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Toxins Feb 2014Tetrodotoxin (TTX) is a naturally occurring toxin that has been responsible for human intoxications and fatalities. Its usual route of toxicity is via the ingestion of... (Review)
Review
Tetrodotoxin (TTX) is a naturally occurring toxin that has been responsible for human intoxications and fatalities. Its usual route of toxicity is via the ingestion of contaminated puffer fish which are a culinary delicacy, especially in Japan. TTX was believed to be confined to regions of South East Asia, but recent studies have demonstrated that the toxin has spread to regions in the Pacific and the Mediterranean. There is no known antidote to TTX which is a powerful sodium channel inhibitor. This review aims to collect pertinent information available to date on TTX and its analogues with a special emphasis on the structure, aetiology, distribution, effects and the analytical methods employed for its detection.
Topics: Animals; Food Contamination; Food Safety; Humans; Molecular Structure; Sodium Channel Blockers; Tetrodotoxin
PubMed: 24566728
DOI: 10.3390/toxins6020693 -
Channels (Austin, Tex.) 2008Tetrodotoxin (TTX) is a potent toxin that specifically binds to voltage gated sodium channels. TTX binding physically blocks the flow of sodium ions through the channel,... (Review)
Review
Tetrodotoxin (TTX) is a potent toxin that specifically binds to voltage gated sodium channels. TTX binding physically blocks the flow of sodium ions through the channel, thereby preventing action potential (AP) generation and propagation. TTX has different binding affinities for different sodium channel isoforms. These differences are imparted by amino acid substitutions. Such substitutions confer TTX resistance to a variety of species. Tetrodotoxin resistance, however, may come at a cost to performance caused by changes in the biophysical properties and/or ion selectivity of the TTX resistant sodium channels. We here review the properties of sodium channels and their interaction with TTX, and look at some special examples of TTX resistant channels wherein the benefit of toxin resistance may be offset by other behavioral costs.
Topics: Animals; Humans; Ion Channel Gating; Neurotoxins; Sodium Channel Blockers; Sodium Channels; Tetrodotoxin
PubMed: 19098433
DOI: 10.4161/chan.2.6.7429 -
Toxins May 2022Tetrodotoxin is one of the most potent neurotoxins in the aquatic world. This review of published and unpublished reports aims to describe the poisoning cases that have... (Review)
Review
Tetrodotoxin is one of the most potent neurotoxins in the aquatic world. This review of published and unpublished reports aims to describe the poisoning cases that have occurred in mainland France and overseas territories. Six articles were included, with 13 poisoning events, individuals or collective (number () = 53 patients). Moreover, 13 unpublished poisoning events from toxicovigilance networks were found ( = 17). All cases happened in overseas territories: French Guyana ( = 7), New Caledonia ( = 11), Reunion ( = 35) and French Polynesia ( = 17). The median age was 36 years. The most frequent signs were neurological (81.8%), digestive (54.5%) and general (52.3%). Three cases of dysgueusia and nine cases of urogenital discomfort were observed in French Polynesia. Twelve severe cases were reported, including seven deaths. Only three events (11.5%) were documented by a tetrodotoxin assay. Two families of fish accounted for 91.6% of the poisonings: 33.3% due to the Diodontidae family and 58.3% to the Tetraodontidae family. Although rare, information and collection campaigns on tetrodotoxin poisoning are, therefore, essential.
Topics: Animals; Ciguatera Poisoning; France; Humans; Neurotoxicity Syndromes; Tetraodontiformes; Tetrodotoxin
PubMed: 35622597
DOI: 10.3390/toxins14050351 -
Journal of Agricultural and Food... Oct 2022Tetrodotoxin (TTX), found in various organisms including pufferfish, is an extremely potent marine toxin responsible for numerous food poisoning accidents. Due to its... (Review)
Review
Tetrodotoxin (TTX), found in various organisms including pufferfish, is an extremely potent marine toxin responsible for numerous food poisoning accidents. Due to its serious toxicity and public health threat, detecting TTX and its analogues in diverse food matrices with a simple, fast, efficient method has become a worldwide concern. This review summarizes the advances in sample preparation and analytical methods for the determination of TTX and its analogues, focusing on the latest development over the past five years. Current state-of-the-art technologies, such as solid-phase microextraction, online technology, novel injection technology, two-dimensional liquid chromatography, high-resolution mass spectrometry, newly developed lateral flow immunochromatographic strips, immunosensors, dual-mode aptasensors, and nanomaterials-based approaches, are thoroughly discussed. The advantages and limitations of different techniques, critical comments, and future perspectives are also proposed. This review is expected to provide rewarding insights to the future development and broad application of pretreatment and detection methods for TTX and its analogues.
Topics: Animals; Biosensing Techniques; Immunoassay; Tandem Mass Spectrometry; Tetraodontiformes; Tetrodotoxin
PubMed: 36153990
DOI: 10.1021/acs.jafc.2c04106 -
Toxins May 2017This review is devoted to the marine bacterial producers of tetrodotoxin (TTX), a potent non-protein neuroparalytic toxin. In addition to the issues of the ecology and... (Review)
Review
This review is devoted to the marine bacterial producers of tetrodotoxin (TTX), a potent non-protein neuroparalytic toxin. In addition to the issues of the ecology and distribution of TTX-producing bacteria, this review examines issues relating to toxin migration from bacteria to TTX-bearing animals. It is shown that the mechanism of TTX extraction from toxin-producing bacteria to the environment occur through cell death, passive/active toxin excretion, or spore germination of spore-forming bacteria. Data on TTX microdistribution in toxic organs of TTX-bearing animals indicate toxin migration from the digestive system to target organs through the transport system of the organism. The role of symbiotic microflora in animal toxicity is also discussed: despite low toxin production by bacterial strains in laboratory conditions, even minimal amounts of TTX produced by intestinal microflora of an animal can contribute to its toxicity. Special attention is paid to methods of TTX detection applicable to bacteria. Due to the complexity of toxin detection in TTX-producing bacteria, it is necessary to use several methods based on different methodological approaches. Issues crucial for further progress in detecting natural sources of TTX investigation are also considered.
Topics: Animals; Bacteria; Bacterial Physiological Phenomena; Biodiversity; Drug Industry; Tetrodotoxin
PubMed: 28513564
DOI: 10.3390/toxins9050166 -
Current Biology : CB Oct 2016In this Quick Guide, Lorentz et al. discuss the function of tetrodotoxin and its distribution in the animal kingdom.
In this Quick Guide, Lorentz et al. discuss the function of tetrodotoxin and its distribution in the animal kingdom.
Topics: Animals; Invertebrates; Neurotoxins; Organ Specificity; Tetrodotoxin; Vertebrates
PubMed: 27728785
DOI: 10.1016/j.cub.2016.05.067 -
Tetrahedron Aug 1965
Topics: Animals; Chemical Phenomena; Chemistry; Female; Fishes, Poisonous; Ovary; Tetrodotoxin
PubMed: 5896483
DOI: 10.1016/s0040-4020(01)98344-9 -
Toxins Jul 2021Tetrodotoxin (TTX) is a potent neurotoxin that was first identified in pufferfish but has since been isolated from an array of taxa that host TTX-producing bacteria.... (Review)
Review
Tetrodotoxin (TTX) is a potent neurotoxin that was first identified in pufferfish but has since been isolated from an array of taxa that host TTX-producing bacteria. However, determining its origin, ecosystem roles, and biomedical applications has challenged researchers for decades. Recognized as a poison and for its lethal effects on humans when ingested, TTX is primarily a powerful sodium channel inhibitor that targets voltage-gated sodium channels, including six of the nine mammalian isoforms. Although lethal doses for humans range from 1.5-2.0 mg TTX (blood level 9 ng/mL), when it is administered at levels far below LD, TTX exhibits therapeutic properties, especially to treat cancer-related pain, neuropathic pain, and visceral pain. Furthermore, TTX can potentially treat a variety of medical ailments, including heroin and cocaine withdrawal symptoms, spinal cord injuries, brain trauma, and some kinds of tumors. Here, we (i) describe the perplexing evolution and ecology of tetrodotoxin, (ii) review its mechanisms and modes of action, and (iii) offer an overview of the numerous ways it may be applied as a therapeutic. There is much to be explored in these three areas, and we offer ideas for future research that combine evolutionary biology with therapeutics. The TTX system holds great promise as a therapeutic and understanding the origin and chemical ecology of TTX as a poison will only improve its general benefit to humanity.
Topics: Animals; Drug Resistance; Ecology; Humans; Neurotoxins; Phylogeny; Poisons; Sodium Channel Blockers; Tetrodotoxin
PubMed: 34437388
DOI: 10.3390/toxins13080517 -
Angewandte Chemie (International Ed. in... Apr 2020A total synthesis of tetrodotoxin was accomplished. A Diels-Alder reaction between a known enone and a siloxy diene gave a tricyclic product, the steric bias of which...
A total synthesis of tetrodotoxin was accomplished. A Diels-Alder reaction between a known enone and a siloxy diene gave a tricyclic product, the steric bias of which was used to construct the remaining stereogenic centers. A nitrogen atom was introduced either by a four-step sequence involving a Curtius rearrangement, or a three-step sequence featuring a newly developed transformation of a terminal alkyne into a nitrile. Introduction of the guanidine moiety followed by the formation of the heterocyclic system by cascade reactions led to tetrodotoxin.
Topics: Alkynes; Chemistry Techniques, Synthetic; Guanidine; Nitriles; Nitrogen; Tetrodotoxin
PubMed: 31985136
DOI: 10.1002/anie.201916611 -
Trends in Biochemical Sciences Mar 1988
Topics: Animals; Models, Molecular; Tetrodotoxin
PubMed: 3245066
DOI: 10.1016/0968-0004(88)90041-2