Toxins of Pufferfish—Distribution, Accumulation　Mechanism, and Physiologic Functions

Abstract

Keywordsunit) is defined as the amount of toxin required to kill a 20-g male mouse within 30 min after intraperitoneal administration], and the minimum lethal dose (MLD) for humans is estimated to be approximately 10000 MU (ª2 mg) (Noguchi and Ebesu 2001).The main symptoms of human intoxication include numbness of lips, tongue and the limbs, paresthesia, dysarthria, respiratory distress, and death is caused by respiratory failure in the most critical cases (Noguchi and Ebesu 2001). According to Toda et al. (2012), 651 incidents of TTX poisoning due to pufferfish have occurred in Japan, involving 976 patients and 56 deaths during the 22 years from 1989 to 2010. Many cases occurred during the winter season in coastal prefectures of the Seto Inland Sea, with "komonfugu" Takifugu poecilonotus, "mafugu" Takifugu porphyreus, "higanfugu" Takifugu pardalis, "shosaifugu" Takifugu Abstract Our many years of studies have provided a lot of information regarding distribution, accumulation mechanism, and physiologic functions of the natural toxins harbored by pufferfish. We detected tetrodotoxin (TTX) and/or its derivatives in several species of aquatic organisms including marine bacteria. This, along with the fact that pufferfish became non-toxic when they were reared with non-toxic feed, indicated that the toxification of pufferfish is of exogenous origin. Subsequently, we revealed by various TTX administration experiments using non-toxic cultured pufferfish that the TTX administered into the muscle or digestive tract rapidly transferred to the liver and skin, and that the toxin transfer to the gonads was largely different between male and female, suggesting the involvement of maturation in the internal kinetics of TTX. On the other hand, we visualized micro-distribution of TTX in the tissues of various TTX-bearing organisms using an immunohistochemical technique, giving a crucial insight to elucidate physiologic functions of TTX including the function as a defensive or offensive agent. Furthermore, we found that Southeast Asian freshwater pufferfish possess paralytic shellfish poison (PSP) as a main toxin, and that boxfish and Bangladeshi freshwater pufferfish bear a palytoxin (PLTX)-like toxin, and cause a rhabdomyolysis, which overturned the common sense that pufferfish toxin equals TTX.

An Updated Review of Tetrodotoxin and Its Peculiarities

“…Their extracts were analyzed by LC-MS/MS and were found to contain the parent TTX, at levels of 93 ng and 88 ng TTX per liter of culture, respectively [52]. Certain works supporting an entirely endogenous origin of TTX even support that, in the case of some pufferfish species, where TTX plays a defense mechanism role, extant bacteria are not involved anymore in TTX biosynthesis, despite the initial bacterial origin of their biosynthetic genes [56]. Notably though, TTX is not present in exclusively freshwater-living fauna, not returning to aqueous systems for breeding reasons [57], which may also point to an association of TTX production with marine bacteria.…”

“…Nevertheless, some scientific evidence strongly indicate the exogenous toxification of aquatic organisms as a valid theory [56], that is: (1) the remarkable individual and regional variations in pufferfish toxicity, (2) TTX accumulation by the trumpet shell Charonia sauliae through ingestion of toxic starfish, and (3) TTX absence in artificially cultured pufferfish Takifugu rubripes and T. niphobles when fed non-toxic diets, in contrast to their ability for efficient accumulation following oral TTX administration. In this context, it is suggested that aquatic organisms, such as pufferfish, do not synthesize TTX, but acquire it instead from other toxic organisms bearing bioconcentrated TTX through the food chain with marine bacteria being at the start [58].…”

Tetrodotoxin/Saxitoxins Selectivity of the Euryhaline Freshwater Pufferfish Dichotomyctere fluviatilis

“…Tetrodotoxin (TTX), a potent neurotoxin, is the main toxin component of marine pufferfish of the genus Takifugu, including Takifugu rubripes and Takifugu pardalis, which inhabit the coastal waters of Japan [1][2][3]. Organs such as the liver, ovary, and, in some species, the skin, are generally highly toxic, while the muscle and testes are nontoxic or only weakly toxic [2,4,5].…”

Accumulation and Elimination of Tetrodotoxin in the Pufferfish Takifugu obscurus by Dietary Administration of the Wild Toxic Gastropod Nassarius semiplicata

“…Previous studies have suggested that TTX may be initially synthesized by marine bacteria and transferred to pufferfish via the food chain [2,18]. Nevertheless, the mechanisms of TTX accumulation in the pufferfish through a toxic food chain, and its elimination remains to be elucidated [19].…”