Tetrodotoxins lethality

Tetrodotoxin is one of the most powerful non-protein neurotoxins known. It occurs in the liver and ovaries of the Japanese puffer fish, Sphoerides rubripes and S. phyreus, and its lethal effects have been known for centuries, although it was isolated in crystalline form... 

Many urodeles produce irritating or even toxic secretions in their skin glands, and some are extremely toxic. The rough-skinned noNt Taricha granulosa) is the most toxic of newts from several genera. Its dorsal skin and ovarian eggs contain the very potent tetrodotoxin. Only 0.000 05 ml of newt skin is needed for a lethal peritoneal injection in mice. The skin of one newt can theoretically kill 25 000 mice. When bothered, the newt assumes a characteristic defense posture it arches, lifts its tail and releases an odor (Brodie etal., 1974). 

More recent studies have identified the most potent toxin produced by the frog as batrachotoxin (although it is one of about a hundred toxins). This is one of the most toxic substances known—five times more potent than tetrodotoxin, the toxin found in puffer fish (see pp. 252-3)—and a dose of 200 pg would be lethal for a human. Interestingly, tetrodotoxin is also found in the Californian newt. Batrachotoxin is secreted through the skin when the animal is stressed, and so when animals hck or bite the frog they are exposed to the toxin, which causes death by stopping the heart beating. 

Like the acetylcholine receptor channel, the sodium channel also was purified on the basis of its ability to bind a specific neurotoxin. Tetrodotoxin, an organic compound isolated from the puffer fish, binds to sodium channels with great avidity (K nM). The lethal dose of this poison for an adult human being is about 10 ng. The sodium channel was first purified from the electric organ of electric eel, which is a rich source of the protein forming this channel. The isolated protein is a single chain of 260 kd. 

That nature is not benign, indeed that it can be extremely deadly, is another lesson to take away from this section. While chemists have been successful in creating some highly lethal agents, none of these quite matches the likes of botulinum toxin, cobra venom or the poison in puffer fish (tetrodotoxin). 

Most toxic of the steroidal alkaloids present in the skin of dart-poison frogs, Phyllobates. Used as an arrow poison in western Colombia. Opens Na+ channels and depolarizes nerve fibres irreversible depolarization leading to paralysis ventricular fibrillation, cardiac and respiratory failure and death. Effect abolished by tetrodotoxin. Only toxic via damaged skin or digestive tract. Mice lethal at 2-3 pg/kg SC and 0.1 pg/kg IV. 

Marine toxins may be developed from marine organisms. Examples include saxitoxin, tetrodotoxin, palytoxin, brevetoxins, and microcystin. Saxitoxin is a sodium-channel blocker and is most toxic by inhalation compared to the other routes of exposure. Saxitoxin and tetrodotoxin are similar in mechanical action, toxicity, and physical attributes. They can be lethal within a few minutes when inhaled. It has not yet been chemically synthesized efficiently, or easily created in large quantities from natural sources. Palytoxin is produced from soft coral and is highly toxic. It is, however, difficult to produce or harvest from nature. 

Cases occur during all months of the year. It is not known whether the proportion of tetrodotoxic fish has increased. Simple incidence data would not necessarily answer this question since public health measures such as education and regulation of fugu chefs in Japan may effect incidence estimates regardless of changes in the proportion of animals containing toxin. In addition, it is possible that improved medical care has lowered the number of lethal cases. The retrospective analysis of 42 outbreaks of tetrodotoxin-associated paralytic snail poisoning in Asia found no temporal variation [140],... 

Saxitoxin. Some neurotoxins, such as saxitoxin and tetrodotoxin, can kill an individual very quickly after inhalation of a lethal dose (within minutes). These toxins act by blocking nerve conduction directly and cause death by paralyzing muscles of respiration. Yet, at just less than a lethal dose, the exposed individual may not even feel ill, or may only feel dizzy. 

Ciguatoxin (CTX 1) (formula see below). For structural elucidation 0.35 mg of C. (CeoHaeOg, Mr 1111.33) were isolated from 125 kg intestines of the moray Gymnothorax javanicus (primary origin Gambierdiscus toxicus). CTX acts as an agonist of voltage-sensitive sodium channels (VSSC). The lethal dose is 0.35 pg/kg (mouse). Thus, the toxin is about 100 times more potent than tetrodotoxin. 

The lethality of CTX (0.35 xg/kg) by intraperitoneal injection into mice is 280 times greater than that of tetrodotoxin (10 fxg/kg), which is a well-known non-polyether toxin from puffer fish. Orally, an amount as small as 70 ng of CTX can cause intoxication in humans. 

Chapter 8 focused on natural poisons and dealt with chemicals that were directly involved in the day-to-day arms race between species. A ratdesnake s venom, for example, has to neutralize a rodent so that the snake can have dinner. Toxins such as these have to be administered via a spine or a fang or a stinger. In other cases, the poison is not delivered, but rather lies within the animal s body, and exposure only occurs when a predator eats, or attempts to eat, the poisonous prey. The tissues of the blowfish, for example, are edible but contain tetrodotoxin, and extreme care in preparation is necessary lest the diner receive a potentially lethal dose of the neurotoxin. 

Tetrodotoxin has been isolated from various vertebrate and invertebrate species, among them from the blue-ringed octopus, Hapaloch-laena maculosa. Sheumack et al. (614) described the occurrence of a lethal toxin in the eggs of this species. The properties of this toxin were indistinguishable from those of authentic tetrodotoxin. 

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