• 생명과학회지
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• 제9권6호
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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.

• 생명과학회지
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• 제10권2호
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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.

• The Korean Journal of Physiology
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• 제10권1호
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• pp.41-48
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• 1976

Tetrodotoxin (TTX) is the purified active principle responsible for tetrodon (Puffer-fish) poisoning which has long been known in the Orient. The pharmacological actions of TTX have been rather extensively investigated. Two of the most prominent effects of intravenousely administered TTX are severe hypotension and respiratory paralysis resulting from its depressant actions on tissues. This depressant actions of TTX in turn result from the selective inhibition of sodium-carrying mechanism which is essential to generation of the action potential. TTX differs from local anesthetics in that it does not affect potassium conductance. Although the mechanism of the hypotensive action of TTX remains a subject of controversy, most investigator agree that TTX-induced hypotension is caused by alteration in the blood vessels rather than the heart. Not only the study on the effects of TTX on cardiac function is meager but the results of reported works are often contradictory. The present study was undertaken to investigate the effect of TTX on the electrocardiogram of the rabbit and to compare them with well known electrocardiographical characteristics found in digitalis and quinidine intoxicated animals. The results obtained from the present study are summarized as follows. 1. No changes were found in P-R interval and QRS duration after i.v. administration of $1.0\;{\mu}g/kg\;to\;1.5\;{\mu}g/kg$ TTX to the animals. It is obvious that there were no conduction disturbance between atria and ventricles as well as in the ventricular tissue. 2. In $1.0\;{\mu}g/kg$ TTX group, S-T interval and T-P segment were not changed whereas marked changes were observed in $1.5\;{\mu}g/kg$ TTX group. 3. The first and second degree A-V blocks appeared in the $2.0\;{\mu}g/kg$ TTX group. 4. TTX differs from digitalis and quinidine in that it does not cause S-T interval depression and T-wave inversion. In contrast with digitalis, TTX caused Q-T interval prolongation.

• 생명과학회지
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• 제10권2호
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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.

• 한국수산과학회지
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• 제29권6호
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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 Acupuncture Research
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• 제32권1호
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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.

• 대한약침학회지
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• 제3권2호
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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.

• 한국어병학회지
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• 제22권1호
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• pp.67-73
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• 2009

양식산 복어에서는 tetrodotoxin(TTX)가 존재하지 않는다고 일반적으로 생각되고 있다. 본 연구에서는 실제로 양식산 황복(Takifugu obscurus)에는 TTX가 존재하지 않는지 확인하기 위해 생쥐를 이용한 bioassay로 여러 장기를 동시에 분석하였다. 자연산에서는 동물이 치사하는 수준의 독력을 함유한 시료가 있었으며 정소>간장>장>근육>피부의 순으로 독력이 확인되었다.양식산 시료에서는 TTX의 미량존재로 추정되는 졸림, 행동둔화, 후지마비 등의 증상이 나타났지만 치사동물은 발견되지 않았다. 이 결과는 양식 산 황복에서 TTX가 매우 낮은 농도로 존재할가능성을 제시하지만 기기분석법을 이용한 정확한 정량이 필요하다고 판단된다.

• The Korean Journal of Physiology
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• 제11권2호
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• pp.23-31
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• 1977

It is Proposed in the Present study to investigate the effects of TTX intravenously or intrahypothalamically administered on the arterial blood pressure and respiration and also to explorc effect of intrahypothalamically administered TTX on the pressor responses to electrical stimulation in the hypothalamus. The results obtained are as follows; 1) The pressor responses to electrical stimulation in the hypothalamus were markedly reduced after administration of TTX. In the $0.01\;{\mu}g/kg$ of TTX administered group, the pressor responses were almost abolished in 6 minutes and there was no tendency toward recovery throughout the experiment. 2) In $0.01\;{\mu}g/kg$ of TTX administered group, the mean arterial blood pressure and heart rate-were gradually reduced while there was a transient increase in respiratory rate followed by slow recovery thereafter. On the other hand no changes in arterial blood pressure, heart rate an4 respiration were observed in $0.005\;{\mu}g/kg$ TTX administered group. 3) Following intravenous administration of $1\;{\mu}g/kg$ TTX, the arterial blood pressure and heart rate were slowly reduced by 60 minutes while no marked changes were found in respiration. From the results of present study it is strongly suggested that TTX exerts its depressant effect not only on peripheral nerves but also on central nervous system.

• The Korean Journal of Physiology
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• 제29권1호
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• pp.103-111
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• 1995

Intracellular recordings were obtained from Purkinje cells in rat cerebellar slices maintained in vitro. Adding tetrodotoxin to the superfusion solution produced a typical pattern of repetitive burst firing consisting of a cluster of action potentials followed by a long hyperpolarization. TTX-induced oscillatory activity was not due to modulation of membrane potential although underlying mechanisms for maintenance of oscillatory activity were influenced by membrane voltage. The mechanism of TTX-induced oscillation was not related to the presence or amplitude of $I_h$ and could still induce the oscillatory activity after blockade of $I_h$ by cesium. The result from an experiment in which QX-314 was injected intracellularly strongly suggested that TTX-induced oscillatory firing activity was due to blockade of post-synaptic $Na^{+}$ currents intrinsic to PCs.