the CYP450 and our comprehensive analyses revealed that P. lima exposure resulted in unique expression pattern of key CYP450 genes in bivalves. Exposure to P. lima (2 × 105 cells/L) dramatically orchestrated the relative expression of CYP450 genes. CYP2D14-like mRNA was significantly down-regulated at 6 h in gill, but up-regulated at 2 h in digestive gland compared with control counterparts (p < 0.05), while CYP3A4 mRNA was increased at 12 h in gill. After exposure to P. lima at 2 × 106 cells/L, the expression of CYP3A4 mRNA was significantly increased in digestive gland at 2 h and 12 h, while CYP2D14-like was up-regulated at 6 h. Besides, CYP3L3 and CYP2C8 also exhibited differential expression. These data suggested that CYP3A4, CYP2D14-like, and even CYP3L3 and CYP2C8 might be involved in DSP toxins metabolism. Besides, provision of ketoconazole resulted in significant decrement of CYP3A4 in digestive gland at 2 h and 12 h, while the OA content significantly decreased at 2 h and 6 h compared to control group without ketoconazole. These findings indicated that ketoconazole could depress CYP3A4 activity in bivalves thereby altering the metabolic activities of DSP toxins in bivalves, and also provided novel insights into the mechanistic role of CYP3A4 on DSP toxins metabolism in bivalves.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Dinoflagelados/metabolismo , Toxinas Marinhas/toxicidade , Perna (Organismo)/enzimologia , Intoxicação por Frutos do Mar , Poluentes da Água/toxicidade , Animais , Sistema Enzimático do Citocromo P-450/genética , Brânquias/efeitos dos fármacos , Brânquias/enzimologia , Perna (Organismo)/efeitos dos fármacos , Alimentos Marinhos/análise
17.
Artigo em Inglês | MEDLINE | ID: mdl-30724672

RESUMO

Okadaic acid group (OA-group) is a set of lipophilic toxins which are characterised by being produced by species associated with the genera Dinophysis and Prorocentrum. OA-group has been regularly detected in endemic shellfish species from the southern zone of Chile only through the mouse bioassay. The purpose of this work was to determine the variability of OA-group toxins in endemic aquatic organisms (bivalves, crabs, gastropods and fish) and to establish the relationship with the concentration of fatty acids (FAs) detected in the evaluated species. The toxicity of OA-group and the FA profiles were determined using LC-MS/MS and gas chromatography with flame-ionisation detection, respectively. In the study area, the dinoflagellate Dinophysis acuta was detected in densities ≈2000 cells ml-1 with a toxicity ≈18.3 pg OA equiv cel-1. The analysis identified OA and dinophysistoxin-1 in shellfish in a range of ≈90 to ≈225 µg OA eq kg-1, where no toxins in fish were detected. A positive relationship between the FA level and the concentration of OA-group toxins in the digestive glands of bivalves and gastropods was established, noted for high levels of saturated FAs (C14:0 and C16:0). The toxic variability of OA-group toxins determined in the different species allowed us to establish that the consumption of these vectors, regulated by non-analytical methods, can be harmful when consumed by humans, thus suggesting that the sanitary regulations for the control of OA-group in Chile should be updated.


Assuntos
Organismos Aquáticos/química , Ácidos Graxos/análise , Toxinas Marinhas/química , Toxinas Marinhas/toxicidade , Ácido Okadáico/química , Ácido Okadáico/toxicidade , Animais , Bivalves/química , Braquiúros/química , Cromatografia Líquida , Peixes , Gastrópodes/química , Especificidade da Espécie , Espectrometria de Massas em Tandem
18.
Toxins (Basel) ; 11(2)2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30736356

RESUMO

Some species of the genus Pseudo-nitzschia produce the toxin domoic acid, which causes amnesic shellfish poisoning (ASP). Given that bivalve mollusks are filter feeders, they can accumulate these toxins in their tissues. To elucidate the transcriptional response of the queen scallop Aequipecten opercularis after exposure to domoic acid-producing Pseudo-nitzschia, the digestive gland transcriptome was de novo assembled using an Illumina HiSeq 2000 platform. Then, a differential gene expression analysis was performed. After the assembly, 142,137 unigenes were obtained, and a total of 10,144 genes were differentially expressed in the groups exposed to the toxin. Functional enrichment analysis found that 374 Pfam (protein families database) domains were significantly enriched. The C1q domain, the C-type lectin, the major facilitator superfamily, the immunoglobulin domain, and the cytochrome P450 were among the most enriched Pfam domains. Protein network analysis showed a small number of highly connected nodes involved in specific functions: proteasome components, mitochondrial ribosomal proteins, protein translocases of mitochondrial membranes, cytochromes P450, and glutathione S-transferases. The results suggest that exposure to domoic acid-producing organisms causes oxidative stress and mitochondrial dysfunction. The transcriptional response counteracts these effects with the up-regulation of genes coding for some mitochondrial proteins, proteasome components, and antioxidant enzymes (glutathione S-transferases, thioredoxins, glutaredoxins, and copper/zinc superoxide dismutases).


Assuntos
Trato Gastrointestinal/efeitos dos fármacos , Ácido Caínico/análogos & derivados , Toxinas Marinhas/toxicidade , Pectinidae/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Animais , Diatomáceas , Trato Gastrointestinal/metabolismo , Ácido Caínico/toxicidade , Pectinidae/genética
19.
Org Lett ; 21(2): 356-359, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30601015

RESUMO

Azaspiracid-34 (AZA34) is a recently described structurally unique member of the azaspiracid class of marine neurotoxins. Its novel structure, tentatively assigned on the basis of MS and 1H NMR spectroscopy, is accompanied by a 5.5-fold higher level of toxicity against Jurkat T lymphocytes than AZA1. To completely assign the structure of AZA34 and provide material for in-depth biological evaluation and detection, synthetic access to AZA34 was targeted. This began with the convergent and stereoselective assembly of the C1-C19 domain of AZA34 designed to dovetail with the recent total synthesis approach to AZA3.


Assuntos
Células Jurkat/citologia , Toxinas Marinhas/toxicidade , Neurotoxinas/toxicidade , Compostos de Espiro/síntese química , Humanos , Células Jurkat/química , Espectroscopia de Ressonância Magnética , Toxinas Marinhas/síntese química , Toxinas Marinhas/química , Estrutura Molecular , Compostos de Espiro/química
20.
Toxicon ; 160: 1-7, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30639658

RESUMO

Okadaic acid (OA), a potent polyether marine toxin, accumulates in the digestive glands of marine mollusks and therefore can severely threaten the health of humans after ingestion of contaminated shellfish. In vivo and in vitro studies have revealed that exposure of various cells, including human embryonic amniotic cells, hepatocytes, neuroblastoma cells, to OA induces morphological and functional modifications as well as the death of cells. As the number of reports on OA poisoning has increased, this toxin has gradually attracted the public's attention, and researchers are trying to study it. This review summarizes the current literature on the toxicity effects of OA, in addition to its detection and detoxification.


Assuntos
Dinoflagelados/química , Ácido Okadáico/toxicidade , Animais , Humanos , Inativação Metabólica , Toxinas Marinhas/toxicidade , Moluscos/química , Ácido Okadáico/análise , Ácido Okadáico/metabolismo , Intoxicação por Frutos do Mar
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