Tetrodotoxin, an Extremely Potent Marine Neurotoxin: Distribution, Toxicity, Origin and Therapeutical Uses

Abstract

Tetrodotoxin (TTX) is a potent neurotoxin responsible for many human intoxications and fatalities each year. The origin of TTX is unknown, but in the pufferfish, it seems to be produced by endosymbiotic bacteria that often seem to be passed down the food chain. The ingestion of contaminated pufferfish, considered the most delicious fish in Japan, is the usual route of toxicity. This neurotoxin, reported as a threat to human health in Asian countries, has spread to the Pacific and Mediterranean, due to the increase of temperature waters worldwide. TTX, for which there is no known antidote, inhibits sodium channel producing heart failure in many cases and consequently death. In Japan, a regulatory limit of 2 mg eq TTX/kg was established, although the restaurant preparation of “fugu” is strictly controlled by law and only chefs qualified are allowed to prepare the fish. Due to its paralysis effect, this neurotoxin could be used in the medical field as an analgesic to treat some cancer pains.

Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL)

“…In fatal cases, humans show neurological signs within 2–3 h after exposure followed by death within 7–8 h due to respiratory failure and cardiovascular collapse [17]. Even though most intoxicated people should fully recover usually within 24 h [13], it was also reported that death may occur in less than 30 min [18], indicating a rapid rate of absorption from the gastrointestinal tract. Although hundreds of TTX intoxication cases have been published [19] it is difficult to find a correlation between toxin concentration and poisoning symptoms due to the scarce oral toxicity data.…”

“…TTX is unequivocally toxic to mammals. In mice, the reported LD 50 values were 2–10, 10–10.7, 12.5–16 µg/kg BW for intravenous, intraperitoneal i.p., and subcutaneous administration, respectively [13,14]. However, at present there are no oral toxicity data of purified TTX.…”

“…It blocks sodium channels [9,10] and terminates nerve conduction and muscle action potentials [11], leading to progressive paralysis and, in extreme cases, to death from respiratory and heart failure [12,13]. …”

The association of bacterial C9-based TTX-like compounds with Prorocentrum minimum opens new uncertainties about shellfish seafood safety

“…However, the origin of TTX is still unclear, although the presence of this toxin in such a diverse group of animals suggests that bacteria might be as the primary source13. In this sense, TTX can be produced without bacteria, but the presence of microorganisms could, in some way, simplify TTX biosynthesis11.…”

Potentially dangerous fish of the Paraiba Estuary: Identification and envenomation mechanisms

“…The poisonous pufferfishes can accumulate tetrodotoxin, which is the principal neurotoxin found in pufferfish [7,22]. For a long time, tetrodotoxin was considered a metabolic product of fishes [23], but studies have demonstrated that certain bacteria, such as Vibrio sp., produce the toxin and are incorporated into fishes through the food chain [23,24].…”