Thursday, September 30, 2021

Tetrodotoxin

 

Tetrodotoxin (TTX) is a powerful neurotoxin. Its name comes from Tetraodontiformes, which includes pufferfish, porcupines, sunfish, and triggerfish; some of these species carry toxins. Although tetrodotoxin has been found in these fish and several other animals. It is actually produced by certain infectious or symbiotic bacteria, such as Pseudoalteromonas, Pseudomonas and Vibrio, and other species found in animals. 

The highly contaminated parts of fish (liver, skin, reproductive organs) must be professionally removed before consumption. Tetrodotoxin is thermally stable, so it cannot be decomposed after being cooked.



Effects:

It looks like a colorless crystalline solid, which darkens when heated above 220°C (428°F). Tetrodotoxin is a sodium channel blocker. It inhibits the triggering of action potentials in neurons by combining with voltage-gated sodium channels in nerve cell membranes and preventing sodium ions (responsible for the rising phase of action potentials) from entering neurons. 

This prevents the nervous system from transmitting information and prevents muscles from contracting due to nerve stimulation. Causes loss of sensation, paralysis, respiratory failure, and death. The estimated average lethal dose of tetrodotoxin is 0.33 mg per kilogram of body weight. There is no known antidote for toxins.


TTX blocks voltage-gated sodium channels and causes paralysis. It can also be used as a potential analgesic. Some researchers are trying to use the analgesic activity of TTX to treat different types of pain, such as severe cancer pain.
 
Its mechanism of action, Selective blocking of sodium channels, was established in 1964 and finally demonstrated by Toshio Narahashi and John W. Moore at Duke University, using sucrose gap tension clamp technology.

Toxicity:

TTX is extremely toxic. The material safety data sheet of TTX gives a mouse oral median lethal dose of 334 µg/kg. As a comparison, the oral lethal dose ​​of potassium cyanide in mice is 8.5 mg/kg, which shows that the oral toxicity of TTX itself is greater than that of cyanide.

TTX is more dangerous when injected; the amount required to achieve a lethal dose by injection is only 8 micrograms per kilogram of mice.

Treatment:

No antidote is known. The main pillars of treatment are respiratory support and supportive treatment until the tetrodotoxin is excreted in the urine. If the patient sees a doctor within 60 minutes of ingestion, activated charcoal and/or gastric lavage can be performed.

Tetrodotoxin is a storyline tool for the suspended animation of characters, such as the movie Captain America: The Winter Soldier (2014) and War (2019).

Reference:

1) https://en.wikipedia.org/wiki/Tetrodotoxin#:~:text=Tetrodotoxin%20is%20a%20sodium%20channel,action%20potential)%20into%20the%20neuron.

2) https://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750019.html

3) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626696/

4) https://www.sciencedirect.com/topics/neuroscience/tetrodotoxin

5) https://www.youtube.com/watch?v=F8FIPRD9jvg



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