• Restorative Dentistry and Endodontics
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• 제25권3호
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• pp.407-420
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• 2000

삼차신경절의 뉴런이 구강악안면영역에서의 촉각, 입각, 온도각 및 통각 등 다양한 감각을 중추신경계로 전달하는 역할을 하는 것은 주지의 사실이다. 이러한 신경전달에 있어서 이온통로는 감각정보를 전달하는데 핵심적인 역할을 수행하며 특히 소디움 통로는 활동전위의 발생에 중요하다. 소디움 통로는 tetrodotoxin-sensitive(TTX-s) 및 tetrodotoxin-resistant(TTX-r) 통로로 나누어지는 데 이 중 TTX-r 통로에 발생되는 tetrodotoxin-resistant sodium current(TTX-r $I_{Na}$)는 capsaicin에 민감한 일차구심신경세포에서 유해자극에 의해 통각신호를 발생시키고 전달하는데 중요하다. 또한 칼슘 통로는 시냅스 전도에 있어서 필수적인 역할을 수행하고 있다 한편 치과영역에서 치수의 진정 목적으로 eugenol이 흔히 사용되고 있다. 그러나 eugenol의 그 작용 기전에 대해서 현재까지 이온 통로에 대한 상세한 결과가 없는 실정이며 최근의 보고에 의하면 eugenol이 capsaicin 수용기를 통하여 감각신경에 대한 억제작용을 나타낸다고 한다. 따라서 본 실험은 eugenol과 capsaicin이 흰쥐의 삼차신경절의 TTX-r $I_{Na}$와 칼슘통로에 어떠한 영향을 미치는지를 알아보고 eugenol이 capsaicin 수용기를 통하여 작용하는지를 검증하고자 시행되었다. 삼차신경절 뉴런은 100~150g의 흰쥐의 삼차신경절로부터 외과적으로 절제하여 통법의 화학적 및 기계적 처리를 통해 단일세포로 분리하였고 이를 whole-cell patch clamp 방법을 이용하여 시행한 바 다음과 같은 결론을 얻었다. 1. 1mM의 dugenol은 흰쥐 삼차신경절 뉴런의 TTX-r $I_{Na}$와 HVA $I_{Ca}$를 억제하였다. 2. $1{\mu}m$의 capsaicin은 흰쥐 삼차신경절 뉴런의 TTX-r $I_{Na}$와 HVA $I_{Ca}$를 억제하였다. 3. Capsazepine은 capsaicin의 HVA $I_{Ca}$에 대한 억제작용을 차단하였다. 4. Capsazepine은 capsaicin의 HVA $I_{Ca}$에 대한 억제작용을 차단하지 못하였다. 결론적으로 eugenol과 capsaicin은 tetrodotoxin-resistant sodium current(TTX-r $I_{Na}$)와 high voltage-activated calcium current(HVA $I_{Ca}$)를 모두 억제하는 것으로 나타났으며, 이러한 작용이 통각의 발생과 시냅스 전달과정을 차단하여 치수 진정 목적으로 많이 사용하는 eugenol의 작용기전으로 판단된다. 한편 capsaicin의 길항제인 capsazepine을 전처치하였을 때에도 eugenol의 HVA $I_{Ca}$에 대한 억제효과는 변화가 없었다. 이와같은 결과로 보아 HVA $I_{Ca}$에 관한 한 eugenol은 capsaicin 수용기를 통하여 나타나지 않는 것으로 사료된다.

• Fisheries and Aquatic Sciences
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• 제24권11호
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• pp.360-369
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• 2021

Paralytic shellfish toxins (PSTs) and tetrodotoxin (TTX) are neurotoxins that display pharmacological activity that is similar to that of specific sodium channel blockers; they are the principle toxins involved in shellfish and puffer fish poisoning. In Korea, puffer fish is a very popular seafood, and several cases of accidental poisoning by TTX have been reported. Therefore, it is necessary to determine whether puffer fish poisoning incidents are caused by PSTs or by TTX. In this study, we used mouse bioassay (MBA) and liquid chromatograph-tandem mass spectrometry (LC-MS/MS) to determine the presence of PSTs and TTX in puffer fish from an area near Mireuk-do, Tong-Yeong on the southern coast of Korea from January through March, 2014. The toxicity of PSTs and TTX extracts prepared from three organs of each specimen was analyzed by MBA. Most of the extracts killed mice with typical signs of TTX and PSTs. The LC-MS/MS analysis of seven specimens of Takifugu pardalis and Takifugu niphobles, each divided into muscles, intestines, and liver, were examined for TTX. In T. pardalis, the TTX levels were within the range of 1.3-1.6 ㎍/g in the muscles, 18.8-49.8 ㎍/g in the intestines, and 23.3-96.8 ㎍/g in the liver. In T. niphobles, the TTX levels were within the range of 2.0-4.5 ㎍/g in the muscles, 23.9-71.5 ㎍/g in the intestines, and 28.1-114.8 ㎍/g in the liver. Additionally, the toxicity profile of the detected PSTs revealed that dcGTX3 was the major component in T. pardalis and T. niphobles. When PSTs were calculated as saxitoxin equivalents the levels were all less than 0.5 ㎍/g, which is below the permitted maximum standard of 0.8 ㎍/g. These findings indicate that the toxicity of T. pardalis and T. niphobles from the southern coast of Korea is due mainly to TTX and that PSTs do not exert an effect.

• The Korean Journal of Physiology and Pharmacology
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• 제22권6호
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• pp.649-660
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• 2018

Migraine is a neurological disorder characterized by recurrent and disabling severe headaches. Although several anticonvulsant drugs that block voltagedependent $Na^+$ channels are widely used for migraine, far less is known about the therapeutic actions of carbamazepine on migraine. In the present study, therefore, we characterized the effects of carbamazepine on tetrodotoxin-resistant (TTX-R) $Na^+$ channels in acutely isolated rat dural afferent neurons, which were identified by the fluorescent dye DiI. The TTX-R $Na^+$ currents were measured in medium-sized DiIpositive neurons using the whole-cell patch clamp technique in the voltage-clamp mode. While carbamazepine had little effect on the peak amplitude of transient $Na^+$ currents, it strongly inhibited steady-state currents of transient as well as persistent $Na^+$ currents in a concentration-dependent manner. Carbamazepine had only minor effects on the voltage-activation relationship, the voltage-inactivation relationship, and the use-dependent inhibition of TTX-R $Na^+$ channels. However, carbamazepine changed the inactivation kinetics of TTX-R $Na^+$ channels, significantly accelerating the development of inactivation and delaying the recovery from inactivation. In the current-clamp mode, carbamazepine decreased the number of action potentials without changing the action potential threshold. Given that the sensitization of dural afferent neurons by inflammatory mediators triggers acute migraine headaches and that inflammatory mediators potentiate TTX-R $Na^+$ currents, the present results suggest that carbamazepine may be useful for the treatment of migraine headaches.

• 대한의생명과학회지
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• 제28권1호
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• pp.42-49
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• 2022

Tetrodotoxin (TTX) is a natural neurotoxin found in several species of puffer fish belonging to Tetraodon fugu genus and has been reported to affect processes such as proliferation, metastasis and invasion of various cancer cells. However, it was not revealed which genes were influenced by these reactions. In this experiment, it was examined in human SW620 colorectal cancer cells. The proliferation of SW620 cells was significantly reduced when treated with 0, 1, 10 and 100 μM TTX for 48 h. It was confirmed using Annexin V-propidium iodide staining that some apoptosis was induced. Differentially expressed genes (DEGs) affecting cell proliferation through RNA sequencing (RNA-seq) were selected. The expression change of DEGs was confirmed by conducting quantitative real-time polymerase chain reaction (qRT-PCR). As a result, the mRNA expression of FOS and WDR48 genes was found to be increased in the 100 μM TTX treatment group compared to the control group. On the other hand, the mRNA expression of ALKBH7, NDUFA13, RIPPLY3 and SELENOM genes was found to be reduced, and in the case of the ALKBH7 gene was identified to show significant differences. This experiment suggests that TTX can be used as an important fundamental data to elucidate the mechanism that inhibits the proliferation of SW620 cells.

• 한국수산과학회지
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• 제28권5호
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• pp.533-538
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• 1995

본 연구에서는 중국에서 수입되어 시중에서 판매되고 있는 삼채복을 시료로 하여 각 개체의 조직 부위별 독성을 조사하였고 Bio-Gel P-2 칼럼 크로마토크래피로 복어독을 부분정제하여 TLC, 전기영동 및 HPLC에 의하여 독성분을 검출하고 확인하였다. 삼채복 10개체의 경우 그 독력은 내장, 난소 및 답즙은 ND-10MU/g 및 ND-23MU/g이었으나, 간장, 껍질, 근육 및 정소는 무독하였으며, 유독개체 출현율은 난소$(100\%)$, 담즙$(20\%)$ 및 내장$(10\%)$순으로 나타났다. 간장부위는 성별에 따른 독력의 차이를 볼 수 없었으나, 생식소의 경우 성별에 따른 차이가 뚜렷하게 나타났다. 한편, 삼채복의 난소로부터 분리한 독소는 TLC와 전기영동상에서 각각 표준품 TTX와 anh-TTX의 상대이동도와 유사한 두 지점인 Rf 0.64, 0.86와 5.5, 7.2cm에서 나타내어 TTX 관련물질임이 확인되었다. 또한, HPLC분석 결과 TDA, TTX와 anh-TTX의 peak가 뚜렷하게 나타난 반면 4-epi TTX의 peak도 약간 나타났다.

• 대한임상독성학회지
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• 제9권2호
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• pp.95-100
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• 2011

Purpose: Ingestion of puffer fish can be poisonous due to the presence of potent neurotoxins such as tetrodotoxin (TTX) found in its tissues. There are few clinical reports related to TTX. We performed this study to evaluate the clinical characteristics of TTX poisoning. Methods: We conducted a retrospective study of the 41 patients diagnosed with TTX poisoning who visited the Seoul Asan medical center from July 2004 and December 2010. A review of patients' electronic medical records and patient telephone interviews were conducted. Diagnosis of TTX poisoning was confirmed by observing the casual link between puffer fish consumption and the development of typical TTX intoxication symptoms. Results: The mean age of the patients included in the study was 46.6 years. The highest incidence of intoxication was observed in patients in their 50s (10 patients). Seasonal distribution of intoxication events included 10 in spring, 7 in summer, 10 in fall, and 14 in winter. In most cases, symptoms occurred within 1 hour of ingestion. A wide range of symptoms were associated with puffer fish ingestion affecting multiple body systems including neuromuscular (27 patients), gastrointestinal (19 patients), and cardiopulmonary/vascular (19 patients). All patients were treated with symptomatic and supportive therapy and recovered completely, without sequelae, within 48 hours. In three cases, ventilator support was required. Conclusion: TTX poisoning is not seasonally related, and patients admitted to the emergency room were observed with a wide range of symptoms. Where TTX poisoning is diagnosed, supportive therapy should be performed. Early intubation and ventilation is important, especially is cases of respiratory failure.

• 한국식품영양학회지
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• 제9권4호
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• pp.361-365
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• 1996

인도네시아산 흰밀복 10마리와 중국산 황복 9마리의 근육, 껍질, 간장, 내장 및 난소 등의 조직별 독성을 조사하였다. 또한, 간장 독소성분을 Bio-gel P-2 컬럼 크로마토크래피로 분리하여 TLC, 전기영동, HPLC로 분석하였다. 흰 밀복의 간장은 무독하였고 내장은 무독 내지 약독으로 나타났고, 평균 독력은 각각 5.5$\pm$0.9와 11.8$\pm$4.2 MU/g이었다. 그리고 근육과 껍질부위의 평균독력은 각각 3.0$\pm$0.8과 2.2$\pm$0.1 MU/g이었다. 황복의 부위별 독성은 담즙, 난소, 정소 및 간장이 각각 9~200, 40~133, 13~186 및 6~210 MU/g으로 나타났다. 껍질 및 근육부위는 3~34 MU/g와 2~44 MU/g으로 비식용부위 보다는 낮았다. 각 부위의 유독개체 출현율은 난소(100%), 내장(100%), 담즙(89%), 간장(78%), 껍질(67%), 정소(33%) 및 근육(11%)의 순서로 나타났다. 흰 밀복과 황복의 간장으로부터 분리한 독소는 TLC로 분석한 결과 TTX 및 anhydro-TTX로 동정되는 2개의 TTX spot을 검출하였고, 전기영동에서도 마찬가지 결과를 얻었다. 또한, HPLC의 분석결과와 TTX와 anhydro-TTX와 같은 위치의 피크를 나타냈다. 황복은 표준물질 TTX, 4-epi-TTX 및 anh-TTX의 세 피크를 나타냈다.

• 혜화의학회지
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• 제28권2호
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• pp.1-11
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• 2019

Objective: The aim of this study is to analyze the previously published research articles related to puffer fish toxin focusing on tumor. Method: Literatures were searched in PubMed database, published since 2000, using the keyword; Puffer fish, Fugu and tetrodotoxin (TTX) with cancer or tumor. Research papers were classified by year, country, study model, used material, kind of tumor and study subject. Finally, a total of 41 studies were analyzed in this study. Results: From 2000 to 2018, the most abundant papers were published in 2009 (6 studies) and almost half of the papers were studied in United Kingdom (20 studies). The 39 studies used TTX purified from puffer fish while 2 studies used crude extract of skin and gonad of puffer fish. The most used target cell line was prostate cancer (15 studies), and the next was breast cancer (14 studies). The study methods were classified into 4 clinical studies, 2 animal studies and 35 cell-based studies. Conclusions: Our results show that the overview of cancer-related studies using puffer fish poison. This information would be helpful for the puffer fish-derived drug researches in the future.

• Journal of Microbiology and Biotechnology
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• 제27권4호
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• pp.725-730
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• 2017

A heteronemertean, Yininemertes pratensis, was collected in Han River Estuary, South Korea. This estuarine nemertean has been known by the local fishermen for harmful effects to the glass eels, juveniles of Japanese eel Anguilla japonica, migrating to fresh water. The present study confirmed the neurotoxic effects of this heteronemertean ribbon worm at the cellular level. Derivative types of neurotoxic tetrodotoxin (TTX), 5,11-dideoxy TTX (m/z 288) and 11-norTTX-6(S)-01 (m/z 305.97), were identified through HPLC and MALDI-TOF MS. However, significant neurotoxicity was confirmed in the fraction containing an undefined molecule corresponding to the 291.1 (m/z) peak, when tested in rat primary astrocytes and dorsal ganglion cells. This study is the first to report neurotoxins of the estuarine nemertean, fairly abundant in the Han River estuary, and suggests the long-term monitoring of population dynamics and surveillance of the toxicity in this river estuary.

• 한국수산과학회지
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• 제23권3호
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• pp.263-265
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• 1990