Tetrodotoxin

From Dog

Tetrodotoxins and saxitoxins are naturally found in puffer fish[2], porcupine fish, ocean sunfish, trigger fish, sea slugs, toads, blue-ringed octopus and ribbon worms[3].

This toxin is a potent neurotoxin (LD50 332 μg/kg)[4] with no known antidote.

Tetrodotoxin is produced by commensal bacteria which reside within the gastrointestinal tract of these organism. The toxin is then transferred into the liver and skin of the fish, where it resides[5].

Tetrodotoxin blocks action potentials in nerves by binding to the voltage-gated, fast sodium channels in nerve cell membranes, particularly the brain[6] and heart[7].

Poisoning in dogs is usually associated with consumption of raw puffer fish, sea slugs or other marine fish, or inhalation or skin contact with poisonous toads. It is commonly reported in Japan, Gulf of Mexico and New Zealand[8].

Signs of intoxication are primarily asymptomatic in small doses, but neurological signs can occur within 1 - 3 hours post-ingestion, with symptoms such as paraesthesiae, dyspnea, ataxia, ptyalism and seizures[9] have been reported, associated with a higher mortality rates due to respiatory and cardiac failure[10][11].

Symptoms include tremors, hyperesthesia, muscle fasciculation, seizures, nystagmus and diarrhea.

Diagnosis is based on history of exposure or presence of fish in vomitus. A definitive diagnosis requires chemical testing of vomitus or tissue sample testing taken from postmortem samples.

A differential diagnosis would include ciguatera poisoning.

Treatment involves decontamination and supportive therapy for seizures (e.g. diazepam, phenobarbital), tremors and muscle fasciculation. Severe cases will require induction of general anesthesia with thiopentone and artificial ventilation and aggressive intravenous fluid therapy.

Use of fampridine has shown to improve clinical responses[12].

An experimental monoclonal antibody against tetrodotoxin has been developed with purported efficacy against clinical symptoms in mice[13].

References

  1. Seaslug forum
  2. Tatsuno R et al (2013) RT-PCR- and MALDI-TOF mass spectrometry-based identification and discrimination of isoforms homologous to pufferfish saxitoxin- and tetrodotoxin-binding protein in the plasma of non-toxic cultured pufferfish (Takifugu rubripes). Biosci Biotechnol Biochem 77(1):208-212
  3. Asakawa M et al (2013) Highly toxic ribbon worm Cephalothrix simula containing tetrodotoxin in Hiroshima Bay, Hiroshima Prefecture, Japan. Toxins (Basel) 5(2):376-395
  4. Moczydlowski EG (2013) The molecular mystique of tetrodotoxin. Toxicon 63:165-183
  5. Tatsuno R et al (2013) Change in the transfer profile of orally administered tetrodotoxin to non-toxic cultured pufferfish Takifugu rubripes depending of its development stage. Toxicon 65:76-80
  6. Ghosh A et al (2013) Somatotopic astrocytic activity in the somatosensory cortex. Glia 61(4):601-610
  7. Scornik FS et al (2006) Functional expression of "cardiac-type" Nav1.5 sodium channel in canine intracardiac ganglia. Heart Rhythm 3(7):842-850
  8. McNabb P et al (2010) Detection of tetrodotoxin from the grey side-gilled sea slug - Pleurobranchaea maculata, and associated dog neurotoxicosis on beaches adjacent to the Hauraki Gulf, Auckland, New Zealand. Toxicon 56(3):466-473
  9. Galanopoulou AS (2013) Basic mechanisms of catastrophic epilepsy - Overview from animal models. Brain Dev Jan 10
  10. Trevett AJ et al (1997) Tetrodotoxic poisoning from ingestion of a porcupine fish (Diodon hystrix) in Papua New Guinea: nerve conduction studies. Am J Trop Med Hyg 56(1):30-32
  11. Peacock, RE et al (2012) Aplysia gigantea toxicosis in 72 dogs. AEC, Spring newsletter. pp:1
  12. Olby NJ et al (2009) Pharmacokinetics of 4-aminopyridine derivatives in dogs. J Vet Pharmacol Ther 32(5):485-491
  13. Rivera VR et al (1995) Prophylaxis and treatment with a monoclonal antibody of tetrodotoxin poisoning in mice. Toxicon 33(9):1231-1237