Okadaic acid, diarrhetic shellfish poisoning caused

In addition to okadaic acid, dinophysistoxin-1 (i.e., 35-methylokadaic acid), 7-0-palmitoyl-okadaic acid, and pectenotoxin 2 are reported to be diarrhetic toxins from shellfish 34). Application of 1 xg of dinophysistoxin-1 to mouse ear caused as strong irritation as the same dose of okadaic acid. Interestingly, the potencies of these compounds in the irritant test on mouse ear correlated well with their potencies as diarrhetic shellfish poisons. Dinophysistoxin-1 induced ODC activity as strongly as okadaic acid. Recently, we found that dinophysistoxin-1 is also a new non-TPA type tumor promoter with as high activity as okadaic acid 35). 

Additionally, a number of marine toxins with medical and toxicological importance have been isolated from marine flora and fauna. Okadaic acid, Fig. (62) is the main toxin produced by dinoflagellates, which can accumulate in the hepatopancreas of mussels and caused diarrhetic shellfish poisoning in consumers [505,506], However, this toxin is also a tumor promoter and a specific potent inhibitor of protein phosphatases which may provokes mitotic arrest and apoptosis of leukemia cells [507-509], These types of compounds have been reported in shellfish and phytoplankton, and more recently, in Spanish mussels [510], Portuguese bivalves [511], and the diatom Thalassiosira weissflogii [512],... 

Ishige, M., Satoh, N., andYasumoto, T. 1988. Pathological studies on mice administered with the causative agent of diarrhetic shellfish poisoning (okadaic acid and pectenotoxin-2). Hokkaidoritsu Eisei Kenkyushoho 15-18. 

Kumagai, M., Yanagi, T, Murata, M., Yasumoto, T, Kat, M., Lassus, P, and Rodriguez-Vazquez, A., 1986. Identification of okadaic acid as the causative toxin of diarrhetic shellfish poisoning in Europe. Agric Biol Chem 50, 2853—2857. 

The sponge Halichondria okadai contains a polyether metabohte named okadaic acid (16) that was also isolated as a causative agent of diarrhetic shellfish poisoning (DSP) from mussels and other bivalves (14). However, the real producers are dinoflagellates of the genus Dinophysis. It is a potent cancer promoter that was found to be caused by inhibition of protein phosphatases 1 and 2A at nanomolar levels. Pectenotoxins are also involved in DSP and are produced by Dinophysis spp. pectenotoxin 2 (17) inhibits actin polymerization (14). 

Because the pectenotoxins occur in association with okadaic acid and the dinophysistoxins, they were classified within the diarrhetic shellfish poison group [62], However, most available information now indicates that these compounds do not cause diarrhea in experimental animals. No diarrhoea was seen in mice receiving pure PTX-2, PTX-11, or PTX-2 seco acids. It was shown, however, that the Cg-diol ester of okadaic acid is co-extracted with the pectenotoxins, so that without careful purification, contamination of the latter with diarrhetic substances is likely [26]. 

B. Diarrhetic shellfish poisoning is caused by several identified toxins, all of which appear to be produced by marine dinoflagellates. Suspected toxins include okadaic acid, dinophysistoxins, and azaspiracid. 

Phycotoxins, also named shellfish toxins, are produced by free-living micro-algae upon which the shellfish feed. The toxins are concentrated in the shellfish, which act as a vector transferring the toxic compounds to the food chain. Control of the presence of these toxins in food is required as they can cause neurotoxic, diarrhetic, paralytic, or amnesic poisoning. LC methods with fluorescence detection are now available for the determination of some of these compounds, such as domoic acid, saxitoxins, okadaic acid, and ciguatoxins. Also, an enzyme inhibition assay has been described for the determination of okadaic acid in mussels using fluorescent endpoint detection. 

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