Toxicants, natural domoic acid

Truelove, J., Mueller, R., Pulido, O., Martin, L., Femie, S., and Iverson, F. 1997. 30-day oral toxicity study of domoic acid in cynomolgus monkeys lack of overt toxicity at doses approaching the acute toxic dose. Natural Toxins 5, 111-114. 

In 1987, the first confirmed case of a naturally occurring neurotoxic diatom bloom was reported in Prince Edward Island, Canada, later confirmed to be caused by the production of domoic acid from the pennate diatom Nitzschia pungens, now renamed Pseudo-nitzschia multiseries (Bates et ah, 1989 Subba Rao et ah, 1988). Since this first outbreak, many (but not aU) species of Pseudo-nitzschia have been confirmed to produce domoic acid (as well as some species of Amphora and now Nitzschia (Kotaki et ah, 2000) see Bates, 1998, 2000, for a summary). These potentially toxic species include P. multiseries, P. pseudodelicatissima, P. delicatissima, P. seratia, P. australis, P. pungens, and P.fraudulenta, although it is apparent that not aU species are toxic in aU locations, nor are individual strains toxic under aU conditions. 

Potent excitatory effects, parent of a family of toxic natural kainoids present in fungi. Domoic acid, which has trans, traws-CHMe-CH=CH-CH=CH—CHMeC02H in place of the isopropenyl side-chain of kainic acid, is extraordinarily toxic, with fatalities ensuing through eating contaminated shellfish (Baldwin et at, 1990). 

So it appears that domoic acid has been with us for some time and will continue to represent a global health threat in the future. To both understand the nature of DOM toxicity, as well as to develop potentially useful therapeutic strategies for dealing with DOM intoxication, it is necessary to understand how this compound produces its effects on the mammalian nervous system. This is the subject of the next section. 

In summary, therefore, there are a variety of ways in which domoic acid appears to produce neuronal toxicity, but aU involve either direct or indirect "over-stimulation" of post-s)maptic receptors leading to the influx of excessive amounts of Ca. The differential sensitivity of different neuronal populations in different regions of the brain, is probably determined both by which of these mechanisms is present, as well as by how many of them are actively involved at the time of toxic insult. Let us now consider the nature of the toxicity produced by DOM, and learn why it s something you want to avoid. 

Before describing mammalian toxicity it is fitting to mention the natural vehicle for DOM in our food chain the lowly bivalve (see the next section). There is absolutely no evidence that even massive doses of domoic acid (1000 ppm) produce any toxicity in mussels, clams or oysters. In contrast, the humans admitted to intensive care imits in 1987 appear to have consumed less than 4.0 mg/kg of domoic acid (4 ppm). It is not known at this time whether bivalves lack the proper forms of glutamate receptors or whether they simply have no capacity to absorb the toxin from their digestive gland, but in either case they appear to have a distinct advantage over us. 

Structure, nomenclature and occurrence ASP is a less common type of poisoning. It occurs after ingestion of shellfish contaminated by a specific toxic amino acid referred to as domoic acid (10-247), a naturally occurring neuroexcitatory toxin produced primarily by the marine diatom Pseudonitzschia multiseries, which is widespread... 

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