Neurotoxic Shellfish Poisoning

This chapter deals with single crystal x-ray diffraction as a tool to study marine natural product structures. A brief introduction to the technique is given, and the structure determination of PbTX-1 (brevetoxin A), the most potent of the neurotoxic shellfish poisons produced by Ptychodiscus brevis in the Gulf of Mexico, is presented as an example. The absolute configuration of the brevetoxins is established via the single crystal x-ray diffraction analysis of a chiral 1,2-dioxolane derivative of PbTX-2 (brevetoxin B). 

The toxicological consequences of P. brevis red tides are mass mortality of fishes exposed to the red tide toxic shellfish which, if consumed, result in human neurotoxic shellfish poisoning and an irritating aerosol which results from contact with P. brevis cell particles entrapped in seaspray. In all cases, the threshhold levels for intoxication are in the picomolar to nanomolar concentration ranges, implying a specific locus or loci of action for brevetoxins (reviewed in 6). 

Some dinoflagellates of the genus Alexandrium produce neurotoxic compounds known as paralytic shellfish poisoning (PSP) toxins. Because these toxins can contaminate filter-feeding shellfish they may threaten public health and create economic problems for fisheries. PSP-toxins include at least a dozen saxitoxins, neosaxitoxins, and gonyautoxins (Scheme 1). 

Ishida, H., et al.. Study on neurotoxic shellfish poisoning involving oyster, Crassostrea gigas, in New Zealand, Toxicon, 34, 9, 1050, 1996. 

Morris, P.D., et al.. Clinical and epidemiological features of neurotoxic shellfish poisoning in North Carolina, Am. J. Public Health, 81, 4, 471, 1991. 

Nozawa, A., Tsuji, K. and Ishida, H., Implication of brevetoxin B1 and PbTx-3 in neurotoxic shellfish poisoning in New Zealand by isolation and quantitative determination with liquid chromatography-tandem mass spectrometry, Toxicon, 42, 1, 91, 2003. 

Paralytic shellfish poison, like botulinum toxin, is a neurotoxic substance and can also affect certain muscles, including the heart, which are under nervous system control. Some poisoned humans who have recovered from the effects of PSP have described the early stages of intoxication as not at all unpleasant a tingling sensation in the lips and face and a feeling of calm. Those who die from PSP ingestion do so because of respiratory failure. 

The neurotoxins may be transmitted to man through bioaccumulation in an intermediate marine host. Toxic bivalves result from the filter-feeding of jP. brevis cells during red tides, and if consumed result in neurotoxic shellfish poisoning, or NSP. Human oral intoxication is rarely fatal. 

Earlier research had already suggested that certain blooms Aph. flos-aquae could produce paralytic shellfish poisons. These studies used water blooms collected from Kezar Lake, New Hampshire (25,30). In 1980 Carmichael isolated a neurotoxic strain of Aph. flos-aquae from a small pond in New Hampshire. These strains have also been shown to produce toxins similar to saxitoxin and neo- axitoxin (23) and are the ones used in the studies presented here. 

Neurotoxic Shellfish Poisoning (NSP) is caused by a red-tide producer that was first identified in 1880 from Florida, with earlier historical references. It causes sickness in humans lasting several days. NSP is not fatal to humans however, it is known to kill fish, invertebrates, seabirds, and marine mammals (e.g., manatees). It is caused by the brevetoxin family (brevetoxin + 10 related compounds produced by the dinoflagellate Karenia brevis a.k.a. Gymnodinium breve. The main contamination problems include oysters, clams, and other filter feeders of the Gulf of Mexico and southeast Atlantic, including North Carolina. 

After the 1992-93 outbreak of neurotoxic shellfish poisoning (NSP) in New Zealand, several metabolites of brevetoxins were isolated from seafood . NSP is a term applied to an illness resulting from the ingestion of shellfish exposed to blooms of dinoflagellate K. brevis < 1965MI111, 1991MI471>. 

Symptoms of Brevetoxins Poisoning Human Exposure to Neurotoxic Shellfish Poisoning... 

Ishida, H., Nozawa, A., Nukaya, H., Rhodes, L., McNabb, P, Holland, PT, Tsuji, K. 2004a. Confirmation of brevetoxin metabolism in cockle, Austrovenus stutchburyi, and greenshell mussel, Perna canaliculus, associated with New Zealand neurotoxic shellfish poisoning, by controlled exposure to Karenia brevis culture. Toxicon 43, 701-712. 

Morohashi, A., Satake, M., Naoki, H., Kasper, H.F., Oshima, Y, Yasumoto, T. 1999. Brevetoxin B4 isolated from greenshell mussels Pema canaliculus, the major toxin involved in neurotoxic shellfish poisoning in New Zealand. Natural Toxins 7, 45 8. 

Poli, M.A., Musser, S.M., Dickey, R.W., Eilers, P.P., and Hall, S. 2000. Neurotoxic shellfish poisoning and brevetoxin metabolites a case study from Elorida. Toxicon 38, 981-993. 

Novelli, A, Femandez-Sanchez, M.T., Kispert, J., Torreblanca, A, Gascon, S., and Zitko, V 1992a. The amnesic shellfish poison domoic acid enhances neurotoxicity hy excitatory amino acids in cultured neurons. Amino Acids 2,233-244. 

Peng, Y.G., Taylor, T.B., Finch, R.E., Switzer, R.C., and Ramsdell, J.S. 1994. Neuroexcitatory and neurotoxic actions of the amnesic shellfish poison, domoic acid. NeuroReport 5, 981-985. 

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