title: Examination of transformation among tetrodotoxin and its analogs in the living cultured juvenile puffer fish, kusafugu, Fugu niphobles by intramuscular administration.
abstract: In puffer fish, tetrodotoxin (TTX) exists as the major toxin with chemically equilibrium analogs (4-epiTTX, 4,9-anhydroTTX) and chemically non-equilibrium analogs (deoxy analogs, 11-oxoTTX, 4-S-cysteinylTTX). There are two purposes to this study: 1) to search for the reason why TTX is the most major analog in puffer fish, even 4,9-anhydroTTX is chemically more stable, 2) to investigate whether or not chemically non-equilibrium analogs are transformed in puffer fish, because these were predicted to be biosynthetic intermediates. Pure TTX, 4-epiTTX, 4,9-anhydroTTX, and 11-oxoTTX were separately administrated to the cultured non-toxic juvenile puffer fish kusafugu, Fugu niphobles by intramuscular injection. Sixteen days after administration, TTX analogs in the whole fish were analyzed by LC-fluorescent detection and LC/MS. By the administration of TTX, 4-epiTTX, and 4,9-anhydroTTX, 34-40% of the administrated doses of the toxins were accumulated, and 4,9-anhydroTTX has become the major toxin after inter-conversion. This result indicates discrepancy from the previous ones wherein TTX was predominantly accumulated when TTXs were administrated through diets; this suggests that dietary administration might be necessary to accumulate TTX as the major toxin, and not 4,9-anhydroTTX. Transformations from TTX to deoxy analogs or 11-oxoTTX, or from 11-oxoTTX to TTX were not detected in this study.
authors.affiliation: Fisheries Research Laboratory, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 2971-4 Maisaka-cho Nishi-ku Hamamatsu, Shizuoka 431-0214, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kono
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsui
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Furukawa
authors.forename: Takuhiko
authors.initials: T
authors.lastname: Takase
authors.forename: Kunio
authors.initials: K
authors.lastname: Yamamori
authors.forename: Hideko
authors.initials: H
authors.lastname: Kaneda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Jang
authors.forename: Mari
authors.initials: M
authors.lastname: Yotsu-Yamashita
mesh_terms: D000818:Animals; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D007273:Injections, Intramuscular; D023721:Tetraodontiformes / Q000378:metabolism*; D013779:Tetrodotoxin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism
chemical_list: C504323:4-S-cysteinyltetrodotoxin; C104261:11-oxotetrodotoxin; C047739:anhydrotetrodotoxin; D013779:Tetrodotoxin; C047738:4-epitetrodotoxin; D003545:Cysteine