Tetrodotoxin Toxicity

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Background
Poisoning with the neurotoxin tetrodotoxin (TTX) occurs after ingestion of various species of puffer fish (see the image below).
Puffer fish.
The flesh of the puffer fish (ie, fugu) is considered a delicacy in Japan. It is prepared by chefs specially trained and certified by the government to prepare the flesh free of the toxic liver, gonads, and skin. Despite these precautions, many cases of tetrodotoxin poisoning are reported each year in patients ingesting fugu.
Poisonings usually occur after eating fish caught and prepared by uncertified handlers.
The toxic dose is not clear because puffer fish have different concentrations of tetrodotoxin. A dose of 1-2 mg of purified toxin can be lethal. Reported cases from the Centers for Disease Control and Prevention (CDC) have documented toxicity with ingestion of as little as 1.4 ounces of puffer fish.
Tetrodotoxin also is found in the the following:
• Gastropod mollusc
• The eggs of horseshoe crabs
• Newts of the genus Taricha
• The skin of Atelopid frogs
• The skin and viscera of porcupine fish, globefish, balloon fish, blowfish, sunfish, toadfish, blue-ringed octopus, and some species of salamanders
Pathophysiology
Puffer fish contain the potent neurotoxin tetrodotoxin. TTX is thought to be synthesized by a bacterial or dinoflagellate species associated with the puffer fish.
The toxin is concentrated in the liver, gonads, and skin. The level of toxicity is seasonal, and, in Japan, fugu is served only from October through March.
Tetrodotoxin is a heat-stable (except in alkaline environments) and water-soluble nonprotein.
It is a heterocyclic, small, organic molecule that acts directly on the electrically active sodium channel in nerve tissue (see the image below).
Chemical structure of tetrodotoxin.
Tetrodotoxin blocks diffusion of sodium through the sodium channel, thus preventing depolarization and propagation of action

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