Distribution of tetrodotoxin and its analogs in the toxic flatworm Planocera multitentaculata from Honshu Island, Japan

Abstract

Tetrodotoxin (TTX), one of the most potent naturally occurring neurotoxins, has been detected in both marine and terrestrial organisms. The marine polyclad flatworm Planocera multitentaculata is known to contain high levels of TTX throughout its life cycle, including in the egg and larval stages. We recently reported that P. multitentaculata from the coastal area of Hayama, Kanagawa, Japan, possesses TTX analogs including 5,6,11-trideoxyTTX, monodeoxyTTXs, dideoxyTTXs, and 11-norTTX-6(S)-ol. It is not known whether all P. multitentaculata occurring in the Japanese archipelago possess major TTX analogs, or whether regional variations in TTX profile exist. In this study, we used high-resolution liquid chromatography–mass spectrometry to investigate the content profile of TTX and its analogs in P. multitentaculata collected from several regions of the Japanese coast. We detected TTX and its major analogs 5,6,11-trideoxyTTX, dideoxyTTXs, monodeoxyTTXs, and 11-norTTX-6(S)-ol in all specimens regardless of the sampling site. In addition, their relative proportions showed a similar pattern. These results suggest that the flatworm may have mechanisms involved in maintaining the proportions of TTX and its analogs in the body. How the toxic flatworms acquire the highly concentrated toxins and maintain the proportions of TTXs is therefore of great interest and further investigation.

Japanese Planocerid Flatworms: Difference in Composition of Tetrodotoxin and Its Analogs and the Effects of Ingestion by Toxin-Bearing Fishes in the Ryukyu Islands, Japan

“…In the present study, it was shown that compositions of TTX and analogs in Planocera sp. and P. reticulata were identical to those seen in P. multitentaculata (Suo et al 2022 , 2024 ). On the other hand, none of the TTX and analogs were detected in P. pellucida , which is closely related to these toxic flatworms but is not known to possess TTX (Kashitani et al 2020 ).…”

“…Recently, it has been reported that P. multitentaculata possess a variety of TTX analogs, including dideoxyTTXs, deoxyTTXs, and 11-norTTX-( S )-ol, in addition to large amounts of TTX and 5,6,11-trideoxyTTX (Suo et al 2022 ). Although the internal localization of these TTX analogs in the flatworm changes during growth (Oyama et al 2022 ), there is no difference in the composition of TTX analogs between samples collected in different sites (Suo et al 2024 ), indicating that the flatworm might possess biosynthetic processes of TTX in the body. On the other hand, there is no information on TTX analogs in planocerid flatworms, with the exception of the planocerid in Guam (Ritson-Williams et al 2006 ) and P. multitentaculata as mentioned (Suo et al 2022 , 2024 ).…”

“…The 5,6,11-trideoxyTTX has been reported to be dominantly high in a variety of organisms (Rambla-Alegre et al 2017 ; Suo et al 2021 , 2022 , 2024 ; Ito et al 2022 , 2023 ; Vlasenko and Magarlamov 2020 , 2022 ). Recently, TTX/5,6,11-trideoxyTTX ratios of pufferfish, including C. patoca , collected throughout the Japanese Archipelago, ranged from 2 to 5 regardless of species or region.…”