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1.
PLoS One ; 15(2): e0228414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32032360

RESUMO

As reef-building corals are increasingly being exposed to persistent threats that operate on both regional and global scales, there is a pressing need to better understand the complex processes that diminish coral populations. This study investigated the impacts of the Florida red tide dinoflagellate Karenia brevis and associated brevetoxins on selected facets of coral biology using Porites astreoides as a model system. When provided with choice assays, P. astreoides larvae were shown to actively avoid seawater containing red tide (5×105 cells L-1-7.6×106 cells L-1) or purified brevetoxins (0.018 µg mL-1 brevetoxin-2 and 0.0018 µg mL-1 brevetoxin-3). However, forced exposure to similar treatments induced time-dependent physiological and behavioral changes that were captured by PAM fluorometry and settlement and survival assays, respectively. Adult fragments of P. astreoides exposed to red tide or associated brevetoxins displayed signs of proteomic alterations that were characterized by the use of an iTRAQ-based quantitative proteomic analysis. The novel use of this technique with P. astreoides demonstrated that protein regulation was highly contingent upon biological versus chemical treatment (i.e. live K. brevis vs. solely brevetoxin exposure) and that several broad pathways associated with cell stress were affected including redox homeostasis, protein folding, energy metabolism and reactive oxygen species production. The results herein provide new insight into the ecology, behavior and sublethal stress of reef-building corals in response to K. brevis exposure and underscore the importance of recognizing the potential of red tide to act as a regional stressor to these important foundation species.


Assuntos
Dinoflagelados/patogenicidade , Ecossistema , Exposição Ambiental/efeitos adversos , Proliferação Nociva de Algas/fisiologia , Larva/metabolismo , Toxinas Marinhas/toxicidade , Oxocinas/toxicidade , Proteoma/análise , Animais , Proliferação Nociva de Algas/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Proteômica
2.
Aquat Toxicol ; 218: 105371, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790939

RESUMO

Harmful algal bloom (HAB) toxins have severe negative impacts on marine mammals, particularly for Florida bottlenose dolphins (Tursiops truncatus) which frequently experience mass mortality events. Dolphins on the Florida Atlantic coast inhabit a region endemic to two HAB species, Karenia brevis and Pyrodinium bahamense, which produce the neurotoxins brevetoxin (PbTx) and saxitoxin (STX), respectively. Although toxic HABs and associated dolphin mortality events have been reported from this region, there is a lack of available data necessary for comparing toxin exposure levels between bloom ('exposed') conditions and non-bloom ('baseline') conditions. Here we present a 10-year dataset of PbTx and STX concentrations detected in dolphins stranding in this region, and compare the toxin loads from HAB-exposed dolphins to those detected in dolphins recovered in the absence of a HAB. We analyzed liver tissue samples from dead-stranded dolphins (n = 119) recovered and necropsied between 2002-2011, using an enzyme-linked immunosorbent assay (ELISA) modified for use with mammalian tissues. For dolphins recovered during baseline conditions, toxin-positive samples ranged in concentration from 0.27 to 1.2 ng/g for PbTx and from 0.41 to 1.9 ng/g for STX. For K. brevis-exposed dolphins, concentrations of up to 12.1 ng PbTx/g were detected, and for P. bahamense-exposed dolphins, concentrations of up to 9.9 ng STX/g were detected. Baseline PbTx values were similar to those reported in other regions where K. brevis blooms are more frequent and severe, but HAB-exposed PbTx values were considerably lower relative to these other regions. Since no baseline STX dolphin data exist for any region, our data serve as a first step towards establishing reference STX values for potential dolphin mortality events associated with STX-producing blooms in the future. This study demonstrates that although HABs in eastern Florida are only infrequently associated with dolphin mortalities, the presence of toxins in these animals may pose significant health risks in this region.


Assuntos
Golfinho Nariz-de-Garrafa/metabolismo , Monitoramento Ambiental/métodos , Proliferação Nociva de Algas , Toxinas Marinhas/análise , Oxocinas/análise , Saxitoxina/análise , Poluentes Químicos da Água/análise , Animais , Dinoflagelados/crescimento & desenvolvimento , Ensaio de Imunoadsorção Enzimática , Florida , Fígado/química , Fígado/metabolismo , Toxinas Marinhas/toxicidade , Oxocinas/toxicidade , Rios/química , Saxitoxina/toxicidade , Poluentes Químicos da Água/toxicidade
3.
Int J Mol Sci ; 20(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640160

RESUMO

Tauopathy is a class of a neurodegenerative disorder linked with tau hyperphosphorylation, proteolysis, and aggregation. Tau can be subjected to proteolysis upon calpain activation in Alzheimer disease (AD), and traumatic brain injury (TBI). We and others have extensively researched calpain-mediated tau breakdown products (Tau-BDP; 45K, 35K, and 17K). Tau proteolysis might also generate low molecular weight (LMW ≤10K) proteolytic peptides after neurodegenerative damage. In this study, we have subjected purified tau protein (phospho and non-phospho) and mouse brain lysate to calpain-1 digestion to characterize the LMW generated by nano-liquid chromatography coupled to electrospray ionization to tandem mass spectrometry (nano-LC-ESI-MS/MS). We have also challenged differentiated primary cerebrocortical neuronal cultures (CTX) with neurotoxic agents (calcium ionophore calcimycin (A23187), staurosporine (STS), N-methyl-D-aspartate (NMDA), and Maitotoxin (MTX)) that mimic neurodegeneration to investigate the peptidome released into the conditioned cell media. We used a simple workflow in which we fractionate LMW calpain-mediated tau peptides by ultrafiltration (molecular weight cut-off value (MWCO) of 10K) and subject filtrate fractions to nano-LC-MS/MS analysis. The high molecular weight (HMW) peptides and intact proteins retained on the filter were analyzed separately by western blotting using total and phospho-specific tau antibodies. We have identified several novel proteolytic tau peptides (phosphorylated and non-phosphorylated) that are only present in samples treated with calpain or cell-based calpain activation model (particularly N- and C-terminal peptides). Our findings can help in developing future research strategies emphasizing on the suppression of tau proteolysis as a target.


Assuntos
Calpaína/metabolismo , Neurônios/citologia , Peptídeos/análise , Cultura Primária de Células/métodos , Proteínas tau/química , Animais , Calcimicina/toxicidade , Células Cultivadas , Cromatografia Líquida , Toxinas Marinhas/toxicidade , Camundongos , Camundongos Transgênicos , Peso Molecular , N-Metilaspartato/toxicidade , Nanotecnologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oxocinas/toxicidade , Fosforilação , Proteólise , Ratos , Espectrometria de Massas por Ionização por Electrospray , Estaurosporina/toxicidade , Espectrometria de Massas em Tandem
4.
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
5.
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
6.
Vopr Pitan ; 87(3): 18-29, 2018.
Artigo em Russo | MEDLINE | ID: mdl-30592876

RESUMO

Yessotoxin and its derivatives (about 90) are isolated from algae belonging to the species Protoceratium reticulatum, Gonyaulax cf. Spinifera, Lingulodinium polyedrum and from invertebrate organisms that feed on these algae. Previously yessotoxin have been associated with the group of diarrheal toxins. Later studies of the possible impact of yessotoxin on the activity of alkaline phosphatase allowed to exclude them from this group. Yessotoxin causes a violation of calcium entry in the cells, which, in turn, effects the calcium-calmodulin system and thus influences into homeostasis of the organism as a whole. It was shown that yessotoxin induces a biphasic change in the concentration of adenosine monophosphate, an initial increase with a subsequent relative decrease, within some minutes after adding the toxin to the lymphocytes cell culture. Yessotoxin has effects on immune system; which is manifested in an increase of cytokines level, by inducing the expression of the genes encoding them. Yessotoxin have impact into processes of cell adhesion via E-cadherin and, thus, could be an important factor in the development of Alzheimer's disease. It has been established that yessotoxin caused the development of apoptosis. In those cases all three mechanisms of cell death took place - apoptosis, paraptosis and autophagy. Yessotoxin's acute toxicity doses according to different data are from 100 to 500-750 µg per 1kg of body weight. Yessotoxin's acute reference dose (ARfD) - 25 µg/kg of body weight per day. The results of the analysis of yessotoxin level in shellfish meat showed that none of the studied samples contained more than 3.75 mg yessotoxin equivalents/kg shellfish meat. This level has been adopted by the European Union as the maximum acceptable level of yessotoxin in shellfish meat (EU Regulation N 786/2013). Presented data on the mechanism of action, toxicity and prevalence of yessotoxins make it necessary to establish regulations of their content in seafood, placed on the markets of the Eurasian Economic Union.


Assuntos
Inocuidade dos Alimentos , Oxocinas/toxicidade , Saúde Pública , Alimentos Marinhos/efeitos adversos , Alimentos Marinhos/análise , Animais , Humanos , Medição de Risco
7.
Mar Drugs ; 16(12)2018 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-30545061

RESUMO

Marine biotoxins in fish and shellfish can cause several symptoms in consumers, such as diarrhea, amnesia, or even death by paralysis. Monitoring programs are in place for testing shellfish on a regular basis. In some countries testing is performed using the so-called mouse bioassay, an assay that faces ethical concerns not only because of animal distress, but also because it lacks specificity and results in high amounts of false positives. In Europe, for lipophilic marine biotoxins (LMBs), a chemical analytical method using LC-MS/MS was developed as an alternative and is now the reference method. However, safety is often questioned when relying solely on such a method, and as a result, the mouse bioassay might still be used. In this study the use of a cell-based assay for screening, i.e., the neuro-2a assay, in combination with the official LC-MS/MS method was investigated as a new alternative strategy for the detection and quantification of LMBs. To this end, samples that had been tested previously with the mouse bioassay were analyzed in the neuro-2a bioassay and the LC-MS/MS method. The neuro-2a bioassay was able to detect all LMBs at the regulatory levels and all samples that tested positive in the mouse bioassay were also suspect in the neuro-2a bioassay. In most cases, these samples contained toxin levels (yessotoxins) that explain the outcome of the bioassay but did not exceed the established maximum permitted levels.


Assuntos
Alternativas aos Testes com Animais/métodos , Bioensaio/métodos , Toxinas Marinhas/análise , Intoxicação por Frutos do Mar/prevenção & controle , Frutos do Mar/análise , Alternativas aos Testes com Animais/instrumentação , Animais , Bioensaio/instrumentação , Bivalves , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Reações Falso-Positivas , Toxinas Marinhas/toxicidade , Camundongos , Oxocinas/análise , Oxocinas/toxicidade , Frutos do Mar/toxicidade , Intoxicação por Frutos do Mar/etiologia , Espectrometria de Massas em Tandem/instrumentação , Espectrometria de Massas em Tandem/métodos
8.
J Environ Radioact ; 192: 250-256, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29986316

RESUMO

Marine organisms are exposed to and affected by a multitude of chemicals present in seawater and can accumulate in their tissues a wide range of contaminants as well as natural biotoxins associated with harmful algal blooms (HABs). Trace elements and biotoxins may modify physiological functions in exposed organisms, and studies have been conducted to better understand their respective kinetics and effects in marine species. Despite the increasing concern of concurrent toxic HABs and pollution events due to anthropogenic pressures and global change, very little information is available on their combined effects. Chemical interactions between biotoxins and trace elements have been reported, and exposure to certain biotoxins is known to modify ion transport pathways, suggesting that biotoxins have the potential to alter trace element uptake. Using specific and sensitive radiotracer techniques (radioligand receptor binding assay and γ-spectrometry), this laboratory study examined the influence of pre-exposure to the brevetoxins (PbTxs)-producing microalgae Karenia brevis on the bioaccumulation of selected non-essential (Cd) and essential (Co, Mn and Zn) trace elements in the blue mussel Mytilus edulis. PbTxs are a group of neurotoxins known to accumulate in bivalves but also to have lethal effects on a number of marine organisms including fish and mammals. We found that, over 23 days exposure to the radiotracers, the bioaccumulation of the dissolved essential trace elements Co, Mn and Zn in M. edulis was not significantly affected by pre-exposure to toxic K. brevis. In contrast, the uptake rate constant ku of Cd was significantly higher in the pre-exposed group (p < 0.05), likely caused by a decrease in mussel clearance rates after K. brevis exposure. These results suggest that the effects of algal toxin exposure on bioaccumulation of trace elements in mussels may be trace element-dependent.


Assuntos
Monitoramento Ambiental , Toxinas Marinhas/toxicidade , Mytilus edulis/fisiologia , Oxocinas/toxicidade , Oligoelementos/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Mytilus edulis/efeitos dos fármacos , Mytilus edulis/metabolismo , Água do Mar/química , Poluentes Químicos da Água/metabolismo
9.
Aquat Toxicol ; 202: 153-162, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30031906

RESUMO

The Gulf of Mexico, including the southwest Florida coast, USA, experience recurrent blooms of the brevetoxin (PbTx)-producing dinoflagellate, Karenia brevis. Northern quahogs (hard clams) Mercenaria mercenaria, are an important commercial species in this region. This study examined the effects of field and laboratory exposure of adult clams to K. brevis during their reproductive period, and effects on their subsequently produced offspring. Ripe adult clams were collected from a site which had been exposed to an eight-month natural bloom of K. brevis and an unaffected reference site. Ripe adult clams were also exposed to bloom concentrations of K. brevis for 10 days in the laboratory. Clams exposed to K. brevis accumulated PbTx at concentrations of 1508 (field exposure), 1444 (1000 cells mL-1 laboratory treatment) and 5229 ng g-1 PbTx-3 eq (5000 cells mL-1 laboratory treatment). Field-exposed clams showed histopathological effects: a significantly higher prevalence of mucus in the stomach/ intestine (23.3%), edema in gill tissues (30%) and presence of the cestode parasite, Tylocephalum spp. in whole tissue (40%), compared to non-exposed clams (0, 3.3 and 6.7% respectively). These clams also showed reduced gonadal allocation (23% gonadal area) and a higher prevalence of clams of undetermined sex (20%) compared to those sampled from the non-exposed site (43% and 0%, respectively). It is hypothesized that less energy may be channeled into reproduction as more is allocated for homeostasis or tissue repair. The fertilization success of gametes obtained from both field and laboratory-exposed adults was significantly lower in clams that had been exposed to K. brevis and development of these offspring was negatively affected at Days 1 and 4 post-fertilization (in field- and laboratory-exposed clams at the higher K. brevis concentration and in laboratory-exposed clams at the higher K. brevis concentration, respectively). Negative effects may be due to toxin accumulation in the gametes of field-exposed clams (244 ± 50 ng PbTx g-1 and 470 ± 82 ng g-1 wet weight in oocytes and sperm, respectively). Adverse effects in M. mercenaria are compared to those previously reported in oysters, Crassostrea virginica, under similar conditions of exposure. This study provides further evidence of the impacts of K. brevis and its associated toxins on the adults and offspring of exposed shellfish. Site-selection for the collection of broodstock and aquaculture grow-out efforts should therefore consider the local occurrence of K. brevis blooms.


Assuntos
Dinoflagelados/metabolismo , Toxinas Marinhas/toxicidade , Mercenaria/crescimento & desenvolvimento , Oxocinas/toxicidade , Reprodução/efeitos dos fármacos , Animais , Cestoides/patogenicidade , Feminino , Células Germinativas/efeitos dos fármacos , Células Germinativas/crescimento & desenvolvimento , Brânquias/efeitos dos fármacos , Brânquias/patologia , Golfo do México , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/parasitologia , Masculino , Mercenaria/efeitos dos fármacos , Mercenaria/parasitologia , Muco/metabolismo , Estômago/efeitos dos fármacos , Estômago/patologia
10.
ACS Chem Neurosci ; 9(11): 2667-2678, 2018 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-29733572

RESUMO

Maitotoxins (MTX) are among the most potent marine toxins identified to date causing cell death trough massive calcium influx. However, the exact mechanism for the MTX-induced calcium entry and cytotoxicity is still unknown. In this work, the effect of MTX-1 on the cytosolic free calcium concentration and cellular viability of human neuronal stem cells was evaluated. MTX elicited a concentration-dependent decrease in cell viability which was already evident after 1 h of treatment with 0.25 nM MTX; however, at a concentration of 0.1 nM, the toxin did not cause cell death even after 14 days of exposure. Moreover, the toxin caused a concentration dependent rise in the cytosolic calcium concentration which was maximal at toxin concentrations of 1 nM and dependent on the presence of extracellular calcium on the bathing solution. Several pharmacological approaches were employed to evaluate the role of canonical transient potential receptor channels (TRPC) on the MTX effects. The results presented here lead to the identification of the TRPC4 channels as contributors to the MTX effects in human neuronal cells. Both, the calcium increase and the cytotoxicity of MTX were either fully (for the calcium increase) or partially (in the case of cytotoxicity) reverted by the blockade of canonical TRPC4 receptors with the selective antagonist ML204. Furthermore, the sodium proton exchanger blocker amiloride also partially inhibited the calcium rise and the cell death elicited by MTX while the combination of amiloride and ML204 fully prevented both the cytotoxicity and the calcium rise elicited by the toxin.


Assuntos
Amilorida/farmacologia , Cálcio/metabolismo , Morte Celular/efeitos dos fármacos , Indóis/farmacologia , Toxinas Marinhas/toxicidade , Células-Tronco Neurais/efeitos dos fármacos , Oxocinas/toxicidade , Piperidinas/farmacologia , Canais de Receptores Transientes de Potencial/antagonistas & inibidores , Bloqueadores do Canal Iônico Sensível a Ácido/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Células-Tronco Neurais/metabolismo
11.
Dis Aquat Organ ; 127(2): 145-150, 2018 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-29384484

RESUMO

Five green (Chelonia mydas) and 11 Kemp's ridley (Lepidochelys kempii) sea turtles found dead, or that died soon after stranding, on the southern Texas (USA) coast during 2 Karenia brevis blooms (October 2015, September-October 2016) were tested for exposure to brevetoxins (PbTx). Tissues (liver, kidney) and digesta (stomach and intestinal contents) were analyzed by ELISA. Three green turtles found alive during the 2015 event and 2 Kemp's ridley turtles found alive during the 2016 event exhibited signs of PbTx exposure, including lethargy and/or convulsions of the head and neck. PbTx were detected in 1 or more tissues or digesta in all 16 stranded turtles. Detected PbTx concentrations ranged from 2 to >2000 ng g-1. Necropsy examination and results of PbTx analysis indicated that 10 of the Kemp's ridleys and 2 of the green turtles died from brevetoxicosis via ingestion. This is the first documentation of sea turtle mortality in Texas attributed to brevetoxicosis.


Assuntos
Proliferação Nociva de Algas , Toxinas Marinhas/toxicidade , Micotoxicose/veterinária , Oxocinas/toxicidade , Tartarugas , Animais , Dinoflagelados , Micotoxicose/patologia , Texas
12.
Mar Drugs ; 16(1)2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29301247

RESUMO

Ciguatera Fish Poisoning (CFP) is a human illness caused by the consumption of marine fish contaminated with ciguatoxins (CTX) and possibly maitotoxins (MTX), produced by species from the benthic dinoflagellate genus Gambierdiscus. Here, we describe the identity and toxicology of Gambierdiscus spp. isolated from the tropical and temperate waters of eastern Australia. Based on newly cultured strains, we found that four Gambierdiscus species were present at the tropical location, including G. carpenteri, G. lapillus and two others which were not genetically identical to other currently described species within the genus, and may represent new species. Only G. carpenteri was identified from the temperate location. Using LC-MS/MS analysis we did not find any characterized microalgal CTXs (P-CTX-3B, P-CTX-3C, P-CTX-4A and P-CTX-4B) or MTX-1; however, putative maitotoxin-3 (MTX-3) was detected in all species except for the temperate population of G. carpenteri. Using the Ca2+ influx SH-SY5Y cell Fluorescent Imaging Plate Reader (FLIPR) bioassay we found CTX-like activity in extracts of the unidentified Gambierdiscus strains and trace level activity in strains of G. lapillus. While no detectable CTX-like activity was observed in tropical or temperate strains of G. carpenteri, all species showed strong maitotoxin-like activity. This study, which represents the most comprehensive analyses of the toxicology of Gambierdiscus strains isolated from Australia to date, suggests that CFP in this region may be caused by currently undescribed ciguatoxins and maitotoxins.


Assuntos
Ciguatoxinas/isolamento & purificação , Dinoflagelados/classificação , Toxinas Marinhas/isolamento & purificação , Oxocinas/isolamento & purificação , Animais , Austrália , Linhagem Celular Tumoral , Cromatografia Líquida/métodos , Intoxicação por Ciguatera , Ciguatoxinas/toxicidade , Dinoflagelados/química , Humanos , Toxinas Marinhas/toxicidade , Oxocinas/toxicidade , Espectrometria de Massas em Tandem , Clima Tropical
13.
Toxicon ; 149: 6-19, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29360534

RESUMO

Ciguatoxins (CTXs) and brevetoxins (PbTxs) are phycotoxins that can accumulate along the marine food chain and thus cause seafood poisoning in humans, namely "ciguatera fish poisoning" (CFP) and "neurotoxic shellfish poisoning" (NSP), respectively. CFP is characterized by early gastrointestinal symptoms and typical sensory disorders (paraesthesia, pain, pruritus and cold dysaesthesia), which can persist several weeks and, in some cases, several months or years. NSP is considered a mild form of CFP with similar but less severe symptoms. After inhaled exposure, PbTxs can also cause respiratory tract irritation in healthy subjects and asthma exacerbations in predisposed subjects, whose respiratory functions may be disrupted for several days following PbTx inhalation. Mechanistically, it is well established that CTX- or PbTx-induced disturbances are primarily mainly due to voltage-gated sodium channel activation in sensory and motor peripheral nervous system. However, little is known about the pathophysiology or a potential individual susceptibility to long lasting effects of CFP/NSP. In addition to their action on the nervous system, PbTxs and CTXs were also shown to exert effects on the immune system. However, their role in the pathophysiology of syndromes induced by CTX or PbTx exposure is poorly documented. The aim of this review is to inventory the literature thus far on the inflammatory and immune effects of PbTxs and CTXs.


Assuntos
Ciguatoxinas/toxicidade , Sistema Imunitário/efeitos dos fármacos , Toxinas Marinhas/toxicidade , Oxocinas/toxicidade , Humanos , Imunidade Inata/efeitos dos fármacos , Modelos Imunológicos , Canais de Sódio Disparados por Voltagem/efeitos dos fármacos
14.
J Wildl Dis ; 54(1): 142-146, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28829928

RESUMO

: On 16 September 2015, a red tide ( Karenia brevis) bloom impacted coastal areas of Padre Island National Seashore Park, Texas, US. Two days later and about 0.9 km inland, 30-40 adult green tree frogs ( Hyla cinerea) were found dead after displaying tremors, weakness, labored breathing, and other signs of neurologic impairment. A rainstorm accompanied by high winds, rough surf, and high tides, which could have aerosolized brevetoxin, occurred on the morning of the mortality event. Frog carcasses were in good body condition but contained significant brevetoxin in tissues. Tissue brevetoxin was also found in two dead or dying spotted ground squirrels ( Xerospermophilus spilosoma) and a coyote ( Canis latrans) found in the area. Rainwater collected from the location of the mortality event contained brevetoxin. Green tree frog and ground squirrel mortality has not been previously attributed to brevetoxin exposure and such mortality suggested that inland toxin transport, possibly through aerosols, rainfall, or insects, may have important implications for coastal species.


Assuntos
Anuros , Coiotes , Exposição Ambiental , Toxinas Marinhas/toxicidade , Micotoxicose/veterinária , Oxocinas/toxicidade , Sciuridae , Animais , Monitoramento Ambiental , Proliferação Nociva de Algas , Ilhas , Toxinas Marinhas/química , Micotoxicose/mortalidade , Oxocinas/química , Texas
15.
Mar Drugs ; 15(7)2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28665362

RESUMO

Ciguatoxins (CTXs), and possibly maitotoxins (MTXs), are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean). The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia), 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS), and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae, G. pacificus, G.honu, and F. paulensis) contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration.


Assuntos
Ciguatoxinas/toxicidade , Dinoflagelados/química , Toxinas Marinhas/toxicidade , Oxocinas/toxicidade , Administração Oral , Animais , Cromatografia Líquida , Intoxicação por Ciguatera/epidemiologia , Ciguatoxinas/administração & dosagem , Ciguatoxinas/isolamento & purificação , Feminino , Injeções Intraperitoneais , Toxinas Marinhas/administração & dosagem , Toxinas Marinhas/isolamento & purificação , Camundongos , Oxocinas/administração & dosagem , Oxocinas/isolamento & purificação , Oceano Pacífico , Especificidade da Espécie , Espectrometria de Massas em Tandem , Testes de Toxicidade
16.
Mar Drugs ; 15(7)2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28696398

RESUMO

Maitotoxins (MTXs) are among the most potent toxins known. These toxins are produced by epi-benthic dinoflagellates of the genera Gambierdiscus and Fukuyoa and may play a role in causing the symptoms associated with Ciguatera Fish Poisoning. A recent survey revealed that, of the species tested, the newly described species from the Canary Islands, G. excentricus, is one of the most maitotoxic. The goal of the present study was to characterize MTX-related compounds produced by this species. Initially, lysates of cells from two Canary Island G. excentricus strains VGO791 and VGO792 were partially purified by (i) liquid-liquid partitioning between dichloromethane and aqueous methanol followed by (ii) size-exclusion chromatography. Fractions from chromatographic separation were screened for MTX toxicity using both the neuroblastoma neuro-2a (N2a) cytotoxicity and Ca2+ flux functional assays. Fractions containing MTX activity were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to pinpoint potential MTX analogs. Subsequent non-targeted HRMS analysis permitted the identification of a novel MTX analog, maitotoxin-4 (MTX4, accurate mono-isotopic mass of 3292.4860 Da, as free acid form) in the most toxic fractions. HRMS/MS spectra of MTX4 as well as of MTX are presented. In addition, crude methanolic extracts of five other strains of G. excentricus and 37 other strains representing one Fukuyoa species and ten species, one ribotype and one undetermined strain/species of Gambierdiscus were screened for the presence of MTXs using low resolution tandem mass spectrometry (LRMS/MS). This targeted analysis indicated the original maitotoxin (MTX) was only present in one strain (G. australes S080911_1). Putative maitotoxin-2 (p-MTX2) and maitotoxin-3 (p-MTX3) were identified in several other species, but confirmation was not possible because of the lack of reference material. Maitotoxin-4 was detected in all seven strains of G. excentricus examined, independently of their origin (Brazil, Canary Islands and Caribbean), and not detected in any other species. MTX4 may therefore serve as a biomarker for the highly toxic G. excentricus in the Atlantic area.


Assuntos
Dinoflagelados/química , Toxinas Marinhas/química , Toxinas Marinhas/toxicidade , Oxocinas/química , Oxocinas/toxicidade , Animais , Bioensaio/métodos , Brasil , Região do Caribe , Linhagem Celular Tumoral , Intoxicação por Ciguatera/genética , Intoxicação por Ciguatera/parasitologia , Ciguatoxinas/toxicidade , Camundongos , Filogenia , Espanha , Especificidade da Espécie
17.
Sci Total Environ ; 605-606: 967-979, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28693110

RESUMO

Natural biotoxins and anthropogenic toxicants pose a significant risk to sea turtle health. Documented effects of contaminants include potential disease progression and adverse impacts on development, immune function, and survival in these imperiled species. The shallow seagrass habitats of Florida's northwest coast (Big Bend) serve as an important developmental habitat for Kemp's ridley (Lepidochelys kempii) and green (Chelonia mydas) sea turtles; however, few studies have been conducted in this area. Our objectives were (1) to evaluate plasma analytes (mass, minimum straight carapace length, body condition index [BCI], fibropapilloma tumor score, lysozyme, superoxide dismutase, reactive oxygen/nitrogen species, plasma protein electrophoresis, cholesterol, and total solids) in Kemp's ridleys and green turtles and their correlation to brevetoxins that were released from a red tide bloom event from July-October 2014 in the Gulf of Mexico near Florida's Big Bend, and (2) to analyze red blood cells in Kemp's ridleys and green turtles for toxic elements (arsenic, cadmium, lead, mercury, selenium, thallium) with correlation to the measured plasma analytes. Positive correlations were observed between brevetoxins and α2-globulins in Kemp's ridleys and α2- and γ-globulins in green turtles, indicating potential immunostimulation. Arsenic, cadmium, and lead positively correlated with superoxide dismutase in Kemp's ridleys, suggesting oxidative stress. Lead and mercury in green turtles negatively correlated with BCI, while mercury positively correlated with total tumor score of green turtles afflicted with fibropapillomatosis, suggesting a possible association with mercury and increased tumor growth. The total tumor score of green turtles positively correlated with total protein, total globulins, α2-globulins, and γ-globulins, further suggesting inflammation and immunomodulation as a result of fibropapillomatosis. Lastly, brevetoxin concentrations were positively related to tumor score, indicating potential tumor promotion by brevetoxin. These results signify that brevetoxins and toxic elements elicit various negative effects on sea turtle health, including immune function, oxidative stress, and possibly disease progression.


Assuntos
Proliferação Nociva de Algas , Toxinas Marinhas/toxicidade , Oxocinas/toxicidade , Tartarugas/sangue , Animais , Florida , Globulinas/análise , Golfo do México , Metais Pesados/sangue , Neoplasias/epidemiologia , Estresse Oxidativo
18.
Toxicol Appl Pharmacol ; 329: 58-66, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28551108

RESUMO

Karenia brevis, the Florida red tide dinoflagellate produces a suite of neurotoxins known as the brevetoxins. The most abundant of the brevetoxins PbTx-2, was found to inhibit the thioredoxin-thioredoxin reductase system, whereas the PbTx-3 has no effect on this system. On the other hand, PbTx-2 activates the reduction of small disulfides such as 5,5'-dithio-bis-(2-nitrobenzoic acid) by thioredoxin reductase. PbTx-2 has an α, ß-unsaturated aldehyde moiety which functions as an efficient electrophile and selenocysteine conjugates are readily formed. PbTx-2 blocks the inhibition of TrxR by the inhibitor curcumin, whereas curcumin blocks PbTx-2 activation of TrxR. It is proposed that the mechanism of inhibition of thioredoxin reduction is via the formation of a Michael adduct between selenocysteine and the α, ß-unsaturated aldehyde moiety of PbTx-2. PbTx-2 had no effect on the rates of reactions catalyzed by related enzymes such as glutathione reductase, glutathione peroxidase or glutaredoxin.


Assuntos
Inibidores Enzimáticos/toxicidade , Toxinas Marinhas/toxicidade , Oxocinas/toxicidade , Tiorredoxina Redutase 1/antagonistas & inibidores , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Relação Dose-Resposta a Droga , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Oxirredução , Domínios Proteicos , Ratos , Selenocisteína , Tiorredoxina Redutase 1/química , Tiorredoxina Redutase 1/metabolismo , Fatores de Tempo
19.
Harmful Algae ; 63: 173-183, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28366392

RESUMO

Species in the epi-benthic dinoflagellate genus Gambierdiscus produce ciguatoxins (CTXs) and maitotoxins (MTXs), which are among the most potent marine toxins known. Consumption of fish contaminated with sufficient quantities of CTXs causes Ciguatera Fish Poisoning (CFP), the largest cause of non-bacterial food poisoning worldwide. Maitotoxins, which can be found in the digestive system of fish, could also contribute to CFP if such tissues are consumed. Recently, an increasing number of Gambierdiscus species have been identified; yet, little is known about the variation in toxicity among Gambierdiscus strains or species. This study is the first assessment of relative CTX- and MTX-toxicity of Gambierdiscus species from areas as widespread as the North-Eastern Atlantic Ocean, Pacific Ocean and the Mediterranean Sea. A total of 13 strains were screened: (i) seven Pacific strains of G. australes, G. balechii, G. caribaeus, G. carpenteri, G. pacificus, G. scabrosus and one strain of an undetermined species (Gambierdiscus sp. Viet Nam), (ii) five strains from the North-Eastern Atlantic Ocean (two G. australes, a single G. excentricus and two G. silvae strains), and (iii) one G. carolinianus strain from the Mediterranean Sea. Cell pellets of Gambierdiscus were extracted with methanol and the crude extracts partitioned into a CTX-containing dichloromethane fraction and a MTX-containing aqueous methanol fraction. CTX-toxicity was estimated using the neuro-2a cytoxicity assay, and MTX-toxicity via a human erythrocyte lysis assay. Different species were grouped into different ratios of CTX- and MTX-toxicity, however, the ratio was not related to the geographical origin of species (Atlantic, Mediterranean, Pacific). All strains showed MTX-toxicity, ranging from 1.5 to 86pg MTX equivalents (eq) cell-1. All but one of the strains showed relatively low CTX-toxicity ranging from 0.6 to 50 fg CTX3C eq cell-1. The exception was the highly toxic G. excentricus strain from the Canary Islands, which produced 1426 fg CTX3C eq cell-1. As was true for CTX, the highest MTX-toxicity was also found in G. excentricus. Thus, the present study confirmed that at least one species from the Atlantic Ocean demonstrates similar toxicity as the most toxic strains from the Pacific, even if the metabolites in fish have so far been shown to be more toxic in the Pacific Ocean.


Assuntos
Bioensaio/métodos , Dinoflagelados/metabolismo , Toxinas Marinhas/análise , Animais , Intoxicação por Ciguatera , Ciguatoxinas/análise , Ciguatoxinas/toxicidade , Eritrócitos/efeitos dos fármacos , Toxinas Marinhas/toxicidade , Oxocinas/análise , Oxocinas/toxicidade , Filogenia
20.
Aquat Toxicol ; 187: 29-37, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28363127

RESUMO

Harmful algal blooms (HABs) occur nearly annually off the west coast of Florida and can impact both humans and wildlife, resulting in morbidity and increased mortality of marine animals including sea turtles. The key organism in Florida red tides is the dinoflagellate Karenia brevis that produces a suite of potent neurotoxins referred to as the brevetoxins (PbTx). Despite recent mortality events and rehabilitation efforts, still little is known about how the toxin directly impacts sea turtles, as they are not amenable to experimentation and what is known about toxin levels and distribution comes primarily from post-mortem data. In this study, we utilized the freshwater turtle Trachemys scripta and the diamondback terrapin, Malaclemys terrapin as model organisms to determine the distribution, clearance, and routes of excretion of the most common form of the toxin, brevetoxin-3, in turtles. Turtles were administered toxin via esophageal tube to mimic ingestion (33.48µg/kg PbTx-3, 3×/week for two weeks for a total of 7 doses) or by intratracheal instillation (10.53µg/kg, 3×/week for four weeks for a total of 12 doses) to mimic inhalation. Both oral and intratracheal administration of the toxin produced a suite of behavioral responses symptomatic of brevetoxicosis. The toxin distributed to all organ systems within 1h of administration but was rapidly cleared out over 24-48h, corresponding to a decline in clinical symptoms. Excretion appears to be primarily through conjugation to bile salts. Histopathological study revealed that the frequency of lesions varied within experimental groups with some turtles having no significant lesions at all, while similar lesions were found in a low number of control turtles suggesting another common factor(s) could be responsible. The overall goal of this research is better understand the impacts of brevetoxin on turtles in order to develop better treatment protocols for sea turtles exposed to HABs.


Assuntos
Toxinas Marinhas/farmacocinética , Neurotoxinas/farmacocinética , Oxocinas/farmacocinética , Tartarugas/metabolismo , Poluentes Químicos da Água/farmacocinética , Administração Oral , Animais , Comportamento Animal/efeitos dos fármacos , Dinoflagelados/metabolismo , Feminino , Florida , Água Doce/química , Proliferação Nociva de Algas , Humanos , Exposição por Inalação , Masculino , Toxinas Marinhas/toxicidade , Taxa de Depuração Metabólica , Modelos Biológicos , Neurotoxinas/toxicidade , Especificidade de Órgãos , Oxocinas/toxicidade , Distribuição Tecidual , Poluentes Químicos da Água/toxicidade
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