• 한국동물학회지
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• 제28권4호
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• pp.227-236
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• 1985

LDH 동위효소의 4차구조 형성기작을 규명하기 위한 일환으로 웅성 흰쥐 복강내에 여러 가지 농도의 tetrodotoxin을 수차 주사한 후, 전기영동 및 densitometry에 의해 여러 조직내의 5가지 동위효소의 상대적 분포의 변화를 조사하였다. 뇌조직에서는 $H_4$ 동위효소가 현저히 증가하였고, 골격근조직에서 $M_4$ 동위 효소는 약간 증가한 반면 $M_3H$ 및 $M_2H_2$ 동위효소들은 감소되었으며, 심장조직에서는 M/H 비가 급격히 감소되었으며, 간조직에서는 소량의 $H_4$ 동위효소 형성이 나타났다. 이러한 결과들은 Donnan막 평형의 변화가 LDH 동위효소 분포의 변화를 초래할 수 있음을 시사한다. Tetrodotoxin에 노출된 흰쥐의 여러 조직내에서 $M_3H$ 동위효소 형성이 감소되는 사실로 미루어 고유한 세포질내 환경이 변화되면 3M+H 조합은 쉽게 이우러지지 않는 것으로 사료된다. 원형질 막의 어떤 sodium channel은 tetrodotoxin에 민감하지 않다는 사실이 재확인 되었다.

• 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.

• 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.

• 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.

• 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.

• The Korean Journal of Physiology
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• 제20권2호
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• pp.192-198
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• 1986

dopamine이 십이지장구를 포함한 소장의 운동성에 미치는 영향, cholecystokinin이 dopamine의 작용에 미치는 영향 그리고 이들 작용의 신경성 기전을 알아보고자 다음과 같은 실험을 실시하였다. ether로 마취한 토끼 54마리에서 십이지장구, 십이지장, 공장 그리고 회장을 적출하고 절편(길이 1cm)을 만들어 Krebs-Ringr 용액이 채워진 기록 용기에 넣고 자발적인 등장성 수축을 기록하였다. Krebs-Ringr 용액에는 5% $Co_2$를 함유하는 $O_2$를 계속 공급하였으며, 용액의 온도가 $37^{\circ}C$를 유지하도록 하였다. 자발적 수축이 시작하고 20분이 경과한 다음 dopamine($10^{-4}M$), CCK-8($10^{-8}M$), dopamine($10^{^6}M$)등을 투여하면서 수축성을 관찰하여 다음과 같은 결과를 얻었다. 1) dopamine은 소장의 모든 부위에서 자발적 수축성을 억제하였으며, 이러한 dopamine의 작용은 회장을 제외한 다른 부위에서 tetrodotoxin에 의하여 유의하게 감소하였다. 2) domperidone은 소장의 모든 부위에서 dopamine의 억제작용에 길항적으로 작용하였으며, tetrodotoxin을 전처치하면 회장을 제외한 다른 부위에서 domperidone의 길항작용은 완전히 소실되었다. 3) CCK-8는 소장의 모든 부위에서 dopamine의 작용을 감소시켰으며, tetrodotoxin을 전처치하면 CCK-8의 작용은 유의하게 감소되었다. 이상의 결과로 미루어 보아 dopamine은 십이지장구를 포함한 모든 소장의 수축성을 억제하며, CCK-8는 dopamine의 억제 작용을 감소시키는데, 이러한 작용들은 장관내 신경계를 거쳐서 간접적으로 일어나는 것으로 생각된다.

• 대한약리학회지
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• 제29권2호
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• pp.183-188
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• 1993

시상하부 조각에서 카테콜아민의 분비에 대한 포도당의 영향을 관찰하였다. 카테콜아민의 기초분비는 포도당의 농도$(5{\sim}30mM)$에 반비례하였다. Tetrodotoxin $(10\;{\mu}M)$의 존재하에서 카테콜아민의 기초분비에 대한 포도당의 억제 작용은 대부분 유지되었으나, 도파민에 대한 30 mM 포도당의 억제 작용은 거의 봉쇄되었다. Tetrodotoxin $(10\;{\mu}M)$과 desipramine $(3\;{\mu}M)$의 존재하에서는 카테콜아민의 기초분비에 대한 포도당의 영향이 없었다. 이상의 결과는 포도당이 transsynaptic action 뿐 아니라 카테콜아민 신경세포 말단에 대한 직접 작용을 통하여 카테콜아민의 분비를 조절할 것임을 시사한다. 카테콜아민의 분비에 대한 포도당의 조절작용은 당뇨상태에서의 시상하부 카테콜아민 대사의 변화를 적어도 부분적으로는 설명할 수 있으리라 사료된다.

• 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.

• 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.