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Tetrodotoxins
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Tetrodotoxins

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Marine and Freshwater Toxins".

Deadline for manuscript submissions: closed (30 April 2019) | Viewed by 34349

Special Issue Editor

Dr. Panagiota Katikou

E-Mail Website
Guest Editor
Hellenic Agricultural Organization—DIMITRA, Veterinary Research Institute of Thessaloniki, Department of Hy-giene and Technology of Food of Animal Origin and Toxicology, 57001 Thermi, Greece
Interests: marine biotoxins; phycotoxins; harmful algal blooms; toxic pufferfish; emerging marine toxins; tetrodotoxins; ciguatoxins; lipophilic toxins; toxic episodes management; phycotoxins regulatory monitoring; marine toxins analysis; mouse bioassay; liquid chromatography mass spectrometry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tetrodotoxin (TTX) is one of the most potent naturally-occuring neurotoxins, responsible for many human intoxications and fatalities. The recent occurences of TTX and its analogues (TTXs) in edible aquatic organisms, such as marine gastropods and bivalve molluscs, as well as in new latitudes, has raised concerns in Europe about the necessity to regulate this group of toxins in order to protect human health. In this context, further investigations regarding TTXs presence and origin in aquatic environments, development of more sophisticated analysis methods, further data on human intoxication incidents and toxicological potency of TTX and its analogues are considered extremely important and necessary.

This Special Issue aims to focus on new information and scientific evidence mainly with regard to: (i) TTXs occurrence in aquatic environments, with an emphasis on edible aquatic organisms; (ii) analysis methods for the determination of TTXs; (iii) advances in the clarification of TTX producing organisms, (iv) environmental factors involved in the presence of TTXs and (v) assessment of public health risks related to the presence of TTXs, as well as risk management and mitigation strategies. Studies addressing any other questions of relevance related to TTXs would also be considered of interest and are also welcome to be submitted.

Dr. Panagiota Katikou
Guest Editor

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Keywords

  • Tetrodotoxin
  • aquatic organisms
  • bivalve mollusks
  • pufferfish
  • climate change
  • tetrodotoxin-producing bacteria
  • mouse bioassay
  • liquid chromatography-mass spectrometry
  • human poisoning
  • tetrodotoxin analogues

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Published Papers (7 papers)

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Research

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9 pages, 674 KiB  
Article
Occurrence of Tetrodotoxin in Bivalves and Gastropods from Harvesting Areas and Other Natural Spaces in Spain
by Lucía Blanco, Jorge Lago, Virginia González, Beatriz Paz, Maria Rambla-Alegre and Ana G. Cabado
Toxins 2019, 11(6), 331; https://doi.org/10.3390/toxins11060331 - 11 Jun 2019
Cited by 15 | Viewed by 3617
Abstract
Tetrodotoxin (TTX) is a potent neurotoxin that is receiving increasing interest in the European Union because it has been found in different fishery products (fish, bivalves and gastropods) captured in European waters. Since available information is scarce, further analytical data regarding the incidence [...] Read more.
Tetrodotoxin (TTX) is a potent neurotoxin that is receiving increasing interest in the European Union because it has been found in different fishery products (fish, bivalves and gastropods) captured in European waters. Since available information is scarce, further analytical data regarding the incidence of this toxin in European fishery products is needed in order to perform an appropriate risk assessment devoted to protecting consumers’ health. Hence, samples of bivalves and gastropods were collected at different points of the Spanish coast and analyzed by high-performance hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) to evaluate the presence of TTX. None of the analyzed samples showed TTX above an internal threshold of 10 µg/kg or even showed a peak under it. Our results on TTX occurrence obtained in bivalve molluscs and gastropods did not show, at least in the studied areas, a risk for public health. However, taking into account previous positive results obtained by other research groups, and since we did not detect TTX in our samples, a more completed study increasing sampling frequency is needed to ensure proper risk evaluation towards the food safety of these products. Full article
(This article belongs to the Special Issue Tetrodotoxins)
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17 pages, 1834 KiB  
Article
Tetrodotoxins Occurrence in Non-Traditional Vectors of the North Atlantic Waters (Portuguese Maritime Territory, and Morocco Coast)
by Marisa Silva, Inés Rodríguez, Aldo Barreiro, Manfred Kaufmann, Ana Isabel Neto, Meryem Hassouani, Brahim Sabour, Amparo Alfonso, Luis M. Botana and Vitor Vasconcelos
Toxins 2019, 11(6), 306; https://doi.org/10.3390/toxins11060306 - 29 May 2019
Cited by 26 | Viewed by 4337
Abstract
Tetrodotoxin (TTX) is a potent alkaloid typically from tropical ecosystems, but in the last decade its presence has been more pronounced in the temperate waters of the Atlantic. In its last scientific opinion, the European Food Safety Authority (EFSA) stressed the need for [...] Read more.
Tetrodotoxin (TTX) is a potent alkaloid typically from tropical ecosystems, but in the last decade its presence has been more pronounced in the temperate waters of the Atlantic. In its last scientific opinion, the European Food Safety Authority (EFSA) stressed the need for data regarding TTX prevalence in European waters. To address EFSA’s concerns, benthic organisms such as mollusks, crustaceans, echinoderms and fish with different feeding habits were collected along the Portuguese continental coast, islands (São Miguel, Azores, and Madeira) and the northwestern Moroccan coast. A total of 165 samples were analyzed by ultra high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS) and ultra high performance chromatography mass spectrometry (UHPLC-MS/MS). Geographical tendencies were detected as follows, by descending order: S. Miguel Island (Azores), Moroccan coast, Madeira Island and Portuguese continental coast. The toxin amounts detected were significant, above the Dutch limit value established in 2017, showing the importance and the need for continuity of these studies to gain more knowledge about the prevalence of these toxins, unraveling new vectors, in order to better assess human health risk. This work represents a general overview of new TTX bearers (7) most of them in gastropods (Patella depressa, Nucella lapillus, Onchidella celtica and Aplysia depilans), followed by echinoderms (Echinus esculentus and Ophidiaster ophidianus) and puffer fish Sphoeroides marmoratus. Full article
(This article belongs to the Special Issue Tetrodotoxins)
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12 pages, 5429 KiB  
Article
Acute Toxicity Assessment: Macroscopic and Ultrastructural Effects in Mice Treated with Oral Tetrodotoxin
by Paula Abal, M. Carmen Louzao, Natalia Vilariño, Mercedes R. Vieytes and Luis M. Botana
Toxins 2019, 11(6), 305; https://doi.org/10.3390/toxins11060305 - 29 May 2019
Cited by 12 | Viewed by 4827
Abstract
Tetrodotoxin (TTX) is an extremely toxic marine compound produced by different genera of bacteria that can reach humans through ingestion mainly of pufferfish but also of other contaminated fish species, marine gastropods or bivalves. TTX blocks voltage-gated sodium channels inhibiting neurotransmission, which in [...] Read more.
Tetrodotoxin (TTX) is an extremely toxic marine compound produced by different genera of bacteria that can reach humans through ingestion mainly of pufferfish but also of other contaminated fish species, marine gastropods or bivalves. TTX blocks voltage-gated sodium channels inhibiting neurotransmission, which in severe cases triggers cardiorespiratory failure. Although TTX has been responsible for many human intoxications limited toxicological data are available. The recent expansion of TTX from Asian to European waters and diversification of TTX-bearing organisms entail an emerging risk of food poisoning. This study is focused on the acute toxicity assessment of TTX administered to mice by oral gavage following macroscopic and microscopic studies. Necropsy revealed that TTX induced stomach swelling 2 h after administration, even though no ultrastructural alterations were further detected. However, transmission electron microscopy images showed an increase of lipid droplets in hepatocytes, swollen mitochondria in spleens, and alterations of rough endoplasmic reticulum in intestines as hallmarks of the cellular damage. These findings suggested that gastrointestinal effects should be considered when evaluating human TTX poisoning. Full article
(This article belongs to the Special Issue Tetrodotoxins)
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12 pages, 1874 KiB  
Article
Response Surface Methodology for the Optimization of Ultrasound-Assisted Extraction of Tetrodotoxin from the Liver of Takifugu pseudommus
by Xiaojun Zhang, Chengcheng Han, Si Chen, Le Li, Jingjing Zong, Junjie Zeng and Guangming Mei
Toxins 2018, 10(12), 529; https://doi.org/10.3390/toxins10120529 - 10 Dec 2018
Cited by 8 | Viewed by 4472
Abstract
Tetrodotoxin (TTX) is a marine biotoxin that has high scientific value. However, the lack of efficient TTX extraction and preparation methods has led to a scarcity of TTX samples for clinical application. In this study, TTX from the liver of Takifugu pseudommus was [...] Read more.
Tetrodotoxin (TTX) is a marine biotoxin that has high scientific value. However, the lack of efficient TTX extraction and preparation methods has led to a scarcity of TTX samples for clinical application. In this study, TTX from the liver of Takifugu pseudommus was ultrasound-assisted extracted with acidified organic solvents. The extraction process was analyzed and optimized by single factor method and response surface methodology (RSM). The optimal extraction conditions predicted by a response surface model were as follows: liquid:material ratio, 2.8:1; extraction temperature, 60 °C; extraction time, 23.3 min. Under these conditions, the extraction of TTX had a yield of 89.65%, and the results were further verified by experimental extraction, and analyzed by ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). It was found that the extracts of T. pseudommus liver contained TTX and its four analogues at certain proportions (TTX: 10.4%; 5,6,11-trideoxyTTX: 83.3%; 5,11-dideoxyTTX:2.4%; 4,9-anhydro TTX:2.6%; 5-deoxyTTX:1.3%). This study demonstrates a stable and efficient extraction process of TTX from pufferfish liver, which can be helpful for further research and analysis, as well as the utilization of TTX from pufferfish. Full article
(This article belongs to the Special Issue Tetrodotoxins)
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11 pages, 1660 KiB  
Article
Detection of the Potential Inactivation of Tetrodotoxin by Lactic Acid Bacterial Exopolysaccharide
by Nguyen Hoang Khue Tu, Nghe Van Dat, Le Van Canh and Doan Thi Thanh Vinh
Toxins 2018, 10(7), 288; https://doi.org/10.3390/toxins10070288 - 12 Jul 2018
Cited by 10 | Viewed by 5032
Abstract
Screening for compounds that can neutralize the toxicity of tetrodotoxin (TTX) or reduce its negative effects is necessary. Our study tested the TTX detoxification capacity of exopolysaccharide (EPS) extracted from lactic acid bacteria. EPS of Leuconostoc mesenteroides N3 isolated from the Vung Tau [...] Read more.
Screening for compounds that can neutralize the toxicity of tetrodotoxin (TTX) or reduce its negative effects is necessary. Our study tested the TTX detoxification capacity of exopolysaccharide (EPS) extracted from lactic acid bacteria. EPS of Leuconostoc mesenteroides N3 isolated from the Vung Tau sea (Vietnam), Lactobacillus plantarum PN05, and Lactobacillus rhamnosus PN04 were used in the study. To more completely evaluate the importance of EPS in detoxification, EPS samples of Leuconostoc mesenteroides N3, Lactobacillus plantarum PN05 and Lactobacillus rhamnosus PN04 were also tested. The majority of EPS of these bacteria contained glucose; this was observed using thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) analysis. As observed with FTIR analysis, only EPS of Lactobacillus plantarum PN05 contained methyl groups. The results indicated that detoxification of TTX in mice could be obtained at an optimal dose of 248 µg EPS from Leuconostoc mesenteroides incubated with 54 µg cuprous oxide for 40 min or 148 µg EPS Lactobacillus rhamnosus incubated with 55 µg cuprous oxide for 40 min, while EPS from Lactobacillus plantarum showed TTX detoxification capacity without cuprous oxide combination. Consequently, EPS from Lactobacillus plantarum PN05 can be used in TTX prevention. This is the first report on the importance of lactic acid bacteria in TTX detoxification. Full article
(This article belongs to the Special Issue Tetrodotoxins)
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14 pages, 7560 KiB  
Article
Distribution of Tetrodotoxin in the New Zealand Clam, Paphies australis, Established Using Immunohistochemistry and Liquid Chromatography-Tandem Quadrupole Mass Spectrometry
by Laura Biessy, Kirsty F. Smith, Michael J. Boundy, Stephen C. Webb, Ian Hawes and Susanna A. Wood
Toxins 2018, 10(7), 282; https://doi.org/10.3390/toxins10070282 - 6 Jul 2018
Cited by 14 | Viewed by 5290
Abstract
Tetrodotoxin (TTX) is one of the most potent neurotoxins known. It was originally thought to only occur in puffer fish but has now been identified in twelve different classes of freshwater and marine organisms, including bivalves. Despite being one of the world’s most [...] Read more.
Tetrodotoxin (TTX) is one of the most potent neurotoxins known. It was originally thought to only occur in puffer fish but has now been identified in twelve different classes of freshwater and marine organisms, including bivalves. Despite being one of the world’s most studied biotoxins, its origin remains uncertain. There is contradictory evidence regarding the source of TTX and its pathway through food webs. To date, the distribution of TTX has not been examined in bivalves. In the present study, 48 Paphies australis, a TTX-containing clam species endemic to New Zealand, were collected. Thirty clams were dissected, and organs and tissues pooled into five categories (siphons, digestive gland, adductor muscles, and the ‘rest’) and analyzed for TTX using liquid chromatography-mass spectrometry (LC-MS). The micro-distribution of TTX was visualized in the remaining 18 individuals using an immunohistological technique incorporating a TTX-specific monoclonal antibody. The LC-MS analysis revealed that siphons contained the highest concentrations of TTX (mean 403.8 µg/kg). Immunohistochemistry analysis showed TTX in the outer cells of the siphons, but also in the digestive system, foot, and gill tissue. Observing TTX in organs involved in feeding provides initial evidence to support the hypothesis of an exogenous source in P. australis. Full article
(This article belongs to the Special Issue Tetrodotoxins)
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Review

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25 pages, 388 KiB  
Review
Public Health Risks Associated with Tetrodotoxin and Its Analogues in European Waters: Recent Advances after The EFSA Scientific Opinion
by Panagiota Katikou
Toxins 2019, 11(5), 240; https://doi.org/10.3390/toxins11050240 - 26 Apr 2019
Cited by 37 | Viewed by 5762
Abstract
Tetrodotoxin (TTX) and its analogues are naturally occurring toxins responsible worldwide for human intoxication cases and fatalities, mainly associated with pufferfish consumption. In the last decade, TTXs were detected in marine bivalves and gastropods from European waters. As TTXs are not regulated or [...] Read more.
Tetrodotoxin (TTX) and its analogues are naturally occurring toxins responsible worldwide for human intoxication cases and fatalities, mainly associated with pufferfish consumption. In the last decade, TTXs were detected in marine bivalves and gastropods from European waters. As TTXs are not regulated or monitored at EU level, their unexpected occurrence in shellfish raised concerns as a food safety hazard and revealed the necessity of a thorough assessment on the public health risks associated with their presence. For this reason, the European Food Safety Authority (EFSA) was requested by the European Commission to provide a scientific opinion, finally adopted in March 2017, according to which a provisional concentration below 44 μg TTX equivalents/kg shellfish meat, based on a large portion size of 400 g, was considered not to result in adverse effects in humans. The EFSA expert panel, however, recognized a number of shortcomings and uncertainties related to the unavailability of sufficient scientific data and provided relevant recommendations for future research to overcome these data gaps identified in order to further refine the risk assessment on TTXs. The present review aims to summarize the knowledge obtained towards addressing these recommendations in the two years following publication of the EFSA opinion, at the same time highlighting the points requiring further investigation. Full article
(This article belongs to the Special Issue Tetrodotoxins)
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