Studies on pharmacokinetics of tetrodotoxin in the puffer fish and tetrodotoxin-transporter in the liver

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Puffer fish, the family Tetraodontidae, contain a potent neurotoxin, tetrodotoxin (TTX) in high level in the specific tissues such as liver and ovary. However, the underlying mechanism of puffer fish toxification is still unclear. This study examined the pharmacokinetics of TTX in the puffer fish Takifugu rubripes by a single administration and demonstrated that TTX is absorbed into the systemic circulation from the gastrointestinal tract by saturable mechanism and finally accumulated in the liver. In vitro equilibrium dialysis revealed that TTX non-specifically binds to plasma proteins and exists predominately in the unbound form in the circulating blood of the puffer fish. Moreover, we examined hepatic gene expression profile of the puffer fish by suppression subtracted hybridization in response to the intramuscular administration of TTX. The administration of TTX increased the gene expression of the acute-phase response proteins in the liver as well as the genes related to transporters.