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Oxid Med Cell Longev 2022 24;2022:6125711. Epub 2022 May 24.

Experimental and Clinical Research Center (ECRC), A Cooperation between Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany.

In neuroinflammatory and neurodegenerative disorders such as multiple sclerosis, mitochondrial damage caused by oxidative stress is believed to contribute to neuroaxonal damage. Previously, we demonstrated that exposure to hydrogen peroxide (HO) alters mitochondrial morphology and motility in myelinated axons and that these changes initiate at the nodes of Ranvier, where numerous sodium channels are located. Therefore, we suggested that mitochondrial damage may lead to ATP deficit, thereby affecting the efficiency of the sodium-potassium ATPase and eventually leading to sodium overload in axons. Read More

Toxins (Basel) 2022 05 17;14(5). Epub 2022 May 17.

Department of Research an Biostatistics, University Hospital of Guadeloupe, LAMIA (EA4540) French West Indies University, 97159 Pointe-à-Pitre, France.

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 This review of published and unpublished reports aims to describe the poisoning cases that have occurred in mainland France and overseas territories.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). Read More

J Hazard Mater 2022 07 14;434:128925. Epub 2022 Apr 14.

Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, Qingdao 266237, China. Electronic address:

Characterizing marine biotoxins (MBs) composition in coastal aerosol particles has become essential to tracking sources of atmospheric contaminants and assessing human inhalable exposure risks to air particles. Here, coastal aerosol particles were collected over an almost 3-year period for the analysis of eight representative MBs, including brevetoxin (BTX), okadaic acid (OA), pectenotoxin-2 (PTX-2), domoic acid (DA), tetrodotoxin (TTX), saxitoxin (STX), ciguatoxin (CTX) and ω-Conotoxin. Our data showed that the levels of inhalable airborne marine biotoxins (AMBs) varied greatly among the subcategories and over time. Read More

Toxicon 2022 Jul 11;213:7-12. Epub 2022 Apr 11.

Department of Biology, Utah State University, 5305 Old Main Hill, Logan UT 84322, USA.

The origin and biogenesis of tetrodotoxin (TTX) is one of the most interesting and perplexing questions remaining for TTX researchers. Newts can possess extreme quantities of TTX and are one of the most well-studied of all TTX-bearing organisms, yet seemingly conflicting results between studies on closely related species continues to generate debate. In this study, eggs from 12 female newts (Taricha granulosa) were reared in captivity and the metamorphosed juveniles were fed a TTX-free diet for 3 years. Read More

Prog Chem Org Nat Prod 2022 ;118:101-130

Graduate School of Agricultural Science & Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 468-1 Aramaki-Aza-Aoba, Aoba-ku, Sendai, Miyagi, 980-8572, Japan.

The North American newt genera Taricha and Notophthalmus (order Caudata) are well known for the combination of potent toxicity, aposematic coloration, and striking defense postures that protects these animals from predation. This suite of traits is centered around the neurotoxin tetrodotoxin, which causes paralysis and death in metazoans by disrupting the initiation and propagation of electrical signals in the nerves and muscles. Tetrodotoxin defends newts from predation across multiple life history stages and its role in generating arms-race coevolution between Taricha newts and garter snake (genus Thamnophis) predators is well studied. Read More

Int J Mol Sci 2022 Mar 12;23(6). Epub 2022 Mar 12.

Fisheries Research Institute of Fujian, Key Laboratory of Cultivation and High-Value Utilization of Marine Organisms in Fujian Province, Xiamen 361013, China.

Pufferfish are considered a culinary delicacy but require careful preparation to avoid ingestion of the highly toxic tetrodotoxin (TTX), which accumulates in certain tissues. In this study, the tissue distribution of peroxiredoxin-1 from was investigated. The peroxiredoxin-1 protein was obtained by in vitro recombinant expression and purification. Read More

Toxicol Sci 2022 04;187(1):127-138

Division of Toxicology, Wageningen University, 6708 WE Wageningen, The Netherlands.

In this study, the ability of a new in vitro/in silico quantitative in vitro-in vivo extrapolation (QIVIVE) methodology was assessed to predict the in vivo neurotoxicity of tetrodotoxin (TTX) in rodents. In vitro concentration-response data of TTX obtained in a multielectrode array assay with primary rat neonatal cortical cells and in an effect study with mouse neuro-2a cells were quantitatively extrapolated into in vivo dose-response data, using newly developed physiologically based kinetic (PBK) models for TTX in rats and mice. Incorporating a kidney compartment accounting for active renal excretion in the PBK models proved to be essential for its performance. Read More

Toxins (Basel) 2022 02 18;14(2). Epub 2022 Feb 18.

Department of Marine Science and Resources, Nihon University, Fujisawa 252-0880, Japan.

Tetrodotoxin (TTX)-bearing fish ingest TTX from their preys through the food chain and accumulate TTX in their bodies. Although a wide variety of TTX-bearing organisms have been reported, the missing link in the TTX supply chain has not been elucidated completely. Here, we investigated the composition of TTX and 5,6,11-trideoxyTTX in juveniles of the pufferfish, , and toxic goby, , using LC-MS/MS, to resolve the missing link in the TTX supply chain. Read More

Toxins (Basel) 2022 02 8;14(2). Epub 2022 Feb 8.

Laboratory of Plankton and Shellfish Toxicity, Institute of Oceanography and Fisheries, Šetalište Ivana Meštrovića 63, 21000 Split, Croatia.

Pufferfishes are among the best-known marine organisms that accumulate marine biotoxins such as Tetrodotoxin (TTX). In the Mediterranean Sea, the silver-cheeked toadfish is the most reported TTX-bearer, causing many fatal and non-fatal cases. In Lebanon, no previous studies have measured TTX levels although the possibility of TTX-poisoning is high since is caught in different sizes and can be mistaken with other small fishes. Read More

Annu Rev Anim Biosci 2022 02;10:63-80

Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California, USA; email:

Toxin evolution in animals is one of the most fascinating and complex subjects of scientific inquiry today. Gaining an understanding of toxins poses a multifaceted challenge given the diverse modes of acquisition, evolutionary adaptations, and abiotic components that affect toxin phenotypes. Here, we highlight some of the main genetic and ecological factors that influence toxin evolution and discuss the role of antagonistic interactions and coevolutionary dynamics in shaping the direction and extent of toxicity and resistance in animals. Read More

Toxicon X 2022 Mar 22;13:100092. Epub 2022 Jan 22.

Museum of Vertebrate Zoology and Department of Integrative Biology, University of California Berkeley, Berkeley, CA, 94720, USA.

Toads of the genus are chemically defended by a unique combination of endogenously synthesized cardiotoxins (bufadienolides) and neurotoxins which may be sequestered (guanidinium alkaloids). Investigation into small-molecule chemical defenses has been primarily concerned with identifying and characterizing various forms of these toxins while largely overlooking their ecological roles and evolutionary implications. In addition to describing the extent of knowledge about toxin structures, pharmacology, and biological sources, we review the detection, identification, and quantification methods used in studies of toxins to date and conclude that many known toxin profiles are unlikely to be comprehensive because of methodological and sampling limitations. Read More

Transl Vis Sci Technol 2022 01;11(1):33

Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Institutes of Medicine, Boston, MA, USA.

Purpose: Prolonged local anesthesia (PLA) of the cornea is currently assumed to cause neurotrophic keratitis and is strongly discouraged. We investigate whether PLA of the cornea per se causes neurotrophic keratitis.

Methods: PLA of the cornea was induced in 12 female albino BALB/c mice by retrobulbar injection of a polymeric prodrug (PGS-TTX) where the site 1 sodium channel blocker tetrodotoxin (TTX) was slowly released from the polymer polyglycerol sebacate. Read More

Compr Rev Food Sci Food Saf 2022 01 26;21(1):719-737. Epub 2021 Dec 26.

Microbial Ecology and Microrganisms Genomics Laboratory, Istituto Zooprofilattico Sperimentale delle Venezie, Viale dell'Università, Legnaro, Italy.

Tetrodotoxins (TTXs) are a group of potent neurotoxins named after the Tetraodontidae fish family (pufferfish). TTXs have been reported in several animal taxa, both terrestrial and marine. The ingestion of TTX-contaminated flesh can cause serious neurotoxic symptomatology and can eventually lead to death. Read More

Toxins (Basel) 2021 12 13;13(12). Epub 2021 Dec 13.

Institute of Marine Biological Resources and Inland Waters, Hellenic Centre for Marine Research (HCMR), 71500 Heraklion, Greece.

The invasion of the tetrodotoxin (TTX)-bearing silver-cheeked toadfish and potential poisoning due to its consumption (tetrodotoxication) threatens public safety in the Mediterranean Sea. In this study, TTX and TTX analogues of (Gmelin, 1789) were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) in fish collected off the island of Crete (Southern Mediterranean). We tested the synergistic effect of a suite of factors potentially affecting toxins' levels and tetrodotoxication risk using general and generalized linear models, respectively. Read More

Mar Drugs 2021 Nov 26;19(12). Epub 2021 Nov 26.

Graduate School of Fisheries and Environmental Sciences, Nagasaki University, Bunkyo-machi 1-14, Nagasaki 852-8521, Japan.

Toxic crabs of the family Xanthidae contain saxitoxins (STXs) and/or tetrodotoxin (TTX), but the toxin ratio differs depending on their habitat. In the present study, to clarify within reef variations in the toxin profile of xanthid crabs, we collected specimens of the toxic xanthid crab and their sampling location within a single reef (Yoshihara reef) on Ishigaki Island, Okinawa Prefecture, Japan, in 2018 and 2019. The STXs/TTX content within the appendages and viscera or stomach contents of each specimen was determined by instrumental analyses. Read More

Toxicon 2021 Nov 12;203:139-146. Epub 2021 Oct 12.

Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, CEP 13560-970, São Carlos, SP, Brazil. Electronic address:

The genus Brachycephalus includes small species of aposematic anurans known as microendemic, occurring in the mountains of the Atlantic Forest. Brachycephalus ephippium, B. nodoterga and B. Read More

Toxins (Basel) 2021 08 29;13(9). Epub 2021 Aug 29.

A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, Russia.

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 , 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. Read More

Nat Biomed Eng 2021 09 13;5(9):1099-1109. Epub 2021 Sep 13.

Laboratory for Biomaterials and Drug Delivery, Department of Anaesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.

Site-1 sodium channel blockers (S1SCBs) act as potent local anaesthetics, but they can cause severe systemic toxicity. Delivery systems can be used to reduce the toxicity, but the hydrophilicity of S1SCBs makes their encapsulation challenging. Here, we report a self-assembling delivery system for S1SCBs whose design is inspired by the specific interactions of S1SCBs with two peptide sequences on the sodium channel. Read More

Toxins (Basel) 2021 07 24;13(8). Epub 2021 Jul 24.

Department of Ecology and Evolutionary Biology & UCLA La Kretz Center for California Conservation Science, Institute of the Environment and Sustainability, University of California, Los Angeles, CA 90095, USA.

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. Read More

Aquat Toxicol 2021 Aug 6;237:105908. Epub 2021 Jul 6.

Department of Marine Science and Resources, Nihon University, Fujisawa, Kanagawa 252-0880, Japan. Electronic address:

Tetrodotoxin (TTX), also known as pufferfish toxin, has been detected in marine edible bivalves worldwide. In this study, several bivalve species, Azumapecten farreri subsp. akazara, Patinopecten yessoensis and Mytilus galloprovincialis, collected from the Pacific side of the northern Japanese Islands, were studied for the accumulation of TTX in the presence of toxic planocerid larvae. Read More

Mar Drugs 2021 Jun 30;19(7). Epub 2021 Jun 30.

Service d'Ingénierie Moléculaire Pour la Santé (SIMoS), Département Médicaments et Technologies Pour la Santé (DMTS), Institut des Sciences du Vivant Frédéric Joliot, Université Paris-Saclay, CEA, ERL CNRS/CEA 9004, 91191 Gif-sur-Yvette, France.

Pacific oysters () may bio-accumulate high levels of paralytic shellfish toxins (PST) during harmful algal blooms of the genus . These blooms regularly occur in coastal waters, affecting oyster health and marketability. The aim of our study was to analyse the PST-sensitivity of nerves of Pacific oysters in relation with toxin bio-accumulation. Read More

Mol Biol Evol 2021 09;38(10):4077-4094

Department of Biological Sciences, Virginia Tech, Blacksburg, VI, USA.

Reconstructing the histories of complex adaptations and identifying the evolutionary mechanisms underlying their origins are two of the primary goals of evolutionary biology. Taricha newts, which contain high concentrations of the deadly toxin tetrodotoxin (TTX) as an antipredator defense, have evolved resistance to self-intoxication, which is a complex adaptation requiring changes in six paralogs of the voltage-gated sodium channel (Nav) gene family, the physiological target of TTX. Here, we reconstruct the origins of TTX self-resistance by sequencing the entire Nav gene family in newts and related salamanders. Read More

Harmful Algae 2021 04 13;104:101924. Epub 2020 Nov 13.

Laboratory of Aquatic Environmental Science (LAQUES), Faculty of Agriculture and Marine Science, Kochi University, 200 Otsu, Monobe, Nankoku, Kochi, 783-8502, Japan. Electronic address:

Macroalgal samples were collected from coastal waters in subboreal to subtropical zones in Japan (< 3-30 m depths) and 32 clonal strains of non-motile dinoflagellate-like protists were established. Molecular phylogenetic analyses of the LSU rDNA D1/D2, SSU rDNA, ITS region, and concatenated SSU rDNA + LSU rDNA D1/D2 sequences revealed that the strains nested within the genus Alexandrium. They were separated into three novel phylotypes: Alexandrium spp. Read More

Wei Sheng Yan Jiu 2021 Mar;50(2):296-300

Key Laboratory of Health Risk Appraisal for Trace Toxic Chemicals of Zhejiang Province, Ningbo Municipal Center for Disease Control and Prevention, Ningbo 315010, China.

Objective: Ultra-fast liquid chromatography-tandem mass spectrometry method was developed for the analysis of contamination degree of biotoxins in seafood in Ningbo City from 2017 to 2019 and the assessment of dietary exposure was conducted.

Methods: Samples were extracted and purified with optimized pretreatment process and then injected for analysis. According to the result of the measurements, an international point estimate model was used to evaluate the dietary exposure of the population. Read More

Toxicon 2021 Jul 29;198:32-35. Epub 2021 Apr 29.

Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki-Aza-Aoba, Aoba-ku, Sendai, 980-8572, Japan.

Tetrodotoxin (TTX) contents of wild-caught Chinese red-bellied newts, Cynops orientalis, and their offspring captive-reared from eggs to metamorphosed juveniles, were analysed using post-column LC-fluorescent detection (LC-FLD) and high resolution hydrophilic interaction liquid chromatography/mass spectrometry (HR-HILIC-LC/MS). TTX was detected in the parent newts and their eggs, but not in the larvae and juveniles raised under artificial condition over 20 months. However, juveniles reared in the presence of their parents, contained TTX-concentrations up to 8. Read More

Clin Toxicol (Phila) 2022 Feb 29;60(2):262-266. Epub 2021 Apr 29.

Emory University School of Medicine, Atlanta, GA, USA.

Introduction: Tetrodotoxin (TTX) is a potent sodium channel blocker, with significant neurotoxicity, found in marine animals like pufferfish and blue-ringed octopus. The severity of toxicity depends on the amount of toxin ingested and the outcome depends on the time-lapse to appropriate medical care.

Cases Report: We report five patients who presented with tetrodotoxin poisoning after consuming fried internal organs of local pufferfish from the coast of Oman. Read More

JCI Insight 2021 05 10;6(9). Epub 2021 May 10.

Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine.

Extensive activation of glial cells during a latent period has been well documented in various animal models of epilepsy. However, it remains unclear whether activated glial cells contribute to epileptogenesis, i.e. Read More

Toxins (Basel) 2021 03 31;13(4). Epub 2021 Mar 31.

Biomedical Research Center (CINBIO), Department of Analytical and Food Chemistry, Campus Universitario de Vigo, University of Vigo, 36310 Vigo, Spain.

Tetrodotoxin (TTX) is a potent neurotoxin, considered an emerging toxin in Europe where recently a safety limit of 44 µg TTX kg was recommended by authorities. In this study, three specimens of the large gastropod trumpet shell bought in a market in south Portugal were analyzed using a neuroblastoma cell (N2a) based assay and by LC-MS/MS. N2a toxicity was observed in the viscera of two individuals analyzed and LC-MS/MS showed very high concentrations of TTX (42. Read More

Mar Drugs 2021 Mar 25;19(4). Epub 2021 Mar 25.

Fisheries College, Jimei University, Xiamen 361021, China.

The von Willebrand factor type D (VWD) domain in vitellogenin has recently been found to bind tetrodotoxin. The way in which this protein domain associates with tetrodotoxin and participates in transporting tetrodotoxin in vivo remains unclear. A cDNA fragment of the vitellogenin gene containing the VWD domain from pufferfish ( (TfVWD) was cloned. Read More

Shokuhin Eiseigaku Zasshi 2021 ;62(1):28-32

Department of Agro-Food Science, Niigata Agro-Food University.

Marine pufferfish Takifugu exascurus is not approved for human consumption due to the lack of information on its toxicity. To clarify the toxicity of T. exascurus, ten live specimens were collected from the Sea of Kumano, Japan, and the toxicity and tetrodotoxin (TTX) concentration were determined using mouse bioassay and high performance liquid chromatography-fluorescence detection (HPLC-FLD), respectively. Read More