Monday, December 2, 2024

Deliciously Deadly- Fugu

Fugu also known as pufferfish is an eastern delicacy. While portions of puffer fish can be consumed when handled by those with a fugu license, there are deadly consequences for any incorrect cuts or handling of the fish causing the leaching of the neurotoxin tetrodotoxin.

So how does tetrodotoxin (TTX) work? 

TTX competitively inhibits voltage-gated sodium channels which stops the production and dispersion of action potentials. This is a huge issue for many cells in the body, most importantly neurons and muscle cells. TTX is dose dependent meaning there is some leeway in how much a person can consume but really only one to two mg of TTX can be lethal to adults.


Symptoms- Initially just tingling and numbness around the mouth, salivation, nausea, vomiting and lethargy. Due to the total loss of function in sodium channels some more severe effects are done to the lungs. Paralysis of the lungs and diaphragm inhibit the creation of the pressure gradient which essentially stops the patient from breathing leading to death. On the same token when the heart is subjected to TTX the patient presents with bradycardia and hypotension yet total paralysis of the heart was not mentioned. The blood brain barrier also offers some protection because patients have been completely conscious while paralyzed in mild cases. 


Treatment revolves around treating the patients paralysis of the lungs. Quick ventilation intravenous fluids and vasopressors are used to eliminate TTX and some cases use cholinesterase inhibitors. 


Current TTX Research

Interestingly enough TTX has been seen as a possible analgesic (pain relief medication that does not cause loss of consciousness in patients) for cancer related pain. A meta analysis of varying studies using TTX found that it could reduce cancer-related pain without producing serious adverse events in patients.

A dose of just 30 micro grams twice a day significantly increased the

number of patients who achieved an improvement in pain intensity versus the placebo group. Additionally, 47% maintained persistent relief of cancer pain that was present during successive treatment cycles without any evidence of tolerance.


Nearly all adverse effects of TTX at this dosage were considered mild or moderate, with sensory alterations and gastrointestinal issues being the most common. No deaths were reported in treatment groups. 


As previously mentioned, the heart did not fully stop as a symptom which is due to Nav1.5 isoform, which from what I gather is a specific channel, being TTX-resistant. Nav1.5 maintains the heart's upstroke of action potential in the heart as they worded it which means no patient cardiac failure. 

This research, while intimidating given it is a neurotoxin, is a tremendous step forward because cancer pains are so complex and really debilitating for patients if it works for even a few people then its worth pursuing personally.




References

Huerta, M., De La Nava, J., Artacho-Cordón, A., & Nieto, F. (2023, May 21). Efficacy and security of tetrodotoxin in the treatment of cancer-related pain: Systematic review and meta-analysis. MDPI. https://www.mdpi.com/1660-3397/21/5/316

Kheifets, J., Rozhavsky, B., Girsh Solomonovich, Z., Marianna, R., & Soroksky, A. (2012). Severe tetrodotoxin poisoning after consumption of lagocephalus sceleratus (pufferfish, fugu) fished in Mediterranean Sea, treated with cholinesterase inhibitor. U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010039/

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