• The Korean Journal of Zoology
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• v.28 no.4
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• pp.227-236
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• 1985

In an attempt to make a scrutiny into a mechanism for the formation of quaternary structure of LDH isozymes, male mice were intraperitoneally exposed to a wide range of tetrodotoxin concentration and the changes in relative percentage of the five isozymes were monitored by electrophoresis and subsequent densitometry. The observations that a conspicuous increase of the $H_4$ isozyme was demonstrated in nearly all brain tissues, that the $M_4$ isozyme of skeletal muscle tissue was slightly increased while the $M_3H$ and $M_2H_2$ isozymes were decreased, that the M/H ratio was strikingly reduced in heart tissue and that assembly of $H_4$ isozyme was revealed in liver tissue although its rate was extremely low suggest that new intracellular ionic environment established by compulsory change in Donnan equilibrium could alter the LDH isozyme distribution. The reduction of assembly of $M_3H$ isozyme found in mouse tissues exposed to tetrodotoxin also seems to suggest that the subunit combination of 3M+H is very unfavorable in an intracellular environment deviated from its accustomed one. It was reaffirmed that there might occur TTX-insensitive sodium channels in plasma membrane.

• Journal of Acupuncture Research
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• v.32 no.1
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• pp.97-107
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• 2015

Objectives : The purpose of this study is to explore the antitumor mechanism and effects of tetrodotoxin through a literature review of experimental and clinical studies. Methods : Medical databases, including The Cochrane Library, Pubmed, NDSL, RISS4u and National Assembly Library, were searched for relevant articles published from January 1, 2000 to October 31, 2014 using the keywords 'tetrodotoxin', 'cancer' and 'tumor'. The results were classified into experimental studies(in vitro and in vivo) and clinical studies. Analysis of the results was conducted on several research areas including the mechanism, antitumor effect and adverse effects of tetrodotoxin(TTX). Results : A total of 34 experimental studies(32 in vitro and 2 in vivo) and 3 clinical studies were found in the search. Most of the experimental studies suggested blocking of voltage-gated sodium channels in metastasis of tumor cells as the main antitumor mechanism of TTX. The most common type of cancers mentioned in the experimental studies were prostate and breast cancer. All of the clinical studies were on the application of TTX on moderate to severe cancer-related pain. No adverse effects of TTX were reported in in vivo studies but mild to moderate adverse events were reported in clinical studies. Conclusions : The results show that tetrodotoxin, which is the main component of Tetraodontidae(commonly known as pufferfish) poison, could be clinically used for antitumor therapy. However, further studies should be conducted on its safety.

• Journal of Life Science
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• v.9 no.6
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• pp.653-658
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• 1999

A novel marine microorganism, Vibrio sp. YE-101, was isolated from pufferfish and investigated for its ability to synthesize tetrodotoxin (TTX). Various strains isolated from the intestine of pufferfish were grown on TCBS agar plate, and then cultured on Ocean Research Institute (ORI) medium supplemented with 3% NaCl at 23$^{\circ}C$ for 3days. The cells were harvested, disrupted, fractionated by Bio-Gel P-2 column chromatography and then TTX-producing strain, Vibrio sp. YE-101, was identified using mouse bioassay. The isolated TTX from Vibrio sp. YE-101 was also analyzed and identified by HPLC and gas chromatography-mass spectrometer (GC-MS). The mass fragmentation of trimethylsilyl derivatives of C9-base of TTX from Vibrio sp. YE-101 was interpreted and the pattern of fragmentation was same with that of authentic standard. The purfied TTX was also positive to the mouse bioassay, which clearly represents that Vibrio sp. YE-101 can synthesize TTX.

• Journal of Life Science
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• v.10 no.2
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• pp.115-124
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• 2000

The present study was undertaken to separate the available components effectively, such as tetrodotoxin(TTX), docosahexaenoic acid(DHA, C22:6,ω-3) and eicosapentaenoic acid (EPA, C20:5,ω -3) from pufferfish liver waste, which are known to have high values as bioactive materials. By using ultrafiltration, it was possible to separate high contents of 68mg TTX from pufferfish liver waste. In contrast, by activated charcoal column, it was to obtain about 54mg TTX. The recovering ratios were 65.3% and 45.0% in the two different methods of ultrafiltration and activated charcoal column, respectively. From the results of HPLC and gas chromatography-mass spectrometry(GC-MS), the obtained toxins were identified to be TTX and its derivatives. In addition, it was also possible to obtain 72.3g DHA and 11.4g EPA from 1kg of pufferfish liver by high performance liquid chromatography (HPLC). These amounts of DHA and EPA were also 17.70% and 1.04% in the total lipid of pufferfish liver oil from analysis of gas chromatography(GC), respectively.

• Journal of Life Science
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• v.10 no.2
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• pp.196-201
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• 2000

The production of tetrodotoxin (TTX) using Vibrio sp. YE-101, a novel marine microorganism isolated from the intestine of pufferfish, was investigated. Culture condition was optimized for the enhanced production of TTX using response surface methodology. The experimental sets of environmental conditions including pH, temperature and NaCl concentration were designed using central composite experimental design. The optimal conditions of pH, temperature and NaCl concentration were determined to be 8.1, 29.2℃, and 2.6% (w/v) respectively. The relative growth extent could be enhanced up to 80%, and final mouse unit (MU) value of TTX was also enhanced up to 87% by response surface optimization.

• Journal of Pharmacopuncture
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• v.3 no.2
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• pp.1-25
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• 2000

We were trying to study the validity of Puffer fish's poison(Tetrodotoxin- TTX) to make a traditional Korean Medical treatment. The following conclusions were made after literary studies. 1. The first record of the puffer fish dates back 2000 years ago in the Chinese text Book of Mountain and Sea and other texts from the similar period. 2. Puffer fish's poison IS known as tetrodotoxin which is an amino perhydroquinazoline compound. It has a chemical formula of $C_{11}H_{17}N_3O_8$ in the hemiacetal structure and has the molecular weight of 319. 3. Tetrodotoxin (TTX) plays a role as potent neurotransmitter blocker by blocking the $Na^+$ -gate channel which hinders the influx of $Na^+$ ion into the cell. 4. Symptoms of the puffer fish poisoning ranges from blunted sense in the lips and tongue, occasional vomiting in the first degree to sudden descending of the blood pressure, apnea, and other critical conditions in the fourth degree. Intoxication of the puffer fish poison progresses at a rapid pace as death may occur after an hour and half up to eight hours in maximum. Typical death occurs after four to six hours. 5. Ways to treat the puffer fish poisoning include gastric irrigation, induce vomiting, purgation, intravenous fluid injection, and correcting electrolytic imbalance and acidosis. In cases of dyspnea, apply oxygen inhalation and conduct artificial respiration. 6. Tetrodotoxin (TTX) may be applied in treating brain disorders, ocular pain, excess pain in the large intestine and ileum, and relieving tension of the skeletal museles, neuralgia, rheumatism, arthritis, and etc. 7. In terms of Oriental medicine, the puffer fish poison has characteristics of sweet, warm, and poisonous. It's known efficacies are to tonify weakness, dispel damp, benefit the lower back, relieve hemorrhoid, kills parasites, remove edema, and so forth. And the puffer fish eggs processed with ginger are said to be effective against tuberculosis and lung cancer, thus, it's validity must be investigated and further research should be followed.

• The Korean Journal of Physiology
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• v.20 no.2
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• pp.192-198
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• 1986

The present study was undertaken to see an interaction of dopamine and cholecystokinin on spontaneous contractility of the small intestine including the duodenal bulb. A possible neural mechanism of the interaction was alto examined. The spontaneous isometric contractility of a segment of the duodenal bulb, duodenum, jejunum and ileum obtained from the rabbit anesthetized with ether was recorded in a chamber filled with Krebs-Ringer's solution. The solution was constantly kept at $37^{\circ}C$ and aerated with $O_2$ containing 5% $CO_2$. After 20 min from beginning of the contraction, dopamine $(10^{-4}M)$, CCK-8($10^{-8}M$), domperidone($10^{-5}M$) and tetrodotoxin ($10^{-6}M$) were administered into the chamber The following results were obtained by analyzing changes in the contractility of the intestinal segments. 1) Dopamine inhibited the spontaneous contractility of the duodenal bulb, duodenum, jejunum and ileum. The inhibitory action of dopamine on all parts of the small intestine except the ileum was reduced by tetrodotoxin. 2) Domperidone knwon to be a specific peripheral dopamine receptor antagonist blocked the inhibitory action of dopamine on all parts of the small intestine. The antagonistic action of domperidone on all parts of the small intestine except the ileum was completely abolished by tetrodotoxin. 3) CCK-8 reduced the inhibitory action of dopamine on all parts of the small intestine. The effect of CCK-8 on the dopamine action was diminished by tetrodotoxin. These results suggest that dopamine inhibits the spontaneous contractility of the small intestine including the duodenal bulb and CCK-8 reduces the inhibitory action of dopamine through the enteric nervous system.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.183-188
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• 1993

Effects of glucose on the catecholamine release from the hypothalamic fragments in vitro were studied. Basal release of catecholamines was inversely related to the concentrations $(5{\sim}30\;mM)$ of glucose in the incubation medium. Glucose did not affect the 30 mM $K{^+}-stimulated$ release of catecholamine. In the presence of tetrodotoxin $(10\;{\mu}M)$, the inhibitory effect of glucose on the basal release of catecholamines was largely persisted, but the inhibitory effect of 30 mM glucose on dopamine release was largerly blocked. In the presence of both tetrodotoxin $(10\;{\mu}M)$ and desipramine $(3\;{\mu}M)$, glucose failed to affect the basal catecholamine release. The results suggest that glucose modulates the catecholamine release through a direct action on the catecholaminergic nerve terminals, as well as through a trans-synaptical action. The glucose-modulation of the catecholamine release may explain, at least in part, the diabetes-induced changes in the hypothalamic catecholamine metabolism.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.29 no.6
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• pp.856-861
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• 1996

The occurrence of TTX in ciliated protozoa was investigated in order to clarify tetrodotoxin (TTX) accumulation mechanisms in marine organisms. Tissue culture bioassay, HPLC, and GC-MS analyses confirmed the occurrence of TTX in Euplotes mutabilis and also in bacteria isolated from the culture medium. Fluorescently labeled bacteria (FLB) were prepared with those bacteria, and predation by E. mutabilis was observed. The results indicated that TTX in bacteria can be transferred to higher trophic levels through the food chain.

• Journal of fish pathology
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• v.22 no.1
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• pp.67-73
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• 2009

It was examined whether the common belief that "cultured puffer fishes do not contain tetrodotoxin (TTX)", the major lethal substance that accidently causes death in consumers of those fishes, is true in river puffer fish Takifugu obscurus. In mouse bioassay, lethal levels of toxins were detected in the ranks: gonad>liver>intestine>muscle>skin in wild puffer fish. In contrast, no mortality occurred in the mouse bioassay on cultured fish. However, there were sleepiness, sluggish behavior, and hind limb paralysis with the tissue extracts of cultured fish suggesting the presence of TTX or other similarly acting toxins. An attempt to confirm the presence of TTX in cultured fish with high performance liquid chromatography (HPLC) was not very successful. The results suggest possible existence of TTX toxins or similarly acting toxins.