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1121 KiB

Open AccessArticle

Occurrence of Lipophilic Marine Toxins in Shellfish from Galicia (NW of Spain) and Synergies among Them

by Laura P. Rodríguez, Virginia González, Aníbal Martínez, Beatriz Paz, Jorge Lago, Victoria Cordeiro, Lucía Blanco, Juan Manuel Vieites and Ana G. Cabado

Mar. Drugs 2015, 13(4), 1666-1687; https://doi.org/10.3390/md13041666 - 25 Mar 2015

Cited by 22 | Viewed by 7277

Abstract

Lipophilic marine toxins pose a serious threat for consumers and an enormous economic problem for shellfish producers. Synergistic interaction among toxins may play an important role in the toxicity of shellfish and consequently in human intoxications. In order to study the toxic profile [...] Read more.

Lipophilic marine toxins pose a serious threat for consumers and an enormous economic problem for shellfish producers. Synergistic interaction among toxins may play an important role in the toxicity of shellfish and consequently in human intoxications. In order to study the toxic profile of molluscs, sampled during toxic episodes occurring in different locations in Galicia in 2014, shellfish were analyzed by liquid chromatography tandem mass spectrometry (LC–MS/MS), the official method for the detection of lipophilic toxins. The performance of this procedure was demonstrated to be fit for purpose and was validated in house following European guidelines. The vast majority of toxins present in shellfish belonged to the okadaic acid (OA) group and some samples from a particular area contained yessotoxin (YTX). Since these toxins occur very often with other lipophilic toxins, we evaluated the potential interactions among them. A human neuroblastoma cell line was used to study the possible synergies of OA with other lipophilic toxins. Results show that combination of OA with dinophysistoxin 2 (DTX2) or YTX enhances the toxicity triggered by OA, decreasing cell viability and cell proliferation, depending on the toxin concentration and incubation time. The effects of other lipophilic toxins as 13-desmethyl Spirolide C were also evaluated in vitro. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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531 KiB

Open AccessArticle

6-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda crassicornis is an Agonist of Human α7 Nicotinic Acetylcholine Receptor

by Igor E. Kasheverov, Irina V. Shelukhina, Denis S. Kudryavtsev, Tatyana N. Makarieva, Ekaterina N. Spirova, Alla G. Guzii, Valentin A. Stonik and Victor I. Tsetlin

Mar. Drugs 2015, 13(3), 1255-1266; https://doi.org/10.3390/md13031255 - 12 Mar 2015

Cited by 25 | Viewed by 8039

Abstract

6-Bromohypaphorine (6-BHP) has been isolated from the marine sponges Pachymatisma johnstoni, Aplysina sp., and the tunicate Aplidium conicum, but data on its biological activity were not available. For the nudibranch mollusk Hermissenda crassicornis no endogenous compounds were known, and [...] Read more.

6-Bromohypaphorine (6-BHP) has been isolated from the marine sponges Pachymatisma johnstoni, Aplysina sp., and the tunicate Aplidium conicum, but data on its biological activity were not available. For the nudibranch mollusk Hermissenda crassicornis no endogenous compounds were known, and here we describe the isolation of 6-BHP from this mollusk and its effects on different nicotinic acetylcholine receptors (nAChR). Two-electrode voltage-clamp experiments on the chimeric α7 nAChR (built of chicken α7 ligand-binding and glycine receptor transmembrane domains) or on rat α4β2 nAChR expressed in Xenopus oocytes revealed no action of 6-BHP. However, in radioligand analysis, 6-BHP competed with radioiodinated α-bungarotoxin for binding to human α7 nAChR expressed in GH₄C₁ cells (IC₅₀ 23 ± 1 μM), but showed no competition on muscle-type nAChR from Torpedo californica. In Ca²⁺-imaging experiments on the human α7 nAChR expressed in the Neuro2a cells, 6-BHP in the presence of PNU120596 behaved as an agonist (EC₅₀ ~80 μM). To the best of our knowledge, 6-BHP is the first low-molecular weight compound from marine source which is an agonist of the nAChR subtype. This may have physiological importance because H. crassicornis, with its simple and tractable nervous system, is a convenient model system for studying the learning and memory processes. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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1071 KiB

Open AccessArticle

Involvement of JNK and Caspase Activation in Hoiamide A-Induced Neurotoxicity in Neocortical Neurons

by Zhengyu Cao, Xichun Li, Xiaohan Zou, Michael Greenwood, William H. Gerwick and Thomas F. Murray

Mar. Drugs 2015, 13(2), 903-919; https://doi.org/10.3390/md13020903 - 10 Feb 2015

Cited by 14 | Viewed by 6860

Abstract

The frequent occurrence of Moorea producens (formerly Lyngbya majuscula) blooms has been associated with adverse effects on human health. Hoiamide A is a structurally unique cyclic depsipeptide isolated from an assemblage of the marine cyanobacteria M. producens and Phormidium gracile. [...] Read more.

The frequent occurrence of Moorea producens (formerly Lyngbya majuscula) blooms has been associated with adverse effects on human health. Hoiamide A is a structurally unique cyclic depsipeptide isolated from an assemblage of the marine cyanobacteria M. producens and Phormidium gracile. We examined the influence of hoiamide A on neurite outgrowth in neocortical neurons and found that it suppressed neurite outgrowth with an IC₅₀ value of 4.89 nM. Further study demonstrated that hoiamide A stimulated lactic acid dehydrogenase (LDH) efflux, nuclear condensation and caspase-3 activity with EC₅₀ values of 3.66, 2.55 and 4.33 nM, respectively. These data indicated that hoiamide A triggered a unique neuronal death profile that involves both necrotic and apoptotic mechanisms. The similar potencies and similar time-response relationships between LDH efflux and caspase-3 activation/nuclear condensation suggested that both necrosis and apoptosis may derive from interaction with a common molecular target. The broad-spectrum caspase inhibitor, Z-VAD-FMK completely inhibited hoiamide A-induced neurotoxicity. Additionally, hoiamide A stimulated JNK phosphorylation, and a JNK inhibitor attenuated hoiamide A-induced neurotoxicity. Collectively, these data demonstrate that hoiamide A-induced neuronal death requires both JNK and caspase signaling pathways. The potent neurotoxicity and unique neuronal cell death profile of hoiamide A represents a novel neurotoxic chemotype from marine cyanobacteria. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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Open AccessArticle

Intracellular Immunohistochemical Detection of Tetrodotoxin in Pleurobranchaea maculata (Gastropoda) and Stylochoplana sp. (Turbellaria)

by Lauren R. Salvitti, Susanna A. Wood, Leigh Winsor and Stephen Craig Cary

Mar. Drugs 2015, 13(2), 756-769; https://doi.org/10.3390/md13020756 - 28 Jan 2015

Cited by 29 | Viewed by 7677

Abstract

Tetrodotoxin (TTX), is a potent neurotoxin targeting sodium channels that has been identified in multiple marine and terrestrial organisms. It was recently detected in the Opisthobranch Pleurobranchaea maculata and a Platyhelminthes Stylochoplana sp. from New Zealand. Knowledge on the distribution of TTX within [...] Read more.

Tetrodotoxin (TTX), is a potent neurotoxin targeting sodium channels that has been identified in multiple marine and terrestrial organisms. It was recently detected in the Opisthobranch Pleurobranchaea maculata and a Platyhelminthes Stylochoplana sp. from New Zealand. Knowledge on the distribution of TTX within these organisms is important to assist in elucidating the origin and ecological role of this toxin. Intracellular micro-distribution of TTX was investigated using a monoclonal antibody-based immunoenzymatic technique. Tetrodotoxin was strongly localized in neutral mucin cells and the basement membrane of the mantle, the oocytes and follicles of the gonad tissue, and in the digestive tissue of P. maculata. The ova and pharynx were the only two structures to contain TTX in Stylochoplana sp. Using liquid chromatography-mass spectrometry, TTX was identified in the larvae and eggs, but not the gelatinous egg cases of P. maculata. Tetrodotoxin was present in egg masses of Stylochoplana sp. These data suggest that TTX has a defensive function in adult P. maculata, who then invest this in their progeny for protection. Localization in the digestive tissue of P. maculata potentially indicates a dietary source of TTX. Stylochoplana sp. may use TTX in prey capture and for the protection of offspring. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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538 KiB

Open AccessFeature PaperCommunication

Augmenting Anti-Cancer Natural Products with a Small Molecule Adjuvant

by Paul G. Wahome, Kevin R. Beauchesne, Anna C. Pedone, John Cavanagh, Christian Melander, Paul Zimba and Peter D. R. Moeller

Mar. Drugs 2015, 13(1), 65-75; https://doi.org/10.3390/md13010065 - 26 Dec 2014

Cited by 12 | Viewed by 6989

Abstract

Aquatic microbes produce diverse secondary metabolites with interesting biological activities. Cytotoxic metabolites have the potential to become lead compounds or drugs for cancer treatment. Many cytotoxic compounds, however, show undesirable toxicity at higher concentrations. Such undesirable activity may be reduced or eliminated by [...] Read more.

Aquatic microbes produce diverse secondary metabolites with interesting biological activities. Cytotoxic metabolites have the potential to become lead compounds or drugs for cancer treatment. Many cytotoxic compounds, however, show undesirable toxicity at higher concentrations. Such undesirable activity may be reduced or eliminated by using lower doses of the cytotoxic compound in combination with another compound that modulates its activity. Here, we have examined the cytotoxicity of four microbial metabolites [ethyl N-(2-phenethyl) carbamate (NP-1), Euglenophycin, Anabaenopeptin, and Glycolipid 652] using three in vitro cell lines [human breast cancer cells (MCF-7), mouse neuroblastoma cells (N2a), and rat pituitary epithelial cells (GH4C1)]. The compounds showed variable cytotoxicity, with Euglenophycin displaying specificity for N2a cells. We have also examined the modulatory power of NP-1 on the cytotoxicity of the other three compounds and found that at a permissible concentration (125 µg/mL), NP-1 sensitized N2a and MCF-7 cells to Euglenophycin and Glycolipid 652 induced cytotoxicity. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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1154 KiB

Open AccessArticle

Beta-N-Methylamino-l-Alanine: LC-MS/MS Optimization, Screening of Cyanobacterial Strains and Occurrence in Shellfish from Thau, a French Mediterranean Lagoon

by Damien Réveillon, Eric Abadie, Véronique Séchet, Luc Brient, Véronique Savar, Michèle Bardouil, Philipp Hess and Zouher Amzil

Mar. Drugs 2014, 12(11), 5441-5467; https://doi.org/10.3390/md12115441 - 17 Nov 2014

Cited by 59 | Viewed by 9112

Abstract

β-N-methylamino-l-alanine (BMAA) is a neurotoxic non-protein amino acid suggested to be involved in neurodegenerative diseases. It was reported to be produced by cyanobacteria, but also found in edible aquatic organisms, thus raising concern of a widespread human exposure. However, the chemical [...] Read more.

β-N-methylamino-l-alanine (BMAA) is a neurotoxic non-protein amino acid suggested to be involved in neurodegenerative diseases. It was reported to be produced by cyanobacteria, but also found in edible aquatic organisms, thus raising concern of a widespread human exposure. However, the chemical analysis of BMAA and its isomers are controversial, mainly due to the lack of selectivity of the analytical methods. Using factorial design, we have optimized the chromatographic separation of underivatized analogues by a hydrophilic interaction chromatography coupled to tandem mass spectrometry (HILIC-MS/MS) method. A combination of an effective solid phase extraction (SPE) clean-up, appropriate chromatographic resolution and the use of specific mass spectral transitions allowed for the development of a highly selective and sensitive analytical procedure to identify and quantify BMAA and its isomers (in both free and total form) in cyanobacteria and mollusk matrices (LOQ of 0.225 and 0.15 µg/g dry weight, respectively). Ten species of cyanobacteria (six are reported to be BMAA producers) were screened with this method, and neither free nor bound BMAA could be found, while both free and bound DAB were present in almost all samples. Mussels and oysters collected in 2009 in the Thau Lagoon, France, were also screened, and bound BMAA and its two isomers, DAB and AEG, were observed in all samples (from 0.6 to 14.4 µg/g DW), while only several samples contained quantifiable free BMAA. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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891 KiB

Open AccessArticle

Endotoxin Structures in the Psychrophiles Psychromonas marina and Psychrobacter cryohalolentis Contain Distinctive Acyl Features

by Charles R. Sweet, Giancarlo M. Alpuche, Corinne A. Landis and Benjamin C. Sandman

Mar. Drugs 2014, 12(7), 4126-4147; https://doi.org/10.3390/md12074126 - 9 Jul 2014

Cited by 14 | Viewed by 7743

Abstract

Lipid A is the essential component of endotoxin (Gram-negative lipopolysaccharide), a potent immunostimulatory compound. As the outer surface of the outer membrane, the details of lipid A structure are crucial not only to bacterial pathogenesis but also to membrane integrity. This work characterizes [...] Read more.

Lipid A is the essential component of endotoxin (Gram-negative lipopolysaccharide), a potent immunostimulatory compound. As the outer surface of the outer membrane, the details of lipid A structure are crucial not only to bacterial pathogenesis but also to membrane integrity. This work characterizes the structure of lipid A in two psychrophiles, Psychromonas marina and Psychrobacter cryohalolentis, and also two mesophiles to which they are related using MALDI-TOF MS and fatty acid methyl ester (FAME) GC-MS. P. marina lipid A is strikingly similar to that of Escherichia coli in organization and total acyl size, but incorporates an unusual doubly unsaturated tetradecadienoyl acyl residue. P. cryohalolentis also shows structural organization similar to a closely related mesophile, Acinetobacter baumannii, however it has generally shorter acyl constituents and shows many acyl variants differing by single methylene (-CH₂-) units, a characteristic it shares with the one previously reported psychrotolerant lipid A structure. This work is the first detailed structural characterization of lipid A from an obligate psychrophile and the second from a psychrotolerant species. It reveals distinctive structural features of psychrophilic lipid A in comparison to that of related mesophiles which suggest constitutive adaptations to maintain outer membrane fluidity in cold environments. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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1011 KiB

Open AccessArticle

Confirmation of Pinnatoxins and Spirolides in Shellfish and Passive Samplers from Catalonia (Spain) by Liquid Chromatography Coupled with Triple Quadrupole and High-Resolution Hybrid Tandem Mass Spectrometry

by María García-Altares, Alexis Casanova, Vaishali Bane, Jorge Diogène, Ambrose Furey and Pablo De la Iglesia

Mar. Drugs 2014, 12(6), 3706-3732; https://doi.org/10.3390/md12063706 - 23 Jun 2014

Cited by 71 | Viewed by 7510

Abstract

Cyclic imines are lipophilic marine toxins that bioaccumulate in seafood. Their structure comprises a cyclic-imino moiety, responsible for acute neurotoxicity in mice. Cyclic imines have not been linked yet to human poisonings and are not regulated in Europe, although the European Food Safety [...] Read more.

Cyclic imines are lipophilic marine toxins that bioaccumulate in seafood. Their structure comprises a cyclic-imino moiety, responsible for acute neurotoxicity in mice. Cyclic imines have not been linked yet to human poisonings and are not regulated in Europe, although the European Food Safety Authority requires more data to perform a conclusive risk assessment for consumers. This work presents the first detection of pinnatoxin G (PnTX-G) in Spain and 13-desmethyl spirolide C (SPX-1) in shellfish from Catalonia (Spain, NW Mediterranean Sea). Cyclic imines were found at low concentrations (2 to 60 µg/kg) in 13 samples of mussels and oysters (22 samples analyzed). Pinnatoxin G has been also detected in 17 seawater samples (out of 34) using solid phase adsorption toxin tracking devices (0.3 to 0.9 µg/kg-resin). Pinnatoxin G and SPX-1 were confirmed with both low and high resolution (<2 ppm) mass spectrometry by comparison of the response with that from reference standards. For other analogs without reference standards, we applied a strategy combining low resolution MS with a triple quadrupole mass analyzer for a fast and reliable screening, and high resolution MS LTQ Orbitrap^® for unambiguous confirmation. The advantages and limitations of using high resolution MS without reference standards were discussed. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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Review

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424 KiB

Open AccessReview

Potential Threats Posed by Tetrodotoxins in UK Waters: Examination of Detection Methodology Used in Their Control

by Andrew D. Turner, Cowan Higgins, Wendy Higman and James Hungerford

Mar. Drugs 2015, 13(12), 7357-7376; https://doi.org/10.3390/md13127070 - 11 Dec 2015

Cited by 29 | Viewed by 7872

Abstract

Tetrodotoxin is a neurotoxin responsible for many human fatalities, most commonly following the consumption of pufferfish. Whilst the source of the toxin has not been conclusively proven, it is thought to be associated with various species of marine bacteria. Whilst the toxins are [...] Read more.

Tetrodotoxin is a neurotoxin responsible for many human fatalities, most commonly following the consumption of pufferfish. Whilst the source of the toxin has not been conclusively proven, it is thought to be associated with various species of marine bacteria. Whilst the toxins are well studied in fish and gastropods, in recent years, there have been a number of reports of tetrodotoxin occurring in bivalve shellfish, including those harvested from the UK and other parts of Europe. This paper reviews evidence concerning the prevalence of tetrodotoxins in the UK together with methodologies currently available for testing. Biological, biomolecular and chemical methods are reviewed, including recommendations for further work. With the recent development of quantitative chromatographic methods for these and other hydrophilic toxins, as well as the commercial availability of rapid testing kits, there are a number of options available to ensure consumers are protected against this threat. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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Open AccessReview

Potential Threats Posed by New or Emerging Marine Biotoxins in UK Waters and Examination of Detection Methodologies Used for Their Control: Cyclic Imines

by Keith Davidson, Clothilde Baker, Cowan Higgins, Wendy Higman, Sarah Swan, Andrea Veszelovszki and Andrew D. Turner

Mar. Drugs 2015, 13(12), 7087-7112; https://doi.org/10.3390/md13127057 - 26 Nov 2015

Cited by 38 | Viewed by 6570

Abstract

Cyclic imines (CIs) are a group of phytoplankton produced toxins related to shellfish food products, some of which are already present in UK and European waters. Their risk to shellfish consumers is poorly understood, as while no human intoxication has been definitively related [...] Read more.

Cyclic imines (CIs) are a group of phytoplankton produced toxins related to shellfish food products, some of which are already present in UK and European waters. Their risk to shellfish consumers is poorly understood, as while no human intoxication has been definitively related to this group, their fast acting toxicity following intraperitoneal injection in mice has led to concern over their human health implications. A request was therefore made by UK food safety authorities to examine these toxins more closely to aid possible management strategies. Of the CI producers only the spirolide producer Alexandrium ostenfeldii is known to exist in UK waters at present but trends in climate change may lead to increased risk from other organisms/CI toxins currently present elsewhere in Europe and in similar environments worldwide. This paper reviews evidence concerning the prevalence of CIs and CI-producing phytoplankton, together with testing methodologies. Chemical, biological and biomolecular methods are reviewed, including recommendations for further work to enable effective testing. Although the focus here is on the UK, from a strategic standpoint many of the topics discussed will also be of interest in other parts of the world since new and emerging marine biotoxins are of global concern. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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Open AccessReview

Toxic Picoplanktonic Cyanobacteria—Review

by Natalia Jakubowska and Elżbieta Szeląg-Wasielewska

Mar. Drugs 2015, 13(3), 1497-1518; https://doi.org/10.3390/md13031497 - 18 Mar 2015

Cited by 86 | Viewed by 10266

Abstract

Cyanobacteria of a picoplanktonic cell size (0.2 to 2.0 µm) are common organisms of both freshwater and marine ecosystems. However, due to their small size and relatively short study history, picoplanktonic cyanobacteria, in contrast to the microplanktonic cyanobacteria, still remains a poorly studied [...] Read more.

Cyanobacteria of a picoplanktonic cell size (0.2 to 2.0 µm) are common organisms of both freshwater and marine ecosystems. However, due to their small size and relatively short study history, picoplanktonic cyanobacteria, in contrast to the microplanktonic cyanobacteria, still remains a poorly studied fraction of plankton. So far, only little information on picocyanobacteria toxicity has been reported, while the number of reports concerning their presence in ecosystems is increasing. Thus, the issue of picocyanobacteria toxicity needs more researchers’ attention and interest. In this report, we present information on the current knowledge concerning the picocyanobacteria toxicity, as well as their harmfulness and problems they can cause. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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Open AccessReview

Potential Threats Posed by New or Emerging Marine Biotoxins in UK Waters and Examination of Detection Methodology Used in Their Control: Brevetoxins

by Andrew D. Turner, Cowan Higgins, Keith Davidson, Andrea Veszelovszki, Daniel Payne, James Hungerford and Wendy Higman

Mar. Drugs 2015, 13(3), 1224-1254; https://doi.org/10.3390/md13031224 - 12 Mar 2015

Cited by 39 | Viewed by 8685

Abstract

Regular occurrence of brevetoxin-producing toxic phytoplankton in commercial shellfishery areas poses a significant risk to shellfish consumer health. Brevetoxins and their causative toxic phytoplankton are more limited in their global distribution than most marine toxins impacting commercial shellfisheries. On the other hand, trends [...] Read more.

Regular occurrence of brevetoxin-producing toxic phytoplankton in commercial shellfishery areas poses a significant risk to shellfish consumer health. Brevetoxins and their causative toxic phytoplankton are more limited in their global distribution than most marine toxins impacting commercial shellfisheries. On the other hand, trends in climate change could conceivably lead to increased risk posed by these toxins in UK waters. A request was made by UK food safety authorities to examine these toxins more closely to aid possible management strategies, should they pose a threat in the future. At the time of writing, brevetoxins have been detected in the Gulf of Mexico, the Southeast US coast and in New Zealand waters, where regulatory levels for brevetoxins in shellfish have existed for some time. This paper reviews evidence concerning the prevalence of brevetoxins and brevetoxin-producing phytoplankton in the UK, together with testing methodologies. Chemical, biological and biomolecular methods are reviewed, including recommendations for further work to enable effective testing. Although the focus here is on the UK, from a strategic standpoint many of the topics discussed will also be of interest in other parts of the world since new and emerging marine biotoxins are of global concern. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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Open AccessReview

Emergence and Epidemiology of Ciguatera in the Coastal Cities of Southern China

by Thomas Y. K. Chan

Mar. Drugs 2015, 13(3), 1175-1184; https://doi.org/10.3390/md13031175 - 2 Mar 2015

Cited by 14 | Viewed by 7661

Abstract

In the present review of 23 published case studies, the main objective is to report the emergence and epidemiology of ciguatera in the coastal cities of southern China. There was a sudden surge in ciguatera outbreaks in 2004. Ciguatera mostly occurred in the [...] Read more.

In the present review of 23 published case studies, the main objective is to report the emergence and epidemiology of ciguatera in the coastal cities of southern China. There was a sudden surge in ciguatera outbreaks in 2004. Ciguatera mostly occurred in the Guangdong Province. In Shenzhen, the incidence of ciguatera in 2004 was estimated to be over 7.5 per million people. In Foshan and Zhongshan, three large outbreaks each affecting over 100–200 subjects (caused by tiger grouper served at banquets) accounted for the much higher incidence of ciguatera in 2004 (>48.7 and >129.9 per million people). Humphead wrasse and areolated coral grouper were the other important ciguatoxic fish. In some subjects, risk factors for increased likelihood of (severe) ciguatera were present, namely concomitant alcohol consumption and ingestion of large reef fishes and CTX-rich fish parts. To prevent large outbreaks and severe illness, large apex predators from coral reefs should never be served at banquets and the public should realize the increased risk of severe symptoms due to ingestion of CTX-rich fish parts with alcohol. The systematic collection of accurate details, implementation of risk assessment process and continuing education for the public on prevention are of obvious importance. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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Open AccessReview

Selective Blocking Effects of 4,9-Anhydrotetrodotoxin, Purified from a Crude Mixture of Tetrodotoxin Analogues, on Na_V1.6 Channels and Its Chemical Aspects

by Noriyoshi Teramoto and Mari Yotsu-Yamashita

Mar. Drugs 2015, 13(2), 984-995; https://doi.org/10.3390/md13020984 - 12 Feb 2015

Cited by 14 | Viewed by 7141

Abstract

Tetrodotoxin (TTX) is a potent neurotoxin found in a number of marine creatures including the pufferfish, where it is synthesized by bacteria and accumulated through the food chain. It is a potent and selective blocker of some types of voltage-gated Na⁺ channel [...] Read more.

Tetrodotoxin (TTX) is a potent neurotoxin found in a number of marine creatures including the pufferfish, where it is synthesized by bacteria and accumulated through the food chain. It is a potent and selective blocker of some types of voltage-gated Na⁺ channel (Na_V channel). 4,9-Anhydrotetrodotoxin (4,9-anhydroTTX) was purified from a crude mixture of TTX analogues (such as TTX, 4-epiTTX, 6-epiTTX, 11-oxoTTX and 11-deoxyTTX) by the use of liquid chromatography-fluorescence detection (LC-FLD) techniques. Recently, it has been reported that 4,9-anhydroTTX selectively blocks the activity of Na_V1.6 channels with a blocking efficacy 40–160 times higher than that for other TTX-sensitive Na_V1.x channel isoforms. However, little attention has been paid to the molecular properties of the α-subunit in Na_V1.6 channels and the characteristics of binding of 4,9-anhydroTTX. From a functional point of view, it is important to determine the relative expression of Na_V1.6 channels in a wide variety of tissues. The aim of this review is to discuss briefly current knowledge about the pharmacology of 4,9-anhydroTTX, and provide an analysis of the molecular structure of native Na_V1.6 channels. In addition, chemical aspects of 4,9-anhydroTTX are briefly covered. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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Open AccessReview

Alternative Methods for the Detection of Emerging Marine Toxins: Biosensors, Biochemical Assays and Cell-Based Assays

by Laia Reverté, Lucía Soliño, Olga Carnicer, Jorge Diogène and Mònica Campàs

Mar. Drugs 2014, 12(12), 5719-5763; https://doi.org/10.3390/md12125719 - 26 Nov 2014

Cited by 78 | Viewed by 8864

Abstract

The emergence of marine toxins in water and seafood may have a considerable impact on public health. Although the tendency in Europe is to consolidate, when possible, official reference methods based on instrumental analysis, the development of alternative or complementary methods providing functional [...] Read more.

The emergence of marine toxins in water and seafood may have a considerable impact on public health. Although the tendency in Europe is to consolidate, when possible, official reference methods based on instrumental analysis, the development of alternative or complementary methods providing functional or toxicological information may provide advantages in terms of risk identification, but also low cost, simplicity, ease of use and high-throughput analysis. This article gives an overview of the immunoassays, cell-based assays, receptor-binding assays and biosensors that have been developed for the screening and quantification of emerging marine toxins: palytoxins, ciguatoxins, cyclic imines and tetrodotoxins. Their advantages and limitations are discussed, as well as their possible integration in research and monitoring programs. Full article

(This article belongs to the Special Issue Emerging Marine Toxins)

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