Repeated oral co-exposure to yessotoxin and okadaic acid: a short term toxicity study in mice.

The polyethers yessotoxin (YTX) and okadaic acid (OA) are two marine algal toxins frequently associated as edible shellfish contaminants. Seafood contamination by these compounds, also at low concentrations and for a long period of time, can increase the possibility of their simultaneous and repeated ingestion, with possible synergistic toxic effects. Thus, in vivo toxicity by repeated oral exposure to a combination of fixed doses of YTX and OA (1 mg YTX/kg and 0.185 mg OA/kg, daily for 7 days) was investigated in mice, in comparison to that of each toxin alone. No mortality, signs of toxicity, diarrhea or hematological changes was induced by the toxins co-administration or by the single toxins. Light microscopy revealed changes at gastric level (multifocal subacute inflammation, erosions and epithelial hyperplasia) in 2/5 mice co-administered with the toxins. In animals dosed only with OA, epithelial hyperplasia of forestomach and slight focal subacute inflammation of its submucosa were noted. No changes were induced by the treatment with YTX. Ultrastructural analysis of the heart revealed some cardiomyocytes with "loose packing" of myofibrils and aggregated rounded mitochondria in mice co-administered with the toxins or with YTX; OA-treated mice showed only occasional mitochondrial assemblage and dilated sarcomeres. Thus, the combined oral doses of YTX (1 mg/kg/day) and OA (0.185 mg/kg/day) did not exert cumulative or additive toxic effects in mice, in comparison to the single toxins.

Yessotoxins: a toxicological overview.

Yessotoxins (YTXs) are polyciclic ether compounds produced by phytoplanktonic dinoflagellates and accumulated in filter feeding shellfish. These toxins can be ingested by humans through contaminated seafood consumption. Initially, YTXs were classified as Diarrhetic Shellfish (DS) toxins but the biological activity of these compounds, which lack of diarrheogenic effects, differs from that of diarrheic toxins. Thus, YTXs have been recently classified as a separate group of algal toxins. Yessotoxin (YTX), homoyessotoxin and 45-hydroxy-homoyessotoxin are lethal after intraperitoneal injection to mice but not after single or repeated oral administration. The target organ seems to be the cardiac muscle cells, where these toxins induce light and electron microscopy ultrastructural changes not only after intraperitoneal injection, but also after oral exposure. On the other hand, di-desulfo-yessotoxin affects liver and pancreas, where it induces fatty degeneration. The mechanisms at the basis of the cardiac effects of YTX and homoyessotoxins are still not completely understood. No short term and chronic toxicity data are available as well as pharmacokinetic studies are lacking. Nevertheless, YTX is known to exert different in vitro activities, such as changes of intracellular calcium and cyclic AMP levels, alteration of cytoskeletal and adhesion molecules, caspases activation and opening of the permeability transition pore of mitochondria. This review reports the current knowledge on the in vivo toxicity and in vitro effects of these toxins.