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Toxins
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Analysis and Evaluation of Tetrodotoxin
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Analysis and Evaluation of Tetrodotoxin

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

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 15024

Special Issue Editors

Dr. Paz Otero

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Guest Editor
Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, 32004 Ourense, Spain
Interests: nutrition; food technology; advanced analytical techniques; hyphenated techniques; gas chromatography; liquid chromatography; mass spectrometry; green extraction processes; compressed fluids; marine compounds; food and pharmaceutical applications; biotechnology; emergent toxins and contaminants; global food security
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Carmen Vale

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Guest Editor
Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Veterinary, University of Santiago of Compostela, 27002 Lugo, Spain
Interests: marine toxins; ion channels; neurotoxicity; pharmaceutical analysis; pharmacology, toxicology and pharmaceutics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Tetrodotoxin (TTX) is a naturally occurring toxin that may contaminate the food chain, inducing neurological symptoms in humans by selective and extracellular binding to receptor-site 1 of voltage-gated sodium channels (Nav). TTX is an extremely potent alkaloid typical of warm ecosystems that, over recent years, has appeared more frequently in countries with temperate waters, including New Zealand, Japan, UK, Netherlands, Greece, Spain, and Italy. TTX and its analogues are not monitored on a regular basis in the EU, and no maximum permitted level has been defined, although concentrations lower than 44 μg of TTX eq/kg of shellfish meat are not expected to harm humans. This Special Issue is focused on the occurrence of TTXs in new areas and in new species, the emerging risks, analytical methods for their detection and quantification, rapid tests for screening, and the in vivo and in vitro toxicology, mode of action, and effects on neuronal function and brain development. Moreover, the chronic effects of low doses of neurotoxins on animal and human health are also of interest.

Prof. Paz Otero
Prof. Carmen Vale
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tetrodotoxin (TTX)
  • detection methods
  • emerging risks
  • developmental neurotoxicity
  • voltage-gated channels
  • neurotransmitter receptors

Published Papers (5 papers)

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Research

13 pages, 1851 KiB  
Article
Tetrodotoxins Secretion and Voltage-Gated Sodium Channel Adaptation in the Ribbon Worm Kulikovia alborostrata (Takakura, 1898) (Nemertea)
by Anna E. Vlasenko, Vasiliy G. Kuznetsov, Grigorii V. Malykin, Alexandra O. Pereverzeva, Peter V. Velansky, Konstantin V. Yakovlev and Timur Yu. Magarlamov
Toxins 2021, 13(9), 606; https://doi.org/10.3390/toxins13090606 - 29 Aug 2021
Cited by 8 | Viewed by 2068
Abstract
Nemertea is a phylum of marine worms whose members bear various toxins, including tetrodotoxin (TTX) and its analogues. Despite the more than 30 years of studying TTXs in nemerteans, many questions regarding their functions and the mechanisms ensuring their accumulation and usage remain [...] Read more.
Nemertea is a phylum of marine worms whose members bear various toxins, including tetrodotoxin (TTX) and its analogues. Despite the more than 30 years of studying TTXs in nemerteans, many questions regarding their functions and the mechanisms ensuring their accumulation and usage remain unclear. In the nemertean Kulikovia alborostrata, we studied TTX and 5,6,11-trideoxyTTX concentrations in body extracts and in released mucus, as well as various aspects of the TTX-positive-cell excretion system and voltage-gated sodium (Nav1) channel subtype 1 mutations contributing to the toxins’ accumulation. For TTX detection, an immunohistological study with an anti-TTX antibody and HPLC-MS/MS were conducted. For Nav1 mutation searching, PCR amplification with specific primers, followed by Sanger sequencing, was used. The investigation revealed that, in response to an external stimulus, subepidermal TTX-positive cells released secretions actively to the body surface. The post-release toxin recovery in these cells was low for TTX and high for 5,6,11-trideoxyTTX in captivity. According to the data obtained, there is low probability of the targeted usage of TTX as a repellent, and targeted 5,6,11-trideoxyTTX secretion by TTX-bearing nemerteans was suggested as a possibility. The Sanger sequencing revealed identical sequences of the P-loop regions of Nav1 domains I–IV in all 17 studied individuals. Mutations comprising amino acid substitutions, probably contributing to nemertean channel resistance to TTX, were shown. Full article
(This article belongs to the Special Issue Analysis and Evaluation of Tetrodotoxin)
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9 pages, 1329 KiB  
Communication
The First Data on the Complete Genome of a Tetrodotoxin-Producing Bacterium
by Daria I. Melnikova, Reindert Nijland and Timur Yu. Magarlamov
Toxins 2021, 13(6), 410; https://doi.org/10.3390/toxins13060410 - 09 Jun 2021
Cited by 2 | Viewed by 3893
Abstract
Tetrodotoxin (TTX)-producing bacteria have attracted great interest as a model system for study of the TTX biosynthetic route. Here, we report the complete genome of the TTX-producing bacterium Bacillus sp. 1839. The genome of the strain Bacillus sp. 1839, previously isolated from the [...] Read more.
Tetrodotoxin (TTX)-producing bacteria have attracted great interest as a model system for study of the TTX biosynthetic route. Here, we report the complete genome of the TTX-producing bacterium Bacillus sp. 1839. The genome of the strain Bacillus sp. 1839, previously isolated from the TTX-bearing marine ribbon worm Cephalothrix cf. simula, was obtained using second generation Illumina and third generation nanopore sequencing technologies. Phylogenetic analysis has classified this strain as Cytobacillus gottheilii. Full article
(This article belongs to the Special Issue Analysis and Evaluation of Tetrodotoxin)
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16 pages, 2660 KiB  
Article
Comparative Transcriptome Analysis of Toxic and Non-Toxic Nassarius Communities and Identification of Genes Involved in TTX-Adaptation
by Shanmei Zou
Toxins 2020, 12(12), 761; https://doi.org/10.3390/toxins12120761 - 02 Dec 2020
Cited by 5 | Viewed by 2049
Abstract
Nassarius has caused serious people poisoning and death incident as a popular food due to tetrodotoxin (TTX) accumulation in their body. Understanding the genetic basis of tetrodotoxin (TTX) transformation and resistance in animals could lead to significant insights into adaptive evolution to toxins [...] Read more.
Nassarius has caused serious people poisoning and death incident as a popular food due to tetrodotoxin (TTX) accumulation in their body. Understanding the genetic basis of tetrodotoxin (TTX) transformation and resistance in animals could lead to significant insights into adaptive evolution to toxins and toxin poisoning cures in medicine. Here we performed comparative transcriptome analysis for toxic and non-toxic communities in Nassarius succinctus and Nassarius variciferus to reveal their genetic expression and mutation patterns. For both species, the cellular and metabolic process, and binding and catalytic activity accounted for the top classification categories, and the toxic communities generally produced more up-regulated genes than non-toxic communities. Most unigenes and different expression genes were related to disease, e.g., heat shock protein and tissue factor pathway inhibitors, which involve detoxification and coagulation. In mutation levels, the sodium channel gene of N. succinctus had one amino acid mutation “L”, which is different from that of other animals. In conclusion, the comparative transcriptome analysis of different species and populations provided an important genetic basis for adaptive evolution to toxins, health and toxin poisoning cure research for TTX in marine gastropoda mollusk. Future studies will focus on the action mechanism of the important functional gene for TTX accumulation and resistance. Full article
(This article belongs to the Special Issue Analysis and Evaluation of Tetrodotoxin)
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12 pages, 2813 KiB  
Article
Survey of Tetrodotoxin in New Zealand Bivalve Molluscan Shellfish over a 16-Month Period
by Michael J. Boundy, Laura Biessy, Brian Roughan, Jeane Nicolas and D. Tim Harwood
Toxins 2020, 12(8), 512; https://doi.org/10.3390/toxins12080512 - 10 Aug 2020
Cited by 12 | Viewed by 3314
Abstract
Tetrodotoxin (TTX) is a heat-stable neurotoxin typically associated with pufferfish intoxications. It has also been detected in shellfish from Japan, the United Kingdom, Greece, China, Italy, the Netherlands and New Zealand. A recent European Food Safety Authority (EFSA) scientific opinion concluded that a [...] Read more.
Tetrodotoxin (TTX) is a heat-stable neurotoxin typically associated with pufferfish intoxications. It has also been detected in shellfish from Japan, the United Kingdom, Greece, China, Italy, the Netherlands and New Zealand. A recent European Food Safety Authority (EFSA) scientific opinion concluded that a level of <0.044 mg TTX/kg in marine bivalves and gastropods, based on a 400 g portion size, does not result in adverse effects in humans. There have been no reports of human illness attributed to the consumption of New Zealand shellfish containing TTX. To obtain a greater understanding of its presence, a survey of non-commercial New Zealand shellfish was performed between December 2016 and March 2018. During this period, 766 samples were analysed from 8 different species. TTX levels were found to be low and similar to those observed in shellfish from other countries, except for pipi (Paphies australis), a clam species endemic to New Zealand. All pipi analysed as part of the survey were found to contain detectable levels of TTX, and pipi from a sampling site in Hokianga Harbour contained consistently elevated levels. In contrast, no TTX was observed in cockles from this same sampling site. No recreationally harvested shellfish species, including mussels, oysters, clams and tuatua, contained TTX levels above the recommended EFSA safe guidance level. The levels observed in shellfish were considerably lower than those reported in other marine organisms known to contain TTX and cause human intoxication (e.g., pufferfish). Despite significant effort, the source of TTX in shellfish, and indeed all animals, remains unresolved making it a difficult issue to understand and manage. Full article
(This article belongs to the Special Issue Analysis and Evaluation of Tetrodotoxin)
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18 pages, 3151 KiB  
Article
Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin
by Andrea Boente-Juncal, Paz Otero, Inés Rodríguez, Mercedes Camiña, Mercedes Rodriguez-Vieytes, Carmen Vale and Luis M. Botana
Toxins 2020, 12(5), 312; https://doi.org/10.3390/toxins12050312 - 09 May 2020
Cited by 13 | Viewed by 3103
Abstract
Tetrodotoxin (TTX) is a potent natural toxin causative of human food intoxications that shares its mechanism of action with the paralytic shellfish toxin saxitoxin (STX). Both toxins act as potent blockers of voltage-gated sodium channels. Although human intoxications by TTX were initially described [...] Read more.
Tetrodotoxin (TTX) is a potent natural toxin causative of human food intoxications that shares its mechanism of action with the paralytic shellfish toxin saxitoxin (STX). Both toxins act as potent blockers of voltage-gated sodium channels. Although human intoxications by TTX were initially described in Japan, nowadays increasing concern about the regulation of this toxin in Europe has emerged due to its detection in fish and mollusks captured in European waters. Currently, TTX is only regularly monitored in Dutch fishery products. However, the European Food Safety Authority (EFSA) has established a safety level of 44 µg/kg TTX as the amount of toxin that did not cause adverse effects in humans. This level was extrapolated considering initial data on its acute oral toxicity and EFSA remarked the need for chronic toxicity studies to further reduce the uncertainty of future toxin regulations. Thus, in this work, we evaluated the oral chronic toxicity of TTX using the safety levels initially recommended by EFSA in order to exclude potential human health risks associated with the worldwide expanding presence of TTX. Using internationally recommended guidelines for the assessment of oral chronic toxicity, the data provided here support the proposed safety level for TTX as low enough to prevent human adverse effects of TTX even after chronic daily exposure to the toxin. However, the combination of TTX with STX at doses above the maximal exposure level of 5.3 µg/kg body weight derived by EFSA increased the lethality of TTX, thus confirming that both TTX and paralytic shellfish toxins should be taken into account to assess human health risks. Full article
(This article belongs to the Special Issue Analysis and Evaluation of Tetrodotoxin)
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