Saxitoxins toxicity

Saxitoxin acts quickly, and can kill an individual within a few minutes of inhalation of a lethal dose. It acts by directly blocking nerve conduction, and causes death by paralyzing muscles of respiration. At slightly less than the lethal dose, the victim may not experience any effects at aU. Botulinum toxin needs to invade nerve terminals in order to block the release of neurotransmitters, which under normal conditions control muscle contraction. The symptoms from botulinum toxin are slow to develop (from hours to days), but are just as lethal, causing respiratory failure. This toxin blocks biochemical action in the nerves, which activate the muscles necessary for respiration, which leads to snffocation. Unlike saxitoxin, toxicity for botulinum is greater through ingestion than inhalation. 

Saxitoxin (STX) is a toxin which is found in marine microorganisms. It is most likely synthesized by bacteria which live in symbiosis with dinoflagellates, a component of phytoplankton. Through the marine food chain, it can lead to poisoning of humans. The mechanism of toxicity of saxitoxin is vety similar to that of tetrodotoxin. Saxitoxin binds from the outside of the membrane to various forms of voltage-sensitive Na+channels and blocks the channel in an activation state-independent manner. 

The saxitoxins accumulated from the plankton by molluscan filter-feeders can be passed on to other animals. Gastropods such as whelks, which prey on bivalves, have been found to be toxic, apparently from consuming toxic bivalves (65). Such... 

Of the various chemical assays that have been developed for the saxitoxins (75,76), that described by Bates and Rapoport, based on the oxidation of saxitoxin to a fluorescent derivative, has proved to be the most useful. Other assay methods have been developed from it (77-79). The Bates and Rapoport method is virtually insensitive to the N-l-hydroxyl saxitoxins as originally described and so, like the presently available immunoassays, fails as a general assay for either concentration or toxicity. However, it is quite sensitive for those toxins it does detect and has been the basis for other useful methods. 

Some Chemical Considerations Relevant to the Mouse Bioassay. Net toxicity, determined by mouse bioassay, has served as a traditional measure of toxin quantity and, despite the development of HPLC and other detection methods for the saxi-toxins, continues to be used. In this assay, as in most others, the molar specific potencies of the various saxitoxins differ, thus, net toxicity of a toxin sample with an undefined mixture of the saxitoxins can provide only a rough approximation of the net molar concentration. Still, to the extent that limits can be placed on variation in toxin composition, the mouse assay can in principle provide useful data on trends in net toxin concentration. However, the somewhat protean chemistry of the saxitoxins makes it difficult to define conditions under which the composition of a mixture of toxins will remain constant thus, attaining a reproducible level of mouse bioassay toxicity is difficult. It is therefore useful to review briefly some of the chemical factors that should be considered when employing the mouse bioassay for the saxitoxins or when interpreting results. Similar concepts will apply to other assays. 

Two factors will be discussed here 11-hydroxysulfate epimerization and sulfa-mate hydrolysis. Other transformations, mediated by shellfish or bacteria, are possible and the saxitoxins are also subject to gross decomposition, resulting in non toxic products. These factors will complicate the picture slightly, but not alter the basic point. 

The susceptibility of the sulfamates to hydrolysis is intermediate with respect to procedures commonly used for extraction and manipulation of extracts. Quantitative hydrolysis of the pure sulfamate toxins can be accomplished (9) by heating at 100 C for 5 min in the presence of not less than 0.1 M free acid (pH 1 or below). Milder conditions appear insufficient (10). Figure 9 summarizes results from two separate experiments in which samples of nontoxic clam flesh, enriched with constant amounts of saxitoxin Cl (4), were acidified to differing final concentrations of HCl and heated for 5 min at 100 C. The difference between 0.1 M HCl, which would be sufficient for hydrolysis of the pure toxin, and the HCl concentration required to attain plateau toxicity, probably reflects the buffer capacity of... 

In other chapters of this volume considerable attention is given to marine toxins whose cellular sites of action have been identified. For example, saxitoxin, brevetoxin, and sea anemone toxins are prototypes of toxic molecules whose chemical structure is known, and whose actions on ionic channels in the cell membrane have been elucidated. Recent additions to such toxins are the piscivorus cone... 

Agelasine, 320 Aiptasia pallida, 304,310 Aiptasia species, toxic protein, 321 Aiptasiolysin, 304,310 Alexandrium dinoflagellates clones, 36,38-3 saxitoxin source, 21 toxicity, 36... 

Saxitoxin is a small tricyclic structure isolated from oceanic red tides it has attracted much interest for its peculiar structure and toxicity as a paralytic agent. The core structure that is related to a l-iminooctahydropyrrolo[l,2-f]-pyrimidine nucleus was prepared by rearrangement after oxidation of a double bond contained in a medium-size guanidine ring. This key intermediate in the synthesis was prepared from azide 376 with a judicious use of Mbs... 

Neurotoxins, such as saxitoxin and anatoxin-a, have been implicated in mediating competitive interactions between toxic cyanobacteria and other photoautotrophs, but few studies have explicitly examined the allelopathic effects of these compounds (e g., Kearns and Hunter 2001). Although it is reasonable to assume that these compounds bind to algal and cyanobacterial sodium channels in a similar fashion as in vertebrate neurons, support for this hypothesis is currently lacking. 

The amount of total PSP toxins equivalent in toxicity to 0.8 ppm saxitoxin. 

Cyanobacteria toxins are toxins produced by certain species of blue-green algae that have become a major environmental and public health concern. The behavior of cyanotoxins during chlorination treatment has been recently reviewed by Merel et al. [129]. Chlorination DBFs have been reported only for the hepatotoxins microcystin-LR and cylindrospermopsin. Other cyanotoxins, such as nodularins, saxitoxins, and anatoxins, have yet to be investigated. Different isomers of six chlorination products of microcystin-LR have been characterized dihydroxy-microcystin, monochloro-microcystin, monochloro-hydroxy-microcystin, monochloro-dihydroxy-microcystin, dichloro-dihydroxy-microcystin, and trichloro-hydroxy-microcystin. Only two chlorination DBFs have been reported so far for cylindrospermopsin 5-chloro-cylindros-permopsin and cylindrospermopsic acid [129]. Chlorination of microcystin, cylindrospermopsin, and nodularins seems to reduce the mixture toxicity however, this aspect has not been extensively studied [129]. 

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