Diarrhetic toxins

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). 

Ramstad, H., Hovgaard, E, Yasumoto, T, Larsen, S., andAune,T. 2001. Monthly variations in diarrhetic toxins and yessotoxin in shellfish from coast to the inner part of the Sogneljord, Norway. Toxicon 39, 1035-1043. 

Since the early Japanese studies on DSP, the toxins in mussels and scallops were suspected to be different. The main diarrhetic toxin found in scallops was found to be a mixture of 7-(9-acylderivatives of dinophysistoxin-1 (DTX-1), ranging from tetradecanoic acid (C14 0) to docosahexaenoic acid (C22 6to3), and designated as dinophysistoxin-3 (DTX-3) (Yasumoto et al. 1985). These acylated forms have never been found in marine microalgae, and so it was presumed that they originated in the bivalve by acylation (Lee et al. 1989). Direct evidence of this biotransformation by shellfish was obtained by artificially feeding scallops with D. forth collected from the sea (Suzuki et al. 1999). 

James, K.X, Carmody, E.P., Gillman, M., Kelly, S.S., Draisci, R., Lucentini, L., and Giannetti, L. 1997b. Identification of a new diarrhetic toxin in shellfish using liquid chromatography with fluorometric and mass spectromefiic detection. Toxicon >5 6), 973-978. 

Puech, L., Dragacci, S., Gleizes, E., and Fremy J-M. (1999) Use of immunoaffinity columns for clean-up of diarrhetic toxins (okadaic acid and dinophysistoxins) extracts from shellfish prior to their analysis by HPLC/fluorimetry. Food Additives and Contaminants, 16, 6, 239-251. 

Masselin, R, Lassus, R, and Bardouil, M., High performance liquid chromatography analysis of diarrhetic toxins in Dinophysis spp. from the Erench coasf J. Appl. PhycoL, 4, 385, 1992. 

Figure 5.59 Molecular structures of the diarrhetic shellfish poisons (a) pectenotoxin-6 (PTX6) (b) okadaic acid (OA) (c) dinophysistoxin-1 (DTXl) (d) yessotoxin (YTX). Reprinted from J. Chromatogr., A, 943, Matrix effect and correction by standard addition in quantitative liquid chromatographic-mass spectrometric analysis of diarrhetic shellfish poisoning toxins , Ito, S. and Tsukada, K., 39-46, Copyright (2002), with permission from Elsevier Science.

Three classes of polyethers, okadaic acid derivatives, pectenotoxins, and yessotoxin were isolated from bivalves in connection with diarrhetic shellfish poisoning. The etiology of the toxins, toxicological properties, and determination methods are described. 

Diarrhetic shellfish poisoning is an illness caused by polyether toxins produced by dinoflagellates and accumulated in shellfish (31). Patients suffer from diarrhea, nausea, and stomach pain but recover within three days without serious aftereffects. Despite the relatively mild symptoms, careful attention should be paid to the... 

Figure 6. Fluorometric HPLC of diarrhetic shellfish toxins A, AM (9-anthrylmethyl) esters of constituents which have a carboxylic acid column, Develosil ODS (Nomura Chem.) solvents, CH3CN-CH3OH-H2O (8 1 1) monitor ex. 365, em. 412 nm and B, AN (anthroyl) esters of PTXl and PTX4 column and solvents were the same as those in A monitor x. 365, em. 465.

The toxins responsible for DSP include a series of polyether molecules (including okadaic acid and six derivatives of dinophysistoxin), four pecteno-toxins (polyether lactones), and yessotoxins (including two sulfate esters that resemble brevetoxins) (Murata, 1982 Murata, 1987 Tachibana et al., 1981 Yasumoto, 1989). Diarrhetic shellfish poisons are produced primarily by dinoflagellates from the genera Dinophysis, although Prorocentrum lima also produces both okadaic acid and dinophysistoxin-1 (Heredia-Tapia et al., 2002). 

The biological activities of the other diarrhetic shellfish poisons are not well understood, and some of the toxins included in the DSP complex may not be... 

AZP, the most-recently characterized marine seafood poisoning, is associated with eating shellfish contaminated with azaspiracids. The first human intoxications attributed to AZP occurred in the Netherlands, and the symptoms included those similar to DSP (i.e., nausea, vomiting, severe diarrhea, and stomach cramps). However, although chemical analyses did not identify significant levels of the diarrhetic shellfish poisons, they identified a new class of toxins (James et ah, 2003a). 

Aune, T. and Yndestad, M., Diarrhetic shellfish poisoning, in Falconer, I.R., ed.. Algal Toxins in Seafood and Drinking Water, Academic Press, San Diego, 1993. Australia New Zealand Food Authority, Shellfish Toxins in Food, A Toxicological Review and Risk Assessment, Australia New Zealand Food Authority, Canberra, 2001. 

Murata, M., Isolation and structural elucidation of the causative toxin of the diarrhetic shellfish poisoning, Bull. Jpn. Soc.Sci. Fish, 48, 549, 1982. 

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],... 

Ito, S. and Tsukada, K., Matrix effect and correlation by standard addition in quantitative liquid chromatographic spectrometric analysis of diarrhetic shellfish poisoning toxins, J. Chromatogr., 943, 39 16, 2002. 

Hamano, Y, Kinoshita, Y., and Yasumoto, T. 1986. Enteropathogenicity of diarrhetic shellfish toxins in intestinal models. 

Lee, J.-S., Igarashi, T, Fraga, S., Dahl, E., Hovgaard, R, and Yasumoto, T. 1989. Determination of diarrhetic shellfish toxins in various dinoflagellate species. JApp/fftyco/1, 147-152. 

Leira, E, Alvarez, C., Cabado, A.G., Vieites, J.M., Vieytes, M.R., and Botana, L.M. 2003. Development of a F actin-based live-cell fluorimetric microplate assay for diarrhetic shellfish toxins. Ana/Bioc/jem 317, 129-135. 

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