SAXITOXIN

Description

First recognized in 1957 by Shantz et al. in the butter clam Saxidomus giganteus, saxitoxin is a naturally occurring toxin that is synthesized by various marine dinoflagellates and cyanobacteria. It is used in neurochemical and molecular biology research, but regulatory concerns have focused on its weaponization and potent toxicological effects on animals and humans. Saxitoxin causes paralytic shellfish poisoning (PSP) in humans and other animals; whales having ingested organisms contaminated with the toxin have died just hours after exposure. In humans, PSP can occur as a result of consuming shellfish or other seafood in which saxitoxin has accumulated. While effects have been documented worldwide, the sources of contaminated seafood have been identified as primarily the west and east coasts of the United States.
To date, more than 30 different saxitoxin analogs have been identified. These include pure saxitoxin (STX), neosaxitoxin (neoSTX), the gonyautoxins (GTX), and decarbamoylsaxitoxin (dc-STX); of these, STX, 6NeoSTX, GTX1, and dc-STX seem to be the most toxic. The term saxitoxin typically refers to this collection of compounds produced naturally by cyanobacteria.
Saxitoxin is far more potent than the classic puffer fish toxin tetrodotoxin, and is one of only two naturally occurring Schedule 1 chemical warfare agents (the other is ricin). In 1970, President Nixon ordered stocks of the toxin destroyed in compliance with U.N. agreements on biological weapons; however, the Central Intelligence Agency revealed in 1975 that there was a remaining supply, which was distributed to research facilities by the National Institutes of Health in order to study neurological diseases.

Description

Saxitoxin is a pyrrolopurine alkaloid and potent neurotoxin found in a variety of shellfish, including mussels, clams, and scallops. It is produced by marine dinoflagellates (e.g., Gonyaulax catenella and Alexandrium tamarense), freshwater cyanobacteria (e.g., Dolichospermum cicinale), and other microorganisms that the shellfish ingest. The term saxitoxin is also used for a series of structurally related microbe-derived neurotoxins.
Saxitoxin takes its name from the Alaskan butter clam (Saxidomus gigantea) from which it was first identified in 1937 by Hermann Sommer1 and co-workers at the University of California, San Francisco. In 1966, Edward J. Schantz1 and colleagues at the US Army Biological Laboratories (Fort Detrick, MD) purified saxitoxin and determined its properties. By 1975, Schantz was at the University of Wisconsin (Madison); he and collaborators there and at Iowa State University (Ames) elucidated the structure of saxitoxin.
In 2008, Mark A. Simmons at Northeast Ohio Medical University (Rootstown) wrote:
Saxitoxin (STX), a highly selective and potent blocker of voltage-dependent sodium channels in motor nerves, causes skeletal muscle paralysis. It is found in filter-feeding mollusks [that] consume planktonic algae. . . . Ingestion of these mollusks by humans results in paralytic shellfish poisoning, which may result in death in a matter of hours if sufficient toxin is absorbed. There is no antidote for STX poisoning.
Also in 2008, Brian A. Neilan and co-workers at the University of New South Wales (Sydney) proposed a 10-step biosynthetic pathway to saxitoxin in the freshwater cyanobacterium Cylindrospermopsis raciborskii. For much more information about saxitoxin, see the ScienceDirect information page.
1. Sommer and Schantz were pioneers in characterizing shellfish toxins.

Chemical properties

Crystalline solid; soluble in water and me thanol; forms dihydrochloride with HCl.

The Uses of SAXITOXIN

Saxitoxin is an alkaloid of nonplant origin.It is the neurotoxic constituent of dinoflagel lates (Gonyaulax catenella and G. excavata)the so-called “red tide” found along the U.S.coast. Shellfish, clams, and scallops consumethis and become extremely poisonous forhuman consumption.

The Uses of SAXITOXIN

Mussel poison; clam poison; paralytic shellfish poison; gonyaulax toxin. These poisonous shellfish have been connected to instances of toxic”red-tides” where the high concentration of algae discoloring the water were of the Gonyaulax genus. Used as a too

The Uses of SAXITOXIN

As a Schedule 1 controlled substance under the Chemical Weapons Convention of 1993, the use of saxitoxin is extremely limited outside of weaponized forms. Its use as a chemical reagent in research is its other important use, as it has been instrumental in experiments to elucidate the mechanisms involved in sodium channels used in cellular communication.

Definition

ChEBI: An alkaloid isolated from the marine dinoflagellates and cyanobacteria that causes paralytic shellfish poisoning.

Health Hazard

Saxitoxin is an extremely toxic substance.It binds to sodium channels and the blocksnerve membrane. In humans, ingestion ofthis compound can produce tingling andburning in the lip, tongue, face, and thewhole body within an hour. This is fol lowed by numbness, muscular incoordina tion, confusion, headache, and respiratoryfailure. Death may occur within 12 hours.
LD50 value intraperitoneal (mice): 0.005mg/kg
LD50 value oral (mice): 0.26 mg/kg
Intravenous administration of 1 mL of1:2000 solution of prostigmine methylsulfatehas been reported to be effective againstsaxitoxin poisoning (Hodgson et al. 1988).

Environmental Fate

Dinoflagellates (flagellate protists, plankton) are primarily responsible for the biosynthesis of saxitoxin, and bioaccumulation tends to occur in several shellfish such as mussels, clams, scallops, and cockles. Broth made from shellfish can harbor saxitoxin as well due to its stability at normal cooking temperatures. Consumption of the shellfish leads to toxicity in humans, while consumption of other organisms in which saxitoxin has accumulated (up the food chain, for example) has historically affected other animals such as whales.
Data describing the environmental fate of saxitoxin is extremely limited. There have been some studies investigating the absorption/desorption capacities of various soils for the compound, but more exhaustive studies are yet to be reported.

Toxicity evaluation

Saxitoxin interrupts nerve transmissions by binding to voltagegated sodium channels. Positively charged guanidinium groups of saxitoxin interact with negatively charged carboxyl groups at a site on the sodium channel (in a one-to-one ratio) of neurons and muscle cells, resulting in blocked action potentials and interrupted transmissions. The inactivation of vasomotor nerves along with vascular smooth-muscle relaxation follows and hypotension can additionally occur. When muscles in the respiratory or cardiovascular system are affected, death can result.
Intraperitoneal inoculation with STX extract in the freshwater fish Hoplias malabaricus resulted in a variety of systemic effects culminating in oxidative stress observed in the brain, leading to lipid, protein, and DNA damage. Although the exposure in this study was subchronic, apoptotic cellular processes were implicated.

References

Schantz et al., J. Arner. Chern. Soc., 97, 1238 (1975)