Tetrodotoxin produced by Tetrodotoxin produced by PufferfishPufferfish

By Charles Brown

BiochemistryBiochemistry

•Binds to site 1 of the fast voltage gated sodium channel

•It blocks the Na+ current in human hearts and prevents contraction

Tetrodotoxin Tetrodotoxin

•Potent neurotoxinPotent neurotoxin

• Named after fish Named after fish Teratodoniformes = “four Teratodoniformes = “four toothed”toothed”

•Blocks Na+ channels on Blocks Na+ channels on surface of nerve surface of nerve membranesmembranes

•Found in more than just Found in more than just puffer fishpuffer fish

Production of TTXProduction of TTX The pufferfish does not create the The pufferfish does not create the

poison itself; rather it is generated poison itself; rather it is generated by various genera of bacteria within by various genera of bacteria within the fish. the fish.

The fish obtains the bacteria by The fish obtains the bacteria by eating food containing these eating food containing these bacteria. bacteria.

Pufferfish that are born and grown in Pufferfish that are born and grown in captivity do not produce tetrodotoxin captivity do not produce tetrodotoxin until they receive some of the until they receive some of the poison-producing bacteria.poison-producing bacteria.

Natural DefensesNatural Defenses Puffers use a combination of pectoral, Puffers use a combination of pectoral,

dorsal, anal, and caudal fins for dorsal, anal, and caudal fins for propulsion that make them highly propulsion that make them highly maneuverable but very slow, and maneuverable but very slow, and

therefore comparatively easy targets therefore comparatively easy targets for predators. for predators.

As a defense mechanism, puffers have As a defense mechanism, puffers have the ability to inflate rapidly, filling their the ability to inflate rapidly, filling their extremely elastic stomachs with water. extremely elastic stomachs with water. Thus, a hungry predator stalking the Thus, a hungry predator stalking the puffers may suddenly find itself facing puffers may suddenly find itself facing what seems to be a much larger fish what seems to be a much larger fish

and pause, giving the puffers an and pause, giving the puffers an opportunity to retreat to safety. opportunity to retreat to safety.

PoisonPoison•Extremely Potent

•1 milligram is lethal to an adult human

•LD50 for the mouse is 10 nanograms •100 times more lethal than black widow

• 10,000 times more lethal than cyanide

PoisonPoison• Stages of poisoning

1. Numbness of the lips and tongue • numbness in the face and extremities

• sensations of lightness or floating

2. Increasing paralysis • Some victims are unable to move, sitting may be

difficult.

• Increasing respiratory distress

• Speech is affected

3. Death usually occurs within 4 to 6 hours• Due to respiratory paralysis

TreatmentTreatment Provide prehospital care with careful attention Provide prehospital care with careful attention

to the airway.to the airway. Patients may require endotracheal intubation Patients may require endotracheal intubation

for oxygenation and airway protection in the for oxygenation and airway protection in the setting of muscle weakness and respiratory setting of muscle weakness and respiratory failure, which can occur soon after ingestion of failure, which can occur soon after ingestion of the tetrodotoxin.the tetrodotoxin.

Cardiac dysfunction may require IV intervention Cardiac dysfunction may require IV intervention with fluids, pressors, and antiarrhythmics.with fluids, pressors, and antiarrhythmics.

Severely poisoned patients may be very weak, Severely poisoned patients may be very weak, have difficulty speaking, and be unable to have difficulty speaking, and be unable to provide a history. Thus, clues from the provide a history. Thus, clues from the environment and bystanders are very important.environment and bystanders are very important.

DrugsDrugs•No drug has been shown to reverse the effects of tetrodotoxin poisoning. Treatment is symptomatic. Specific drug efficacy has only been documented anecdotally. •Anticholinesterase drugs (eg, neostigmine) have been proposed as a treatment option but have not been tested adequately.

Tetrodotoxin Tetrodotoxin HistoryHistory•Bacteriological/ Endosymbiotic

• Farmed Puffer fish do not produce TTX unless they are fed fed tissues of TTX producing fish

•Bacteria produce TTX for the Octopus

•Xanthid crabs contain TTX and paralytic shellfish toxin

•Puffer fish are immune to TTX due to mutation in Na+ channel receptors

Other TTX usesOther TTX uses•Anesthetics in Animals

•Prevention of damage to brain following stroke

•Suppressing pain in cancer patients

•Relieving the symptoms of withdrawal in opiate addicts

PufferfishPufferfish Pufferfish are considered one of the Pufferfish are considered one of the

most advanced group of bony fish. most advanced group of bony fish. Pufferfish have few bones, because Pufferfish have few bones, because

most of their bones in their head and most of their bones in their head and body, through time, have fused body, through time, have fused together together

Pufferfish skin is thick and feels Pufferfish skin is thick and feels leathery and is covered by scales that leathery and is covered by scales that have been modified into spines. have been modified into spines.

DistributionDistributionThe entire Tetraodontidae family The entire Tetraodontidae family has a worldwide distribution. Its has a worldwide distribution. Its members are found near-shore in members are found near-shore in shallow seas from the Atlantic to shallow seas from the Atlantic to the Pacific. Many members of the the Pacific. Many members of the family can be found in areas of family can be found in areas of

brackish waterbrackish water such as such as estuariesestuaries. . Some select species are known to Some select species are known to

exist entirely in freshwater. exist entirely in freshwater.

BreedingBreeding

Spawning can take place at any time Spawning can take place at any time during a day, year-round.during a day, year-round.

One-year old fish are already in the One-year old fish are already in the reproductive age. reproductive age.

Average fecundity—3000 eggs, Average fecundity—3000 eggs, maximum—about 6000. maximum—about 6000.

What does a Pufferfish What does a Pufferfish eat?eat?

A variety of small crustaceans. A variety of small crustaceans. Small fish Small fish SpongesSponges Sea Urchins Sea Urchins Owners of puffer fish in tropical Owners of puffer fish in tropical

aquariums report that their pets can aquariums report that their pets can be quite greedy, and seem to eat be quite greedy, and seem to eat anything! anything!

How Prepared/IngestedHow Prepared/Ingested

The first symptoms occur 15 minutes The first symptoms occur 15 minutes to several hours postingestion of to several hours postingestion of tetrodotoxin-containing food. A tetrodotoxin-containing food. A recent report on toxicity found that recent report on toxicity found that initial symptoms may occur up to 20 initial symptoms may occur up to 20 hours after ingestion. hours after ingestion.

How Prepared/IngestedHow Prepared/Ingested

Only specially licensed chefs can prepare and Only specially licensed chefs can prepare and sell fugu to the public.sell fugu to the public.

The consumption of the liver and ovaries is The consumption of the liver and ovaries is forbidden. forbidden.

Small amounts of the poison give a special Small amounts of the poison give a special desired sensation on the tongue, these parts desired sensation on the tongue, these parts are considered the most delicious by some are considered the most delicious by some gourmets. gourmets.

Every year a number of people die because Every year a number of people die because they underestimate the amount of poison in they underestimate the amount of poison in the consumed fish parts. the consumed fish parts.

StatisticsStatisticsIn the US: In the US: Reports of tetrodotoxin Reports of tetrodotoxin poisoning are rare in the US, but a poisoning are rare in the US, but a 1996 report in the 1996 report in the Morbidity and Morbidity and Mortality Weekly Report (MMWR)Mortality Weekly Report (MMWR) documents 3 cases of tetrodotoxin documents 3 cases of tetrodotoxin

toxicity from persons ingesting toxicity from persons ingesting contaminated fugu imported by a contaminated fugu imported by a

coworker from Japan. coworker from Japan. Internationally: Internationally: Despite the careful Despite the careful

training and certification of fugu chefs training and certification of fugu chefs in Japan, cases of mortality and in Japan, cases of mortality and

morbidity from puffer fish ingestion morbidity from puffer fish ingestion continue to be reported. Estimates vary, continue to be reported. Estimates vary,

but up to 50 deaths may occur each but up to 50 deaths may occur each year from tetrodotoxin poisoning in year from tetrodotoxin poisoning in

Japan. Japan.

TriviaTrivia Dolphins have been observed using puffers Dolphins have been observed using puffers

as a sort of toy in the wild. They tease the as a sort of toy in the wild. They tease the puffers with their teeth, causing the small puffers with their teeth, causing the small fish to become alarmed and then inflate.fish to become alarmed and then inflate.

When lifted out of water, puffers can inflate When lifted out of water, puffers can inflate with air, but they may have problems with air, but they may have problems deflating again afterwards. When this deflating again afterwards. When this happens with aquarium specimens, happens with aquarium specimens, fishkeepers hold the puffer underwater by fishkeepers hold the puffer underwater by the tail, head upwards, and shake the fish the tail, head upwards, and shake the fish gently until the air escapes out of the mouth. gently until the air escapes out of the mouth.

ReferencesReferencesFroese, R. and D. Pauly. Editors.. Froese, R. and D. Pauly. Editors..

448 Family Tetraodontidae - Puffers448 Family Tetraodontidae - Puffers. FishBase. . FishBase. Retrieved on Retrieved on 20072007-02-10 -02-10

Arreola, V.I., and M.W. Westneat. 1996. Mechanics Arreola, V.I., and M.W. Westneat. 1996. Mechanics of propulsion by multiple fins: kinematics of aquatic of propulsion by multiple fins: kinematics of aquatic locomotion in the burrfish (Chilomycterus schoepfi). locomotion in the burrfish (Chilomycterus schoepfi). Proceedings of the Royal Society of London B 263: Proceedings of the Royal Society of London B 263:

1689–1696. 1689–1696. Ebert, Klaus (2001): The Puffers of Fresh and Ebert, Klaus (2001): The Puffers of Fresh and Brackish Water, Aqualog, ISBN 393170260X. Brackish Water, Aqualog, ISBN 393170260X.

Gordon, M.S., Plaut, I., and D. Kim. 1996. How Gordon, M.S., Plaut, I., and D. Kim. 1996. How puffers (Teleostei: Tetraodontidae) swim. Journal of puffers (Teleostei: Tetraodontidae) swim. Journal of

Fish Biology 49: 319–328. Fish Biology 49: 319–328. Plaut, I. and T. Chen. 2003. How small puffers Plaut, I. and T. Chen. 2003. How small puffers

(Teleostei: Tetraodontidae) swim. Ichthyological (Teleostei: Tetraodontidae) swim. Ichthyological Research 50: 149–153. Research 50: 149–153.