Biotechnology and Bioinformatics (1+1)

5.1.11. Marine Toxins

A toxin is a substance possessing a specific functional group arranged in the molecule (s) and showing strong physiological activity. A toxin has the potential to be applied as a drug or pharmacological reagent. Furthermore, even if direct use as a drug is not feasible because of potent of harmful side effects, the toxin can serve as a model for synthesis or improvement of other drugs. Many attempts have been made to develop useful drugs from the sea by screening for anticarcinogenic, antibiotic , growth-promoting (or inhibiting), hemolytic, analgetic, antispasmodic, hypotensive, and hypertensive agents. Marine toxins show great promise not only as pharmacological reagents, but also as models for the development of new synthetic chemicals.

• Tetrodotoxin, the main action of which is paralysis of peripheral nerves, is a valuable pharmacological reagent. Because it inhibits specifically the sodium permeability of nerve membranes, it has been valuable for elucidating the excitation mechanism.
• Insecticide developed from nereistoxin are widely marketed. Fishermen are familiar with the fact that flies die when they come into contact with the dead marine annelid, Lumbrinereis (Lumbriconereis) brevicirra, commonly used as bait. A new insecticide was developed from nereistoxin that was active against the rice stem borer and other insect pests, it does not appear to be toxic to warm blooded animals, and resistant strain s of insects do not readily develop.
• Recently ciguatoxin, palytoxin and halitoxin have also been investigated and provide interesting new information.
• Ciguatera is a human disease caused by the ingestion of a wide variety of coral reef fishes that contain toxins accumulated via the marine food web. The principal toxin of ciguatera poisoning is a heat-stable, lipid-soluble compound named ciguatoxin. Origin of the toxin is not yet fully understood but may be derived by the fish from ingestion of toxic tropical red tide dinoflagellates such as Pyrodinium bahamense.
• Halitoxin, a toxic complex of several marine sponges of the genus Haliclona, has been isolated, partially purified, spectrally characterized, and chemically degraded, yielding a proposed chemical structure for the toxin. The toxin has proved to be a complex mixture of high molecular weight and toxic pyridinium salts, and can be isolated from the sponges, Haliclona rubens, H. viridis, and H. erina. The sponge extracts are toxic for fish and mice.
• Lophotoxin , a new neuromuscular toxin isolated from several Pacific gorgonians of the genus Lophogorgia, has been isolated and purified. Originally discovered during a search for chemical defense adaptations of marine organisms, a variety of horny corals or gorgonians (sea fans and whips) in tropical or subtropical waters were studied; and cytotoxic , ichthyotoxic and antibacterial activity was noted. Lophotoxin inhibits nerve-stimulated contraction without affecting contraction evoked by direct electrical stimulation of the muscle. The data suggest that epoxylactone and furanoaldehyde groups may be responsible for the potent biological properties of lophotoxin.
• Palytoxin , an extremely poisonous, water-soluble substance from marine coelenterates belonging to the genus Palythoa. Palytoxin influences calcium and potassium ion transport in nerves and the heart. Animals undergo paralysis and heart failure. Palytoxin is synthesized by a marine Vibrio sp. growing symbiotically with the coelenterate Palythoa and apparently related to Vibrio cholerae. Toxins from marine animals that are well known have been summarized and are listed in Table 1.

Several marine organisms have provided useful drugs : liver oil from some fish provides excellent sources of vitamins A and D; insulin has been extracted from whales and tuna fish; and the red alga, Digenia simplex, has long been used as an anthelminthic.

Table 1. Marine Toxins

Toxin	Source	Dose and Route	Mechanism of action	Comment
Cephalotoxin	Octopus vulgaris	150-300mg subcutaneous (in the dog)	Lowers blood pressure, arrests heart and respiration; neurotoxicologically similar to saxitoxin, tetrodotoxin	Human deaths have occurred from octopus bites
Ciguatoxin	Coral reef organisms		Neurotoxic effects; nausea, vomiting, diarrhea; recovery after several weeks	Occurs in moray eel, barracuda, several fish species off Ryukyu Islands
Halitoxin	Haliclona viridis	270mg interperitoneal (in the mouse)	Blocks nerve-muscle junction; effective against cancer cells
Holotoxin	Holothuria tubulosa	5-15mg intravenous (mouse)	Cardiotoxic	A toxin of the sea cucumber
Nereistoxin	Lumbriconereis heteropoda	33 mg intravenous (mouse)	Causes muscle paralysis, halts respiration	Used as an insecticide in Japan
Palytoxin	Palythoa spp.	100µg intraperitoneal (mouse)	Constricts coronary artery	Effect in man occurs upon ingestion of the file fish
Saxitoxin,	Saxidomus giganteus	10µg intraperitoneal (mouse)	Causes neuromuscular junction paralysis	Effect in man occurs upon ingestion of clams and muscles.
Tetrodotoxin	Puffer fish	8-20µg gastrointestinal (mouse)	Neurotoxic; causes respiratory paralysis	Used in clinical trials for pain in neurogenic leprosy