1. The Poisonous Puffer Fish
Reported by:
Austria, Princess Erbie C.
BSEd Physics 3A
“Do not eat me”
S.Y. 2012-2013

2. The Poisonous Puffer Fish
Duality in nature is a peculiar thing. More often than not,
bright beautiful colors are often nature's way of saying "I
am poisonous, stay away, do not eat me!". Most predators
know this and keep their distance, giving wide berth to such
organisms, save one: The Most Successful Predator on this
Planet. Man. Even the most successful predator on this
planet has its moments. 100-200 of people become ill
each year after eating "fugu", or pufferfish each
year. Roughly half of these intoxifications are fatal, even
with immediate treatment.(Dr. Chein-Yuan Kao, Brooklyn
Medical Center)

3. IUPAC name
(4R,4aR,5R,6S,7S,8S,8aR,10S,12S)-2-azaniumylidene-4,6,8,12-tetrahydroxy-6-
(hydroxymethyl)-2,3,4,4a,5,6,7,8-octahydro-1H-8a,10-methano-5,7-
(epoxymethanooxy)quinazolin-10-olate

4. Other names
anhydrotetrodotoxin, 4-epitetrodotoxin, tetrodonic acid, TTX

5. Anhydrotetrodotoxin 4-epitetrodotoxin, or Tetrodotoxin, as it
is more easily referred to, is 10,000 times more lethal than
cyanide. It is perhaps the most potent toxin present in
nature, save two others, which occur in
bacteria. (Light,1998) Tetrodotoxin is present in a other
animals besides pufferfish, with the blue-ringed octopus,
harlequin frogs, and rough-skinned newts making the
list. Tetrodotoxin has even been isolated from certain strains
of algae, along with more marine life such as some snails,
crabs and even a type of flatworm. While tetrodotoxin is not
exclusively owned by just pufferfish, our chances of coming
into contact with this poison is surely greater with them.
Tetrodotoxin affects the nervous system in such a way as to
prevent the propagation of nerve impulses. While it does
not cross the blood-brain barrier, it inhibits the ability of our
nerves to send messages to other parts of our body.

7. Confused? Here's how it works. We all use electrical impulses to send
messages from our brain to other parts of our body to tell them to do
things (yes, I knew you knew that, but I had to start
somewhere). These messages fire from dendrite to axon within the
nerve cells, ultimately reaching their destination, in this case a muscle
fiber (such as in the heart). The "messages" involve the passage of
sodium (Na+) ions and potassium (K+) ions across the axon, along the
nerve cell membrane. All you really need to understand is that your
nerves need both of these ions to produce the electrical messages
(action potentials). Ultimately, this sends the right message to the
muscle fiber shown in the diagram here. Now, you have these two ions
running up and down the cell interacting with only each other and the
cell membrane (simply put). Sodium and potassium are moving in and
out of the cell membrane (like the "skin" of the axon) causing changes
and carrying the electrical message. Again, your body needs both of
them in order to get the signal across. Tetrodotoxin binds itself to the
sodium ion, preventing it from moving in and out of the membrane. As
you can guess, this pretty much shuts down the entire "message-
sending" process, and the impulse never gets to its destination. Now,
knowing that we really need to do this (you said you did earlier, right?)
you can imagine what tetrodotoxin would do to us if it got into really
vital nerve cells.

8. Here are some actual nerve cells. This image was taken from an electron
microscope observing stained nerve cells. A little tetrodotoxin and... well, you
get the picture. Actually, let's describe some of the symptoms of fugu
poisoning. So let's say your sushi chef had a little too much sake the night
before and goofed a bit while preparing your meal of pufferfish--
The first signs that something is awry is a slight numbness in the lips and
tongue (the sodium ions can't carry the messages, remember?). This
numbness soon increases and spreads to certain parts of your face and
throat. Some reported initial symptoms also included involuntary muscle
spasms, weakness, dizziness, and loss of speech.(2001,mednets.org) There is
excessive salivation and sweating, along with slowed heart rate and a drop in
body temperature. Victims soon experience respiratory distress, marked by
rapid, shallow breathing. The secondary stage of the poisoning involves
increased paralysis, to the point where even sitting becomes difficult. From this
point on it's pretty much downhill. After another increase in paralysis, mental
impairment and convulsions (yes, probably in that order) ensue. This is
followed by an inevitable case of cardiac arrhythmia. Wait! It's not over
yet. Do you remember earlier when I mentioned that tetrodotoxin doesn't cross
the brain-blood barrier? This basically means that your brain, although
composed of nerve cells, is not directly affected by this toxin. There have been
reports of fugu poisoning survivors that they were completely lucid during the
entire event, finally recovering to tell the tale. (M. Lester, 1996)

9. http://puffernet.tripod.com/tetrodotoxin.html
This may come as no surprise to you voodoo enthusiasts out
there (funny to see you guys in the LFS buying shrimp and
bloodworms), since your voodoo zombie master (no disrespect, I
don't know what else to call you?) uses tetrodotoxin in his
zombie powder. Yes, it's true, this toxin is the main ingredient in
zombie making practices in Haiti and West Africa. (Light,
1998) (If you're a zombie or just want more information, go to
google.com and search "Clarvius Narcisse", a zombie case
documented by ethnobotonists.)
But I digress--
Death usually occurs within 4 to 6 hours, with a known range of
about 20 minutes to 8 hours. If you've survived this ordeal,
consider yourself lucky. Since there is no antidote, medical
professionals are left with no alternative but to treat the
symptoms. This is accomplished by removing remaining toxins
in your stomach with a charcoal lavage and techniques involving
life-support in an artificial respirator.
Let me reiterate, bright colors usually mean "do not eat me".

10. A puffer fish with its body inflated.

11. Poisoning
 TTX is extremely toxic. The toxin can enter the body by ingestion,
injection, inhalation and through abraded skin.. The mechanism of
toxicity is through the blockage of fast voltage-gated sodium
channels. These are required for the normal transmission of
signals between the body and brain, as a result, TTX causes
paralysis of voluntary muscles (including the diaphragm, stopping
breathing), the loss of vagal regulation of heart rate (causing it to
increase to around 100bpm), and loss of sensation.
 TTX is roughly 100 times more poisonous than potassium
cyanide. Fish poisoning by consumption of members of the
order Tetraodontiformes is extremely serious. The organs (e.g.
liver) of the pufferfish can contain levels of tetrodotoxin sufficient to
produce paralysis of the diaphragm and, through this mechanism,
death due to respiratory failure.. Toxicity varies between species
and at different seasons and geographic localities, and the flesh of
many pufferfish may not be dangerously toxic. It is not always fatal;
but at near-lethal doses, it can leave a person in a state of near-
death for several days, while the person remains conscious.

12.  For this reason, TTX has been alleged an
ingredient in Haitian Vodou and the closest
approximation of zombieism, an idea popularized
by Harvard-trained ethnobotanist Wade Davis in
a 1983 paper, and in his 1985 book, The Serpent
and the Rainbow. This idea was dismissed by
the scientific community in the 1980s, as the
descriptions of voodoo zombies do not match the
symptoms displayed by victims of tetrodotoxin
poisoning, and the alleged incidents of zombies
created in this manner could not be
substantiated.

13. Symptoms and treatment
 The diagnosis of pufferfish poisoning is based on the
observed symptomology and recent dietary history.
 Symptoms typically develop within 30 minutes of
ingestion, but may be delayed by up to four hours;
however, death once occurred within 17 minutes of
ingestion. Paresthesia of the lips and tongue is followed
by sialorrhea, sweating, headache, weakness,
lethargy, incoordination, tremor,
paralysis, cyanosis, aphonia, dysphagia,
seizures, dyspnea, bronchorrhea, bronchospasm,
respiratory failure, coma, and hypotension. Gastroenteric
symptoms are often severe and include nausea,
vomiting, diarrhea, and abdominal pain. Cardiac
arrhythmias may precede complete respiratory failure
and cardiovascular collapse.

14.  The first symptom of intoxication is a slight numbness of
the lips and tongue, appearing between 20 minutes to
three hours after eating poisonous pufferfish. The next
symptom is increasing paresthesia in the face and
extremities, which may be followed by sensations of
lightness or floating.
Headache, epigastric pain, nausea, diarrhea,
and/or vomiting may occur. Occasionally, some reeling or
difficulty in walking may occur. The second stage of the
intoxication is increasing paralysis. Many victims are
unable to move; even sitting may be difficult. There is
increasing respiratory distress. Speech is affected, and
the victim usually exhibits dyspnea, cyanosis,
and hypotension. Paralysis increases and convulsions,
mental impairment, and cardiac arrhythmia may occur.
The victim, although completely paralyzed, may be
conscious and in some cases completely lucid until
shortly before death. Death usually occurs within 4 to 6
hours, with a known range of about 20 minutes to 8

15.  If the patient survives 24 hours, recovery without any
residual effects will usually occur over several days.
Therapy is supportive and based on symptoms, with
aggressive early airway management. If ingested,
treatment can consist of emptying the stomach, feeding
the victim activated charcoal to bind the toxin, and taking
standard life-support measures to keep the victim alive
until the effect of the poison has worn off. Alpha
adrenergic agonists are recommended in addition to
intravenous fluids to combat
hypotension. Anticholinesterase agents have been used
with mixed success. No antidote has been developed
and approved for human use; but a monoclonal antibody
specific to tetrodotoxin has been developed
by USAMRIID and was shown to be effective for reducing
lethality in murine tests.

16. http://en.wikipedia.org/wiki/Tetrodotoxin
 Poisoning from tetrodotoxin is of particular public
health concern in Japan, where pufferfish "fugu" is a
traditional delicacy. It is prepared and sold in special
restaurants where trained and
licensed chefs carefully remove the viscera to
reduce the danger of poisoning. There is potential for
misidentification and mislabelling, particularly of
prepared, frozen fish products.

17. END