Download Tetrodotoxin

Tetrodotoxin produced by
Pufferfish
By Charles Brown
Biochemistry
•Binds to site 1 of the fast voltage gated sodium
channel
•It blocks the Na+ current in human hearts and
prevents contraction
Tetrodotoxin
•Potent neurotoxin
• Named after fish
Teratodoniformes = “four
toothed”
•Blocks Na+ channels on
surface of nerve membranes
•Found in more than just
puffer fish
Production of TTX
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The pufferfish does not create the poison
itself; rather it is generated by various genera
of bacteria within the fish.
The fish obtains the bacteria by eating food
containing these bacteria.
Pufferfish that are born and grown in
captivity do not produce tetrodotoxin until
they receive some of the poison-producing
bacteria.
Natural Defenses
Puffers use a combination of pectoral, dorsal,
anal, and caudal fins for propulsion that make them
highly maneuverable but very slow, and therefore
comparatively easy targets for predators.
 As a defense mechanism, puffers have the ability
to inflate rapidly, filling their extremely elastic
stomachs with water.
 Thus, a hungry predator stalking the puffers may
suddenly find itself facing what seems to be a much
larger fish and pause, giving the puffers an
opportunity to retreat to safety.

Poison
•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
Poison
• 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
Treatment
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Provide prehospital care with careful attention to the
airway.
Patients may require endotracheal intubation for
oxygenation and airway protection in the setting of
muscle weakness and respiratory failure, which can
occur soon after ingestion of the tetrodotoxin.
Cardiac dysfunction may require IV intervention with
fluids, pressors, and antiarrhythmics.
Severely poisoned patients may be very weak, have
difficulty speaking, and be unable to provide a history.
Thus, clues from the environment and bystanders are
very important.
Drugs
•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 History
•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 uses
•Anesthetics in Animals
•Prevention of damage to brain following stroke
•Suppressing pain in cancer patients
•Relieving the symptoms of withdrawal in opiate
addicts
Pufferfish
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Pufferfish are considered one of the most
advanced group of bony fish.
Pufferfish have few bones, because most of their
bones in their head and body, through time, have
fused together
Pufferfish skin is thick and feels leathery and is
covered by scales that have been modified into
spines.
Distribution
The entire Tetraodontidae family has a
worldwide distribution. Its members are
found near-shore in shallow seas from the
Atlantic to the Pacific. Many members of the
family can be found in areas of brackish
water such as estuaries. Some select species
are known to exist entirely in freshwater.
Breeding
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Spawning can take place at any time during
a day, year-round.
One-year old fish are already in the
reproductive age.
Average fecundity—3000 eggs, maximum—
about 6000.
What does a Pufferfish eat?
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A variety of small crustaceans.
Small fish
Sponges
Sea Urchins
Owners of puffer fish in tropical aquariums
report that their pets can be quite greedy, and
seem to eat anything!
How Prepared/Ingested
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The first symptoms occur 15 minutes to several
hours postingestion of tetrodotoxin-containing
food. A recent report on toxicity found that
initial symptoms may occur up to 20 hours after
ingestion.
How Prepared/Ingested
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Only specially licensed chefs can prepare and sell fugu
to the public.
The consumption of the liver and ovaries is forbidden.
Small amounts of the poison give a special desired
sensation on the tongue, these parts are considered the
most delicious by some gourmets.
Every year a number of people die because they
underestimate the amount of poison in the consumed
fish parts.
Statistics
In the US: Reports of tetrodotoxin poisoning are
rare in the US, but a 1996 report in the Morbidity and
Mortality Weekly Report (MMWR) documents 3 cases
of tetrodotoxin toxicity from persons ingesting
contaminated fugu imported by a coworker from
Japan.
Internationally: Despite the careful training and
certification of fugu chefs in Japan, cases of
mortality and morbidity from puffer fish ingestion
continue to be reported. Estimates vary, but up to
50 deaths may occur each year from tetrodotoxin
poisoning in Japan.
Trivia
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Dolphins have been observed using puffers as a sort of
toy in the wild. They tease the puffers with their teeth,
causing the small fish to become alarmed and then
inflate.
When lifted out of water, puffers can inflate with air,
but they may have problems deflating again afterwards.
When this happens with aquarium specimens,
fishkeepers hold the puffer underwater by the tail, head
upwards, and shake the fish gently until the air escapes
out of the mouth.
References
Froese,
R. and D. Pauly. Editors.. 448 Family Tetraodontidae Puffers. FishBase. Retrieved on 2007-02-10
Arreola, V.I., and M.W. Westneat. 1996. Mechanics of propulsion by
multiple fins: kinematics of aquatic locomotion in the burrfish
(Chilomycterus schoepfi). Proceedings of the Royal Society of
London B 263: 1689–1696.
Ebert, Klaus (2001): The Puffers of Fresh and Brackish Water,
Aqualog, ISBN 393170260X.
Gordon, M.S., Plaut, I., and D. Kim. 1996. How puffers (Teleostei:
Tetraodontidae) swim. Journal of Fish Biology 49: 319–328.
Plaut, I. and T. Chen. 2003. How small puffers (Teleostei:
Tetraodontidae) swim. Ichthyological Research 50: 149–153.