-
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 -
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 -
Nature Communications Jan 2024Tetrodotoxin and congeners are specific voltage-gated sodium channel blockers that exhibit remarkable anesthetic and analgesic effects. Here, we present a scalable...
Tetrodotoxin and congeners are specific voltage-gated sodium channel blockers that exhibit remarkable anesthetic and analgesic effects. Here, we present a scalable asymmetric syntheses of Tetrodotoxin and 9-epiTetrodotoxin from the abundant chemical feedstock furfuryl alcohol. The optically pure cyclohexane skeleton is assembled via a stereoselective Diels-Alder reaction. The dense heteroatom substituents are established sequentially by a series of functional group interconversions on highly oxygenated cyclohexane frameworks, including a chemoselective cyclic anhydride opening, and a decarboxylative hydroxylation. An innovative SmI-mediated concurrent fragmentation, an oxo-bridge ring opening and ester reduction followed by an Upjohn dihydroxylation deliver the highly oxidized skeleton. Ruthenium-catalyzed oxidative alkyne cleavage and formation of the hemiaminal and orthoester under acidic conditions enable the rapid assembly of Tetrodotoxin, anhydro-Tetrodotoxin, 9-epiTetrodotoxin, and 9-epi lactone-Tetrodotoxin.
Topics: Tetrodotoxin; Hydroxylation; Oxidative Stress; Cyclohexanes; Radiopharmaceuticals
PubMed: 38263179
DOI: 10.1038/s41467-024-45037-0 -
Nano Letters Feb 2017An injectable local anesthetic producing repeatable on-demand nerve block would be desirable for pain management. Here we present a phototriggerable device to achieve...
An injectable local anesthetic producing repeatable on-demand nerve block would be desirable for pain management. Here we present a phototriggerable device to achieve repeatable and adjustable on-demand local anesthesia in superficial or deep tissues, consisting of gold nanorods attached to low temperature sensitive liposomes (LTSL). The particles were loaded with tetrodotoxin and dexmedetomidine. Near-infrared light (NIR, 808 nm, continuous wave) could heat gold nanorods at low fluence (short duration and low irradiance), leading to rapid release of payload. In vivo, 1-2 min of irradiation at ≤272 mW/cm produced repeatable and adjustable on-demand infiltration anesthesia or sciatic nerve blockade with minimal toxicity. The nerve block intensity and duration correlated with the irradiance and duration of the applied light.
Topics: Anesthesia, Local; Animals; Dexmedetomidine; Drug Liberation; Gold; Infrared Rays; Light; Liposomes; Nanotubes; Nerve Block; Particle Size; Rats; Sciatic Nerve; Surface Properties; Tetrodotoxin; Tissue Distribution
PubMed: 28058845
DOI: 10.1021/acs.nanolett.6b03588 -
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 -
Toxins Jul 2020Pufferfish of the family Tetraodontidae possess tetrodotoxin (TTX) and/or saxitoxins (STXs), but the toxin ratio differs, depending on the genus or species. In the...
Pufferfish of the family Tetraodontidae possess tetrodotoxin (TTX) and/or saxitoxins (STXs), but the toxin ratio differs, depending on the genus or species. In the present study, to clarify the distribution profile of TTX and STXs in Tetraodontidae, we investigated the composition and intra-body distribution of the toxins in . specimens (four male and six female) were collected from Amami-Oshima Island, Kagoshima Prefecture, Japan, and the toxins were extracted from the muscle, liver, intestine, gallbladder, gonads, and skin. Analysis of the extracts for TTX by liquid chromatography tandem mass spectrometry and of STXs by high-performance liquid chromatography with post-column fluorescence derivatization revealed TTX, as well as a large amount of STXs, with neoSTX as the main component and dicarbamoylSTX and STX itself as minor components, in the skin and ovary. The toxins were also detected in the other tissues, but in much lower amounts than in the skin and ovary. The TTX/STX ratio varied greatly, depending on the tissue, but TTX was the major toxin component in the whole body, and STXs accounted for 25% and 13% of the total toxin amount in males and females, respectively. Like the marine pufferfish of the genus , should be considered a pufferfish with considerable amounts of both TTX and STXs present simultaneously.
Topics: Animals; Biological Assay; Female; Male; Mice; Saxitoxin; Tetraodontiformes; Tetrodotoxin; Tissue Distribution; Toxicity Tests
PubMed: 32635254
DOI: 10.3390/toxins12070436 -
Toxins Aug 2022Tetrodotoxin (TTX), a potent paralytic sodium channel blocker, is an intriguing marine toxin. Widely distributed in nature, TTX has attracted attention in various... (Review)
Review
Tetrodotoxin (TTX), a potent paralytic sodium channel blocker, is an intriguing marine toxin. Widely distributed in nature, TTX has attracted attention in various scientific fields, from biomedical studies to environmental safety concerns. Despite a long history of studies, many issues concerning the biosynthesis, origin, and spread of TTX in animals and ecosystems remain. This review aims to summarize the current knowledge on TTX circulation inside TTX-bearing animal bodies. We focus on the advances in TTX detection at the cellular and subcellular levels, providing an expanded picture of intra-organismal TTX migration mechanisms. We believe that this review will help address the gaps in the understanding of the biological function of TTX and facilitate the development of further studies involving TTX-bearing animals.
Topics: Animals; Ecosystem; Sodium Channel Blockers; Tetrodotoxin
PubMed: 36006238
DOI: 10.3390/toxins14080576 -
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 Applied Microbiology Oct 2015Tetrodotoxin (TTX) is a deadly neurotoxin which selectively inhibits Na(+) activation mechanism of nerve impulse, without affecting the permeability of K(+) ions.... (Review)
Review
Tetrodotoxin (TTX) is a deadly neurotoxin which selectively inhibits Na(+) activation mechanism of nerve impulse, without affecting the permeability of K(+) ions. Because of this sodium channel blocking action, it is majorly being studied for biomedical applications. TTX is present in taxonomically diverse groups of animals inhabiting terrestrial, marine, fresh water and brackish water environments, still its origin remains unclear. The extensive study of the toxin has revealed a few possibilities of its origin. This review reports on the aspects of the origin of TTX, where the primary focus is on its exogenous origin. The significance of bacterial, cellular and environmental factors in its biogenesis and accumulation is also discussed. The possible facets for engineering the bacterial genomics to modulate the gene expression for TTX production are also outlined.
Topics: Animals; Bacteria; Humans; Neurotoxins; Tetrodotoxin
PubMed: 26178523
DOI: 10.1111/jam.12896 -
Toxins Jul 2021Visceral pain is one of the most common symptoms associated with functional gastrointestinal (GI) disorders. Although the origin of these symptoms has not been clearly... (Review)
Review
Visceral pain is one of the most common symptoms associated with functional gastrointestinal (GI) disorders. Although the origin of these symptoms has not been clearly defined, the implication of both the central and peripheral nervous systems in visceral hypersensitivity is well established. The role of several pathways in visceral nociception has been explored, as well as the influence of specific receptors on afferent neurons, such as voltage-gated sodium channels (VGSCs). VGSCs initiate action potentials and dysfunction of these channels has recently been associated with painful GI conditions. Current treatments for visceral pain generally involve opioid based drugs, which are associated with important side-effects and a loss of effectiveness or tolerance. Hence, efforts have been intensified to find new, more effective and longer-lasting therapies. The implication of VGSCs in visceral hypersensitivity has drawn attention to tetrodotoxin (TTX), a relatively selective sodium channel blocker, as a possible and promising molecule to treat visceral pain and related diseases. As such, here we will review the latest information regarding this toxin that is relevant to the treatment of visceral pain and the possible advantages that it may offer relative to other treatments, alone or in combination.
Topics: Action Potentials; Animals; Ganglia, Spinal; Humans; Nociception; Sodium Channel Blockers; Tetrodotoxin; Visceral Pain; Voltage-Gated Sodium Channels
PubMed: 34357968
DOI: 10.3390/toxins13070496