Tetrodotoxin
Tetrodotoxin (TTX) is a very effective poison, inhibitingly acting on voltage-gated sodium channels, thereby preventing the formation of an action potential on the membranes of neurons . It is a thermostable substance that is soluble in water.[1]
Although this neurotoxin is undoubtedly synthesized by bacteria, it has been isolated from a number of animals, including the Japanese Fugu fish . is responsible for the presence of the toxin in the organs (especially the liver, gonads and skin) of Fugu Specifically, the bacterium Vibrio alginolyticus fish .
Mechanism of action[edit | edit source]
Tetrodotoxin binds with high potency already at nanomolar concentrations (5–15 nM) especially to sodium channels in nervous tissue and skeletal muscle , while the myocardium is more resistant and sodium channel blocking only occurs at a concentration of ~10 −5 M. The toxin binds to α-subunit, which consists of four repeating domains (I–IV). Each domain consists of another six segments (S1–S6), in this case the toxin binds to amino acids in the so-called P-loop between segments S5–S6 of domain I, which protrudes above the outer mouth of the channel. These P-loops are present in all four domains, forming the outer entrance to the ion channel.[2][3]
Toxicity[edit | edit source]
TTX poisoning can occur through ingestion, inhalation, injection, or even through skin abrasions.[4] The LD 50 in mice is reported to be 334 μg/kg when administered per os, while the lethal dose is only 8 μg/kg when injected.[5] .TTX poisoning occurs in humans especially after eating improperly prepared Fugu fish, which is a sought-after culinary specialty. The course of poisoning depends on the ingested dose. During the first 30 minutes of ingestion, poisoning is manifested by gradual numbness, first of the lips and tongue, later of the limbs, but if the dose is fatal, the symptoms appear earlier. There is weakness, loss of coordination, nausea, lethargy and gradually paralysis, with higher doses cardiac arrhythmia may occur. The affected person does not always have to fall into a coma - he can be completely conscious. The cause of death is respiratory muscle failure , depending on the ingested dose, after 8 hours.
Treatment[edit | edit source]
Since there is no antidote , the treatment is symptomatic . After ingestion, the amount of absorbed TTX can be reduced in the emergency room by gastric lavage and administration of activated charcoal. If the person survives acute poisoning, they will fully recover within a few days without any consequences.[6] During experiments on mice, it was possible to prepare effective specific monoclonal antibodies against TTX, but this method has not yet been tested in humans.[7]
Usage[edit | edit source]
TTX has been tested as an analgesic for cancer patients, with a demonstrable positive effect on pain relief. A clinical trial has also been established to demonstrate that TTX alleviates withdrawal symptoms in heroin withdrawal syndrome
Links[edit | edit source]
Resources[edit | edit source]
- ↑ (Pt 3), 647–657. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-7793.1998.647bp.x
- ↑ Marban, E., Yamagishi, T., & Tomaselli, G. F. (1998). Structure and function of voltage-gated sodium channels. The Journal of Physiology, 508(Pt 3), 647–657. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-7793.1998.647bp.x
- ↑ Lu, Jian, Zheng, Jianzhou, Xu, Qinggang, Chen, Keping, & Zhang, Chiyu. (2011). Adaptive evolution of the vertebrate skeletal muscle sodium channel. Genetics and Molecular Biology, 34(2), 323-328. https://dx.doi.org/10.1590/S1415-47572011000200026
- ↑ Patockaa J, Stredab L (April 23, 2002). Price R, ed. "Brief Review of Natural Nonprotein Neurotoxins". ASA Newsletter. Applied Science and Analysis inc. 02–2 (89): 16–23. ISSN 1057-9419. Retrieved 26 May 2012.
- ↑ Gilman AG, Goodman LS, Gilman AZ (1980). Goodman & Gilman's The pharmacological Basis of Therapeutics. New York: McGraw-Hill. p. 310. ISBN 0-07-146891-9.
- ↑ Benzer T. "Tetrodotoxin Toxicity". Medscape. Retrieved 23 August 2015.
- ↑ Rivera VR, Poli MA, Bignami GS (Sep 1995). "Prophylaxis and treatment with a monoclonal antibody of tetrodotoxin poisoning in mice". Toxicon. 33 (9): 1231–7.
