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Tetrodotoxin produced by Pufferfish By Charles Brown Biochemistry •Binds to site 1 of the fast voltage gated sodium channel •It blocks the Na+ current in human hearts and prevents contraction Tetrodotoxin •Potent neurotoxin • Named after fish Teratodoniformes = “four toothed” •Blocks Na+ channels on surface of nerve membranes •Found in more than just puffer fish Production of TTX The pufferfish does not create the poison itself; rather it is generated by various genera of bacteria within the fish. The fish obtains the bacteria by eating food containing these bacteria. Pufferfish that are born and grown in captivity do not produce tetrodotoxin until they receive some of the poison-producing bacteria. Natural Defenses Puffers use a combination of pectoral, dorsal, anal, and caudal fins for propulsion that make them highly maneuverable but very slow, and therefore comparatively easy targets for predators. As a defense mechanism, puffers have the ability to inflate rapidly, filling their extremely elastic stomachs with water. Thus, a hungry predator stalking the puffers may suddenly find itself facing what seems to be a much larger fish and pause, giving the puffers an opportunity to retreat to safety. Poison •Extremely Potent •1 milligram is lethal to an adult human •LD50 for the mouse is 10 nanograms •100 times more lethal than black widow • 10,000 times more lethal than cyanide Poison • Stages of poisoning 1. Numbness of the lips and tongue • numbness in the face and extremities • sensations of lightness or floating 2. Increasing paralysis • Some victims are unable to move, sitting may be difficult. • Increasing respiratory distress • Speech is affected 3. Death usually occurs within 4 to 6 hours • Due to respiratory paralysis Treatment Provide prehospital care with careful attention to the airway. Patients may require endotracheal intubation for oxygenation and airway protection in the setting of muscle weakness and respiratory failure, which can occur soon after ingestion of the tetrodotoxin. Cardiac dysfunction may require IV intervention with fluids, pressors, and antiarrhythmics. Severely poisoned patients may be very weak, have difficulty speaking, and be unable to provide a history. Thus, clues from the environment and bystanders are very important. Drugs •No drug has been shown to reverse the effects of tetrodotoxin poisoning. Treatment is symptomatic. Specific drug efficacy has only been documented anecdotally. •Anticholinesterase drugs (eg, neostigmine) have been proposed as a treatment option but have not been tested adequately. Tetrodotoxin History •Bacteriological/ Endosymbiotic • Farmed Puffer fish do not produce TTX unless they are fed fed tissues of TTX producing fish •Bacteria produce TTX for the Octopus •Xanthid crabs contain TTX and paralytic shellfish toxin •Puffer fish are immune to TTX due to mutation in Na+ channel receptors Other TTX uses •Anesthetics in Animals •Prevention of damage to brain following stroke •Suppressing pain in cancer patients •Relieving the symptoms of withdrawal in opiate addicts Pufferfish Pufferfish are considered one of the most advanced group of bony fish. Pufferfish have few bones, because most of their bones in their head and body, through time, have fused together Pufferfish skin is thick and feels leathery and is covered by scales that have been modified into spines. Distribution The entire Tetraodontidae family has a worldwide distribution. Its members are found near-shore in shallow seas from the Atlantic to the Pacific. Many members of the family can be found in areas of brackish water such as estuaries. Some select species are known to exist entirely in freshwater. Breeding Spawning can take place at any time during a day, year-round. One-year old fish are already in the reproductive age. Average fecundity—3000 eggs, maximum— about 6000. What does a Pufferfish eat? A variety of small crustaceans. Small fish Sponges Sea Urchins Owners of puffer fish in tropical aquariums report that their pets can be quite greedy, and seem to eat anything! How Prepared/Ingested The first symptoms occur 15 minutes to several hours postingestion of tetrodotoxin-containing food. A recent report on toxicity found that initial symptoms may occur up to 20 hours after ingestion. How Prepared/Ingested Only specially licensed chefs can prepare and sell fugu to the public. The consumption of the liver and ovaries is forbidden. Small amounts of the poison give a special desired sensation on the tongue, these parts are considered the most delicious by some gourmets. Every year a number of people die because they underestimate the amount of poison in the consumed fish parts. Statistics In the US: Reports of tetrodotoxin poisoning are rare in the US, but a 1996 report in the Morbidity and Mortality Weekly Report (MMWR) documents 3 cases of tetrodotoxin toxicity from persons ingesting contaminated fugu imported by a coworker from Japan. Internationally: Despite the careful training and certification of fugu chefs in Japan, cases of mortality and morbidity from puffer fish ingestion continue to be reported. Estimates vary, but up to 50 deaths may occur each year from tetrodotoxin poisoning in Japan. Trivia Dolphins have been observed using puffers as a sort of toy in the wild. They tease the puffers with their teeth, causing the small fish to become alarmed and then inflate. When lifted out of water, puffers can inflate with air, but they may have problems deflating again afterwards. When this happens with aquarium specimens, fishkeepers hold the puffer underwater by the tail, head upwards, and shake the fish gently until the air escapes out of the mouth. References Froese, R. and D. Pauly. Editors.. 448 Family Tetraodontidae Puffers. FishBase. Retrieved on 2007-02-10 Arreola, V.I., and M.W. Westneat. 1996. Mechanics of propulsion by multiple fins: kinematics of aquatic locomotion in the burrfish (Chilomycterus schoepfi). Proceedings of the Royal Society of London B 263: 1689–1696. Ebert, Klaus (2001): The Puffers of Fresh and Brackish Water, Aqualog, ISBN 393170260X. Gordon, M.S., Plaut, I., and D. Kim. 1996. How puffers (Teleostei: Tetraodontidae) swim. Journal of Fish Biology 49: 319–328. Plaut, I. and T. Chen. 2003. How small puffers (Teleostei: Tetraodontidae) swim. Ichthyological Research 50: 149–153.