Transcript Tetrodotoxin and Maculotoxin

Tetrodotoxin and
Maculotoxin
Skye King and Azadeh Fotouhie
Outline
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Molecular Discussion of Tetrodotoxin and Maculotoxin
Biochemistry of Tetrodotoxin and Maculotoxin
Origin, Habitat, and Geographical Distribution
Scenario: Blue-Ringed Octopus vs. Diver
Tetrodotoxin Poisoning and Mechanism
Maculotoxin Poisoning and Mechanism
Symptoms of Tetrodotoxin and Maculotoxin Poisoning
Treatment of TTX and Maculotoxin poisoning
Sources
Tetrodotoxin: Structure
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C11H17N3O8
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Tetrodotoxin is a solid,
colorless crystal, and a
potent poison or toxin.
When heated above 428° F,
the solid darkens.
It is also known as
anhydrotetrodotoxin 4epitetrodotoxin, or
tetrodonic acid.
LD50: 5.0-8.0 μg/kg
Molecular mass: 319.28 u
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Maculotoxin
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Maculotoxin is the venom version of
tetrodotoxin. They are both highly toxic to
animals and to humans and target the
neural pathway. The effects of maculotoxin
have been found to be identical to those of
tetrodotoxin and are mentioned
interchangeably by researchers for the
purposes of discussion.
Have different sources in nature
Biochemistry of Tetrodotoxin and
Maculotoxin
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TTX and Maculotoxin are known as neurotoxins; target
sodium channels in neurons
Because of the shape of the molecule, it can perfectly plug
the opening of the ion channels located on the neurons,
prevented ion flow; structure fits function
Bind to Site 1 of the voltage-gated Na+ channel in neurons.
The Na+ channel becomes temporarily non-functional
No Na+ influx into the cell; no action potentials produced and
transferred to other neurons or cells in the body; no
information transfer
Other toxins like saxitoxin and conotoxin bind to this site as
well
Voltage-Gated Na+ Channel
TTX and Maculotoxin bind to the lumen of the Na+ channel (extracellular
side) and prevent sodium influx into the cell. From
http://openwetware.org/wiki/BIO254:AP
Biochemistry of Tetrodotoxin and
Maculotoxin
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Due to extensive studies of tetrodotoxin
and maculotoxin, two types of voltagegated Na+ channels have been discovered
in humans:
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Tetrodotoxin-sensitive channels: TTX and
maculotoxin bind to this site with an affinity of 5-15
nanomolar.
Tetrodotoxin-resistant channels: TTX and
maculotoxin bind to this site with significantly
lower affinity
Biochemistry of Tetrodotoxin and
Maculotoxin
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Tetrodotoxin-sensitive channels are found
throughout the body and in central nervous
system
Tetrodotoxin-resistant channels are found
in neurons located in the cardiac tissue
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Sources of Tetrodotoxin and
Maculotoxin
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Tetrodotoxin can be found in various animal species: western
newts (Taricha), parrotfish, toads (Atelopus), certain starfish,
certain angelfish, Chaetognatha, nemerteans, xanthid crabs,
pufferfish, poison arrow frogs, and flatworms. It is usually
found in specific parts or tissues of the organisms. For
example, in pufferfish, TTX is found in high concentrations in
the gonads, liver, intestines, and skin.
Maculotoxin is the venom version of tetrodotoxin and it is
found in the salivary glands of the blue-ringed octopus
(Hapalochlaena)
Sources of Tetrodotoxin and
Maculotoxin
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The toxicity of the compounds depends on
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Species in which it is found and species which is
victimized
Different seasons
Different geographic locations
The individual organism carrying the toxin
A typical scenario of maculotoxin
poisoning……..
…….It was in the midst of summer, and the sun glimmered upon
ocean surface as the group of scuba divers explored the
hidden depths. It was then that the young, adventurous diver
strayed too far from the group. He had noticed something in
the distance….a strange octopus he had never before
seen….
…….as foolishness grasps him and ignorance sparkles in his
eyes, he decides to capture this octopus and show it to his
fellow scuba divers….he smiles with triumph as he traps it
between his hand and a rock jutting out of the ground.
Reaching forth to grab it, he feels the octopus brush against
his hand and sees a drop of blood dissipate into the water…..
A typical scenario of maculotoxin
poisoning……..continued.
…realizing he has been bitten by the octopus, panicstricken he looks around for the others, in vain….he
attempts to swim to the surface to find his fellow divers,
only to realize that he has drifted too far from the
group…..
….As the toxin begins to set in, unbeknownst to him, he
feels the urge to swim somewhere, anywhere, to rest
and ease his weak limbs….the journey to shore is a
difficult one. Numb, weak, and almost paralyzed, he
reaches safety….safety from the outside world; inside,
he is dying….
Tetrodotoxin Poisoning
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Tetrodotoxin poisoning can occur through
eating fish that is improperly prepared, or
through the contamination of other food
products.
A common reason for tetrodotoxin
poisoning is the consumption of the
pufferfish, which contains very high levels
of the toxin in its skin and internal organs.
Tetrodotoxin Poisoning
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Pufferfish contains enough tetrodotoxin in its skin
and organs to cause death in those that consume
it; samples of pufferfish contain from 0.5 to 30 mg
of tetrodotoxin per kg of wet tissue (LD50 is 5.08.0 μg/kg).
In Japan, specially trained and licensed chefs
prepare a traditional dish served at special
restaurants, called fugu. Fugu is prepared from
pufferfish, with small amounts of tetrodotoxin in it
to cause slight symptoms of tingling and
numbness, without causing serious symptoms.
Fugu in Japan
Fugu is a traditional dish of carefully prepared pufferfish, considered a
delicacy in Japan
Tetrodotoxin Poisoning
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The first noted case of TTX poisoning is known to have
occurred on the ship of Captain James Cook. It is recorded
that his crew ate a local tropical fish and fed the remains to
the pigs on the ship. The morning after that, the crew
members were all inflicted with symptoms of tetrodotoxin
poisoning and all of the pigs were found dead. Clearly, the
remains that were given to the pigs contained high
concentrations of tetrodotoxin and killed them.
Tetrodotoxin was first isolated in 1909 by the Japanese
scientist, Dr. Yoshizumi Tahara.
TTX is common in pufferfish of the Atlantic Ocean , Gulf of
Mexico, and Gulf of California.
Maculotoxin Poisoning
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Maculotoxin is found mostly in the blue-ringed octopus.
This octopus has two poison glands that can secrete poison
into the saliva. One type is used to obtain food and is
effective in capturing crabs as prey; the other is extremely
toxic and is known as maculotoxin.
When threatened, the octopus uses this toxin as a defense
mechanism. The main method of poisoning humans and
other animals is not very well known. We are unsure as to
whether it is through the bite, or mere secretion that the
octopus defends itself.
Maculotoxin Poisoning
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The blue-ringed octopus warns its predator when
it is ready to attack. It has blue rings on its skin,
which have evolved a symbiotic relationship with
the maculotoxin-producing bacteria that live in the
salivary glands of the octopus. The bacteria make
use of the good living conditions and, in turn,
produce a toxin to help the octopus defend itself.
The blue rings of the octopus change shape and
flash to warn predators of their danger.
Maculotoxin Poisoning
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An adult blue-ringed octopus weighing 25 g has enough toxin
to paralyze and kill 10 adult humans.
Due to this reputation, they are being killed by fearful
humans.
In other cases, in Australia, world-leading venom industries
harvest the octopus to make use of its venom.
This raises concern about the possible increase in casualties
due to the increasing interaction between humans and the
octopus; in addition, members of the blue-ringed octopus
species are decreasing with time.
Symptoms and Effects of Tetrodotoxin
and Maculotoxin Poisoning
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One significant effect that the blockage of
the Na+ channel has on the body is that
when Na+ does not enter the contractile
cells of the heart, or myocytes, the heart
can no longer contract as it should. This
paralysis of the myocytes causes death in
the individual poisoned.
Symptoms and Effects of Tetrodotoxin
and Maculotoxin Poisoning
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Once the Na+ channel is blocked by the
toxin, action potentials can no longer be
produced and information does not travel
between the CNS and the body. Hence,
paralysis of muscles occurs, followed by a
multitude of symptoms.
Symptoms and Effects of Tetrodotoxin
and Maculotoxin Poisoning
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During the First Stage of Poisoning:
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Numbness, paresthesia (tingling of lips and
tongue), facial paresthesia, extremity paresthesia
and numbness, headache, light-headedness,
feeling that one is floating, sweating, dizziness,
salivation, vomiting, nausea, diarrhea, abdominal
pain, motor dysfunction, weakness, speech
difficulty
Typically starts 15-30 minutes after exposure to
the toxin, but can be delayed up to four hours
Symptoms and Effects of Tetrodotoxin
and Maculotoxin Poisoning
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During the Second Stage of Poisoning:
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Increased paralysis throughout body, paralysis in
respiratory muscles, difficulty breathing,
abnormal heart rhythms, hypotension, fixed and
dilated pupils, coma, seizures, respiratory arrest,
death.
Death can even occur 20 minutes after exposure,
or 24 hours after exposure. Usually the second
stage symptoms are seen in the firs 4-8 hours
Treatment
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There is no antidote for tetrodotoxin or
maculotoxin due to the quick action and
high binding affinities of the toxins
Therapy is mostly supportive for
tetrodotoxin poisoning. Respiratory support
is essential and must be implemented; in
addition, alpha adrenergic agonists and
intravenous fluids can combat hypotension.
Treatment
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After being bitten by the blue-ringed octopus,
pressure must be applied to the wound and
rescue breathing must be given and continued
until the victim can breathe again.
In the hospital, the toxin can be washed out while
giving respiratory assistance. Children are more
susceptible and thus must be given medical
attention first. Victims that can live through the
first 24 hours usually recover completely.
Sources
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Chew, S.K., Goh, C.H., Wang, K.W., Mah, P.K., and Tan, B.Y. 1983. Pufferfish (Tetrodotoxin) Poisoning:
Clinical Report and Role of Anti-cholinesterase in Therapy. Singapore Medical Journal. 24(3): 168-171.
Ahasan, H.A.M.N., Mamun, A.A., Karim, S.R., Bakar, M.A., Gazi, E.A., and Bala, C.S. 2004. Paralytic
Complications of Pufferfish (Tetrodotoxin) Poisoning. Singapore Medical Journal. 45(2): 73.
Freeman, S.E. and Turner, R.J. 1970. Maculotoxin, A Potent Toxin Secreted by Octopus Maculosis
Hoyle. Toxicol. Appl. Pharmacol. 16(3): 681-690.
Dulhunty, A. and Gage, P.W. 1971. Selective Effects of An Octopus Toxin on Action Potentials. Journal of
Physiology. 218(2): 433-445.
1. Xanthid Crab: <http://www.hawaiisfishes.com/inverts/true_crabs/red_crab-Tina.jpg>
2. Starfish: http://www7.nationalgeographic.com/ngm/0505/feature1/online_extra.html
3. Parrotfish: http://www.junglewalk.com/animal-pictures/660/Parrotfish-12636.jpg
4. Blue Poison Arrow Frog:
http://www.livingunderworld.org/anura/database/dendrobatidae/dendrobates/auratus/index.shtml
5. Chaetognatha: <http://artikler.uwphoto.no/100/esv080cd16.jpg
6. Wesern Newt: http://www.livingunderworld.org/caudata/database/salamandridae/taricha/
7. Blue-ringed Octopus: <http://helium.vancouver.wsu.edu/~lindblad/blueringedoctopus.html>