Pufferfish poisoning may soon be treatable in China! What are the symptoms? How long is the incubation period?
On May 28, it was learned from Nankai University that a research team led by the university's State Key Laboratory of Medicinal Chemical Biology successfully “decoded” the two target genes of tetrodotoxin using monkey haploid neural stem cells, and through gene knockout experiments, enabled neural cells to acquire resistance to tetrodotoxin. This research will make pufferfish poisoning patients “treatable”. The related results were published online in the latest issue of Development, an academic journal in the field of stem cells and neural development.
Pufferfish is delicious, yet tetrodotoxin is extremely toxic, often causing instant death in those who accidentally eat it, and its targets of action and toxicological mechanism have so far remained unknown. Existing research suggests that tetrodotoxin is a type of neurotoxin, and its toxicology may involve blocking sodium and potassium ion channels within nerve cells, thereby causing toxic effects. So, can monkey haploid neural stem cells be used to screen for the “action points” of tetrodotoxin on the nervous system?
The team led by [the researcher] started from the reverse direction, and by leveraging the emerging haploid cell tool culture technology of recent years, through adopting a naive pluripotency culture system, enabled monkey haploid embryonic stem cells to have better haploid maintenance and cell survival ability during in vitro differentiation, and for the first time worldwide obtained monkey haploid neural stem cells with in vitro proliferation ability. In the experiment, the researchers then subjected the obtained monkey haploid neural stem cells to high-throughput genome-wide random mutagenesis, and subjected the mutated cell lines to tetrodotoxin killing experiments. Ultimately, through bioinformatics analysis and gene editing experiments, it was confirmed that the key target genes of tetrodotoxin are B4GALT6 and SCN5A. From a genetic perspective, since the specific functional genes that directly carry out the toxic function have been found, in theory, as long as these target genes are knocked out, neural cells can acquire resistance to tetrodotoxin.
According to the introduction, since the gene similarity between monkeys and other primates and humans is very high. For humans, finding the target genes means that detoxification can be achieved by taking gene inhibitors. This also means that in the near future, people poisoned by pufferfish toxin will no longer be beyond saving.
Introduction to Pufferfish
Pufferfish is the collective name for fish of the family Tetraodontidae in the class Osteichthyes, commonly known as pufferfish. (Note: the term “pufferfish” is incorrect, but is widely used; pufferfish can also refer to a type of freshwater mammal.) Since ancient times, the pufferfish eaten in China have all lived in rivers, and got the name river "puffer" because they make a squeaking sound similar to a pig's squeal when caught and brought out of water. They are also called “bubble fish”, “belly-blowing fish”, “pufferfish”, “balloon fish” (Jiangsu, Zhejiang), “guai fish, chicken bubble” (Guangdong), “chicken hug” (Guangdong), “turtle fish” (Guangxi), “street fish” (read in Minnan dialect) (Fujian), “wax head” (Hebei), “ting ba fish” and other names. In ancient times it was called “lungfish”.
The toxin of pufferfish is mainly distributed in the ovaries and liver, followed by the kidneys, blood, eyes, gills and skin; while the testes and muscles are non-toxic. If the fish has been dead for a relatively long time, the visceral toxins dissolve into the body fluids and can gradually seep into the muscles. The amount of toxin often varies with the season. Every year from February to May is the ovarian development period, when toxicity is relatively strong; after spawning from June to July, the ovaries degenerate and toxicity weakens. The liver also has the strongest toxicity during the spring spawning period. Therefore, whenever eating fresh pufferfish in late spring and early summer, special caution should be taken; live fresh fish must be selected and the internal organs strictly removed to avoid poisoning.
Symptoms and Incubation Period of Pufferfish Poisoning
The incubation period is 0.5 to 3 hours. Gastrointestinal symptoms appear first, such as nausea, vomiting, diarrhea, and abdominal pain, followed by sensory and motor dysfunction, numbness of the lips, tip of the tongue, extremities and the whole body, and limb weakness. Ptosis of the eyelids, ataxia, hoarseness, and in severe cases difficulty breathing, arrhythmia and conduction block, and coma; finally respiratory and circulatory failure appear. Tetrodotoxin is detoxified and excreted relatively quickly in the human body, and those who do not die within 8 hours can mostly recover.