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Pufferfish Poisoning and Tetrodotoxin

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Marine and Freshwater Toxins

Part of the book series: Toxinology ((TOXI))

Abstract

Pufferfish possess a potent neurotoxin, tetrodotoxin (TTX), and have caused human intoxications all over the world, especially in East Asia, where people have a time-honored food culture of eating pufferfish. TTX is distributed over a wide variety of organisms including flatworms, ribbon worms, mollusks, crustaceans, starfish, fish, and amphibians, and in the East Asian or Southeast Asian countries, TTX poisonings due to marine snails, horseshoe crabs, and gobies have also occasionally occurred, suggesting the possibility of further geographic expansion and/or diversification of TTX-bearing organisms caused by a change in the marine environment. The origin of TTX is likely certain species of marine bacteria, and many TTX-bearing organisms are toxified via the food chain that starts with the bacteria. Recently, valuable information regarding the dynamics of TTX taken up into the pufferfish body through food organisms, and the molecular mechanisms involved is accumulating, while TTX-bearing organisms are assumed to utilize TTX effectively for their survival, although TTX is a fatal toxin to organisms that possess no TTX. The present chapter describes the distribution of TTX in metazoans, and then introduces recent studies to clarify the intake of TTX to pufferfish liver using a pharmacokinetic model, and to reveal the transfer profile of TTX in pufferfish based on several TTX administration experiments. Moreover, after discussing on the potential physiologic functions of TTX in TTX-bearing organisms such as defense, offense, and attraction, human intoxications due to TTX will be summarized.

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References

  • Arakawa O, Hwang DF, Taniyama S, Takatani T. Toxins of pufferfish that cause human intoxications. In: Ishimatsu A, Lie HJ, editors. Coastal environmental and ecosystem issues of the East China Sea. Tokyo: Nagasaki University/TERRAPUB; 2010.

    Google Scholar 

  • Bentur Y, Ashkar J, Lurie Y, Levy Y, Azzam ZS, Limanovich M, Golik M, Gurevych B, Golani D, Eisenman A. Lessepsian migration and tetrodotoxin poisoning due to Lagocephalus sceleratus in the eastern Mediterranean. Toxicon. 2008;52:964–8.

    Article  CAS  PubMed  Google Scholar 

  • Brillantes S, Samosorn W, Faknoi S, Oshima Y. Toxicity of puffers landed and marketed in Thailand. Fish Sci. 2003;69:1224–30.

    Article  CAS  Google Scholar 

  • Chau R, Kalaitzis JA, Neilan BA. On the origins and biosynthesis of tetrodotoxin. Aquat Toxicol. 2011;104:61–74.

    Article  CAS  PubMed  Google Scholar 

  • Cohen NJ, Deeds JR, Wong ES, Hanner RH, Yancy HF, White KD, Thompson TM, Wahl M, Pham TD, Guichard FM, Huh I, Austin C, Dizikes G, Gerber SI. Public health response to puffer fish (tetrodotoxin) poisoning from mislabeled product. J Food Protect. 2009;72:810–7.

    CAS  Google Scholar 

  • Hanifin CT. The chemical and evolutionary ecology of tetrodotoxin (TTX) toxicity in terrestrial vertebrates. Mar Drugs. 2010;8:577–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Honda S, Arakawa O, Takatani T, Tachibana K, Yagi M, Tanigawa A, Noguchi T. Toxification of cultured puffer fish Takifugu rubripes by feeding on tetrodotoxin-containing diet. Nippon Suisan Gakkaishi. 2005a;71:815–20.

    Article  CAS  Google Scholar 

  • Honda S, Ichibu T, Arakawa O, Takatani T, Tachibana K, Yagi M, Tanigawa A, Noguchi T. Antibody productivity against sheep red blood cells and splenocyte proliferation reaction of tiger puffer (Takifugu rubripes) fed with tetrodotoxin-containing diets. Aquac Sci. 2005b;53:205–10.

    Google Scholar 

  • Hwang DF, Noguchi T. Tetrodotoxin poisoning. Adv Food Nat Res. 2007;52:141–236.

    Article  CAS  Google Scholar 

  • Hwang PA, Tsai YH, Lin SJ, Hwang DF. The gastropods possessing TTX and/or PSP. Food Rev Int. 2007;23:321–40.

    Article  CAS  Google Scholar 

  • Ikeda K, Murakami Y, Emoto Y, Ngy L, Taniyama S, Yagi M, Takatani T, Arakawa O. Transfer profile of intramuscularly administered tetrodotoxin to nontoxic cultured specimens of the pufferfish Takifugu rubripes. Toxicon. 2009;53:99–103.

    Article  CAS  PubMed  Google Scholar 

  • Ikeda K, Emoto Y, Tatsuno R, Wang JJ, Ngy L, Taniyama S, Takatani T, Arakawa O. Maturation-associated changes in toxicity of the pufferfish Takifugu poecilonotus. Toxicon. 2010;55:289–97.

    Article  CAS  PubMed  Google Scholar 

  • Isbister GK, Son J, Wang F, Maclean CJ, Lin CSY, Ujma J, Balit CR, Smith B, Milder DG, Kiernan MC. Pufferfish poisoning: a potentially life-threatening condition. MJA. 2002;177:650–3.

    PubMed  Google Scholar 

  • Islam QT, Razzak MA, Islam MA, Bari MI, Basher A, Chowdhury FR, Sayeduzzaman ABM, Ahasan HAMN, Faiz MA, Arakawa O, Yotsu-Yamashita M, Kuch U, Mebs D. Puffer fish poisoning in Bangladesh: clinical and toxicological results from large outbreaks in 2008. Transact R Soc Trop Med Hyg. 2011;105:74–80.

    Article  CAS  Google Scholar 

  • Itoi S, Yoshikawa S, Asahina K, Suzuki M, Ishizaka K, Takimoto N, Mitsuoka R, Yokoyama N, Detake A, Takayanagi C, Eguchi M, Tatsuno R, Kawane M, Kokubo S, Takanashi S, Miura A, Suitoh K, Takatani T, Arakawa O, Sakakura Y, Sugita H. Larval pufferfish protected by maternal tetrodotoxin. Toxicon. 2014;78:35–40.

    Article  CAS  PubMed  Google Scholar 

  • Kanchanapongkul J. Tetrodotoxin poisoning following ingestion of the toxic eggs of the horseshoe crab Carcinoscorpius rotundicauda, a case series from 1994 through 2006. Southeast Asian J Trop Med Public Health. 2008;39:303–6.

    PubMed  Google Scholar 

  • Kanoh S, Noguchi T, Kamimura S, Hashimoto K. A survey of toxicity of the pufferfish, Fugu pardalis, inhabiting the Sanriku coast. J Food Hyg Soc Japan. 1984;25:24–9.

    Article  Google Scholar 

  • Kodama M, Ogata T, Kawamukai K, Oshima Y, Yasumoto T. Toxicity of muscle and other organs of five species of puffer collected from the Pacific coast of Tohoku area of Japan. Nippon Suisan Gakkaishi. 1984;50:703–6.

    Article  Google Scholar 

  • Kono M, Matsui T, Furukawa K, Yotsu-Yamashita M, Yamamori K. Accumulation of tetrodotoxin and 4,9-anhydrotetrodotoxin in cultured juvenile kusafugu Fugu niphobles by dietary administration of natural toxic komonfugu Fugu poecilonotus liver. Toxicon. 2008;51:1269–73.

    Article  CAS  PubMed  Google Scholar 

  • Leung KSY, Fong BMW, Tsoi YK. Analytical challenges: determination of tetrodotoxin in human urine and plasma by LC-MS/MS. Mar Drugs. 2011;9:2291–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mahmud Y, Okada K, Takatani T, Kawatsu K, Hamano Y, Arakawa O, Noguchi T. Intra-tissue distribution of tetrodotoxin in two marine puffers Takifugu vermicularis and Chelonodon patoca. Toxicon. 2003;41:13–8.

    Article  CAS  PubMed  Google Scholar 

  • Matsui T, Hamada S, Konosu S. Difference in accumulation of puffer fish toxin and crystalline tetrodotoxin in the puffer fish, Fugu rubripes rubripes. Nippon Suisan Gakkaishi. 1981;47:535–7.

    Article  CAS  Google Scholar 

  • Matsui T, Sato H, Hamada S, Shimizu C. Comparison of toxicity of the cultured and wild puffer fish Fugu niphobles. Nippon Suisan Gakkaishi. 1982;48:253.

    Google Scholar 

  • Matsumoto T, Nagashima Y, Kusuhara H, Ishizaki S, Shimakura K, Shiomi K. Pharmacokinetics of tetrodotoxin in puffer fish Takifugu rubripes by a single administration technique. Toxicon. 2008a;51:1051–9.

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto T, Nagashima Y, Kusuhara H, Ishizaki S, Shimakura K, Shiomi K. Evaluation of hepatic uptake clearance of tetrodotoxin in the puffer fish Takifugu rubripes. Toxicon. 2008b;52:369–74.

    Article  CAS  PubMed  Google Scholar 

  • Matsumura K. Tetrodotoxin as a pheromone. Nature. 1995;378:563–4.

    Article  CAS  PubMed  Google Scholar 

  • McNabb P, Selwood AI, Munday R, Wood SA, Taylor DI, MacKenzie LA, Ginkel R, Rhodes LL, Cornelisen C, Heasman K, Holland PT, King C. Detection of tetrodotoxin from the grey side-gilled sea slug Pleurobranchaea maculate, and associated dog neurotoxicosis on beaches adjacent to the Hauraki Gulf, Auckland, New Zealand. Toxicon. 2010;56:466–73.

    Article  CAS  PubMed  Google Scholar 

  • Miyazawa K, Noguchi T. Distribution and origin of tetrodotoxin. J Toxicol Toxin Rev. 2001;20:11–33.

    Article  CAS  Google Scholar 

  • Moczydlowski EG. The molecular mystique of tetrodotoxin. Toxicon. 2013;63:165–83.

    Article  CAS  PubMed  Google Scholar 

  • Nagashima Y, Mataki I, Toyoda M, Nakajima H, Tsumoto K, Shimakura K, Shiomi K. Change in tetrodotoxin content of puffer fish Takifugu rubripes during seed production from fertilized eggs to juveniles. Food Hyg Saf Sci. 2010;51:48–51.

    Article  CAS  Google Scholar 

  • Nagashima Y, Matsumoto T, Kadoyama K, Ishizaki S, Terayama M. Toxicity and molecular identification of green toadfish Lagocephalus lunaris collected from Kyushu coast, Japan. J Toxicol. 2011; Article ID 801285.

    Google Scholar 

  • Nakamura M, Yasumoto T. Tetrodotoxin derivatives in puffer fish. Toxicon. 1985;23:271–6.

    Article  CAS  PubMed  Google Scholar 

  • Narahashi T. Pharmacology of tetrodotoxin. J Toxicol Toxin Rev. 2001;20:67–84.

    Article  CAS  Google Scholar 

  • Nieto FR, Cobos EJ, Tejada MA, Sanchez-Fernandez C, Gonzalez-Canao R, Cendan CM. Tetrodotoxin (TTX) as a therapeutic agent for pain. Mar Drugs. 2012;10:281–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noguchi T, Arakawa O. Tetrodotoxin- distribution and accumulation in aquatic organisms, and cases of human intoxication. Mar Drugs. 2008;6:220–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noguchi T, Ebesu JSM. Puffer poisoning: epidemiology and treatment. J Toxicol Toxin Rev. 2001;20:1–10.

    Article  CAS  Google Scholar 

  • Noguchi T, Arakawa O, Takatani T. Toxicity of pufferfish Takifugu rubripes cultured in netcages at sea or aquaria on land. Comp Biochem Physiol D. 2006;1:153–7.

    Google Scholar 

  • Noguchi T, Onuki K, Arakawa O. Tetrodotoxin poisoning due to pufferfish and gastropods, and their intoxication mechanism. ISRN Toxicol. 2011; 2011: Article ID 276939, 10 pages.

    Google Scholar 

  • Okita K, Takatani T, Nakayasu J, Yamazaki H, Sakiyama K, Ikeda K, Arakawa O, Sakakura Y. Comparison of the localization of tetrodotoxin between wild pufferfish Takifugu rubripes juveniles and hatchery-reared juveniles with tetrodotoxin administration. Toxicon. 2013a;71:128–33.

    Article  CAS  PubMed  Google Scholar 

  • Okita K, Yamazaki H, Sakiyama K, Yamane H, Niina S, Takatani T, Arakawa O, Sakakura Y. Puffer smells tetrodotoxin. Ichthyol Res. 2013b;60:386–9.

    Article  Google Scholar 

  • Saito T, Kageyu K, Goto H, Murakami K, Noguchi T. Tetrodotoxin attracts pufferfish (“torafugu” Takifugu rubripes). Bull Inst Oceanic Res Develop Tokai Univ. 2000;21:93–6.

    Google Scholar 

  • Shimizu D, Sakiyama K, Sakakura Y, Takatani T, Takahashi Y. Quantitative evaluation of post-release mortality using salt pond mesocosms: case studies of hatchery and wild juvenile tiger puffer. Rev Fish Sci. 2008;16:195–203.

    Article  Google Scholar 

  • Silva CCP, Zannin M, Rodrigues DS, Santos CR, Correa IA, Haddad Jr V. Clinical and epidemiological study of 27 poisonings caused by ingesting puffer fish (Tetraodontidae) in the states of Santa Catarina and Bahia, Brazil. Rev Inst Med Trop S Paulo. 2010;52:8.

    Google Scholar 

  • Silva M, Azevedo J, Rodriguez P, Alfonso A, Botana LM, Vasconcelos V. New gastropod vectors and tetrodotoxin potential expansion in temperate waters of the Atlantic Ocean. Mar Drugs. 2012;10:712–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanu MB, Mahmud Y, Arakawa O, Takatani T, Kajihara H, Kawatsu K, Hamano Y, Asakawa M, Miyazawa K, Noguchi T. Immunoenzymatic visualization of tetrodotoxin (TTX) in Cephalothrix species (Nemertea: Anopla: Palaeonemertea: Cephalotrichidae) and Planocerareticulata (Platyhelminthes: Turbellaria: Polycladida: Planoceridae). Toxicon. 2004;44:515–20.

    Article  CAS  PubMed  Google Scholar 

  • Tatsuno R, Shikina M, Soyano K, Ikeda K, Takatani T, Arakawa O. Maturation-associated changes in the internal distribution of tetrodotoxin in the female goby Yongeichthys criniger. Toxicon. 2013;63:64–9.

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Araki T, Tatsuno R, Nina S, Ikeda K, Hamasaki M, Sakakura Y, Takatani T, Arakawa O. Transfer profile of intramuscularly administered tetrodotoxin to artificial hybrid specimens of pufferfish, Takifugu rubripes and Takifugu niphobles. Toxicon. 2011;58:565–9.

    Article  CAS  PubMed  Google Scholar 

  • Williams BL. Behavioral and chemical ecology of marine organisms with respect to tetrodotoxin. Mar Drugs. 2010;8:381–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamamori K, Nakamura M, Matsui T, Hara T. Gustatory responses to tetrodotoxin and saxitoxin in fish: a possible mechanism for avoiding marine toxins. Can J Fish Aquat Sci. 1988;45:2182–6.

    Article  CAS  Google Scholar 

  • Yamamori K, Kono M, Furukawa K, Matsui T. The toxification of juvenile cultured kusafugu Takifugu niphobles by oral administration of crystalline tetrodotoxin. J Food Hyg Soc Japan. 2004;45:73–5.

    Article  CAS  Google Scholar 

  • Yotsu-Yamashita M. Chemistry of puffer fish toxin. J Toxicol Toxin Rev. 2001;20:51–66.

    Article  CAS  Google Scholar 

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Correspondence to Yuji Nagashima .

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Nagashima, Y., Arakawa, O. (2016). Pufferfish Poisoning and Tetrodotoxin. In: Gopalakrishnakone, P., Haddad Jr., V., Tubaro, A., Kim, E., Kem, W. (eds) Marine and Freshwater Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6419-4_12

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