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12 pages, 1968 KiB

Open AccessArticle

Levels of Tetrodotoxins in Spawning Pufferfish, Takifugu alboplumbeus

by Masaki Asano, Chihiro Ishizaki, Taiga Tomonou, Masato Kihara, Masaaki Ito, Shino Yasukawa, Kyoko Shirai, Hikaru Oyama, Shin Izawa, Reona Kawamura, Kanae Saito, Rei Suo, Ryota Nakahigashi, Masaatsu Adachi, Toshio Nishikawa, Haruo Sugita and Shiro Itoi

Mar. Drugs 2023, 21(4), 207; https://doi.org/10.3390/md21040207 - 25 Mar 2023

Cited by 4 | Viewed by 3143

Abstract

Tetrodotoxin (TTX), also known as pufferfish toxin, is an extremely potent neurotoxin thought to be used as a biological defense compound in organisms bearing it. Although TTX was thought to function as a chemical agent for defense and anti-predation and an attractant for TTX-bearing animals including pufferfish, it has recently been demonstrated that pufferfish were also attracted to 5,6,11-trideoxyTTX, a related compound, rather than TTX alone. In this study, we attempted to estimate the roles of TTXs (TTX and 5,6,11-trideoxyTTX) in the pufferfish, Takifugu alboplumbeus, through examining the location of TTXs in various tissues of spawning pufferfish from Enoshima and Kamogawa, Japan. TTXs levels in the Kamogawa population were higher than those in the Enoshima population, and there was no significant difference in the amount of TTXs between the sexes in either population. Individual differences were greater in females than in males. However, the location of both substances in tissues differed significantly between sexes: male pufferfish accumulated most of their TTX in the skin and liver and most of their 5,6,11-trideoxyTTX in the skin, whereas females accumulated most of their TTX and 5,6,11-trideoxyTTX in the ovaries and skin. Full article

(This article belongs to the Special Issue Tetrodotoxins: Detection, Biosynthesis and Biological Effects)

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15 pages, 6570 KiB

Open AccessReview

Tetrodotoxin: A New Strategy to Treat Visceral Pain?

by Ana Campos-Ríos, Lola Rueda-Ruzafa, Salvador Herrera-Pérez, Paula Rivas-Ramírez and José Antonio Lamas

Toxins 2021, 13(7), 496; https://doi.org/10.3390/toxins13070496 - 16 Jul 2021

Cited by 5 | Viewed by 6242

Abstract

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. Full article

(This article belongs to the Special Issue Tetrodotoxin (TTX) as a Therapeutic Agent)

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20 pages, 1388 KiB

Open AccessArticle

Safety, Tolerability, Pharmacokinetics, and Concentration-QTc Analysis of Tetrodotoxin: A Randomized, Dose Escalation Study in Healthy Adults

by Mojgan Kavoosi, Terry E. O’Reilly, Mehran Kavoosi, Peng Chai, Caroline Engel, Walter Korz, Christopher C. Gallen and Robert M. Lester

Toxins 2020, 12(8), 511; https://doi.org/10.3390/toxins12080511 - 9 Aug 2020

Cited by 13 | Viewed by 7282

Abstract

Tetrodotoxin (TTX) is a highly specific voltage-gated sodium channel (VGSC) blocker in clinical evaluation as a peripheral-acting analgesic for chronic pain. This study presents the first published results of the safety including cardiac liability of TTX at therapeutic-relevant concentrations in twenty-five healthy adults. Randomized, double-blind, placebo-, and positive- (moxifloxacin) controlled study evaluated single ascending doses of 15 µg, 30 µg, and 45 µg TTX over 3 periods with a 7-day washout between each period. Subcutaneous injections of TTX were readily absorbed, reaching maximum plasma concentration (C_max) within 1.5 h. Both extent of exposure (AUC) and C_max increased in proportion to dose. No QT prolongation was identified by concentration-QTc analysis and the upper bounds of the two-sided 90% confidence interval of predicted maximum baseline and placebo corrected QTcF (ΔΔQTcF) value did not exceed 10 ms for all tetrodotoxin doses, thereby meeting the criteria of a negative QT study. Safety assessments showed no clinically relevant changes with values similar between all groups and no subject withdrawing due to adverse events. Paresthesia, oral-paresthesia, headache, dizziness, nausea, and myalgia were the most common TEAEs (overall occurrence ≥5%) in the TTX treatment groups. TTX doses investigated in this study are safe, well-tolerated, and lack proarrhythmic proclivity. Full article

(This article belongs to the Special Issue Tetrodotoxin (TTX) as a Therapeutic Agent)

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23 pages, 423 KiB

Open AccessReview

Tetrodotoxin – Distribution and Accumulation in Aquatic Organisms, and Cases of Human Intoxication

by Tamao Noguch and Osamu Arakawa

Mar. Drugs 2008, 6(2), 220-242; https://doi.org/10.3390/md6020220 - 28 May 2008

Cited by 350 | Viewed by 28287

Abstract

Many pufferfish of the family Tetraodontidae possess a potent neurotoxin, tetrodotoxin (TTX). In marine pufferfish species, toxicity is generally high in the liver and ovary, whereas in brackish water and freshwater species, toxicity is higher in the skin. In 1964, the toxin of the California newt was identified as TTX as well, and since then TTX has been detected in a variety of other organisms. TTX is produced primarily by marine bacteria, and pufferfish accumulate TTX via the food chain that begins with these bacteria. Consequently, pufferfish become non-toxic when they are fed TTX-free diets in an environment in which the invasion of TTX-bearing organisms is completely shut off. Although some researchers claim that the TTX of amphibians is endogenous, we believe that it also has an exogenous origin, i.e., from organisms consumed as food. TTX-bearing animals are equipped with a high tolerance to TTX, and thus retain or accumulate TTX possibly as a biologic defense substance. There have been many cases of human intoxication due to the ingestion of TTX-bearing pufferfish, mainly in Japan, China, and Taiwan, and several victims have died. Several cases of TTX intoxication due to the ingestion of small gastropods, including some lethal cases, were recently reported in China and Taiwan, revealing a serious public health issue. Full article

(This article belongs to the Special Issue Marine Toxins)

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