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Yessotoxin (YTX), an algal toxin contaminating edible shellfish, was previously shown to induce ultrastructural changes in some cardiac muscle cells of mice after acute (1 and 2mg/kg) or daily repeated oral exposure (1 and 2mg/kg/day, for 7 days). Therefore, the temporal evolution of the ultrastructural myocardial alterations and the development of other signs of toxicity induced by a repeated daily oral administration of YTX (1mg/kg/day, for 7 days) to mice were evaluated within 3 months after the treatment. Symptoms, food consumption, body weight, gross pathology and histopathology of the main organs and tissues were observed, and plasma levels of transaminases, lactate dehydrogenase, creatinine and creatinine phosphokinase were measured. Heart, liver, kidneys and cerebellum were also analysed by transmission electron microscopy. In addition, the blood concentration of YTX was determined by a direct enzyme linked immunosorbent assay (ELISA) 24h after the last toxin administration. No mortality or other treatment-related changes, including histological or hematoclinical parameters, were recorded in mice administered with YTX. Similarly, electron microscopy did not reveal any ultrastructural alteration in the liver, kidneys, and cerebellum associated with YTX treatment. In contrast, changes in cardiac muscle cells near to the capillaries (clusters of rounded mitochondria and disorganization of myofibrils) were observed 24h after the treatment. These changes were also noted 30 days after the toxin administration, while after 90 days no differences in cardiac muscle cells between control and YTX-treated mice were observed, which indicated a recovery of the ultrastructural alterations induced by the toxin.

To better understand the distribution of brevetoxins in lipoproteins, including their role in tissue delivery and toxin elimination in humans, we examined the interaction of brevetoxin congener PbTx-3 with human lipoproteins. In a scintillation proximity assay (SPA) and microtiter equilibrium dialysis, brevetoxin bound linearly to purified human high density, low density, and very low density lipoproteins (HDL, LDL, and VLDL). Both methods demonstrated higher binding capacity per weight for HDL over the other lipoproteins; approximately 50% higher with SPA and 100% higher with equilibrium dialysis. The preferential binding of brevetoxin to HDL particles is consistent with the higher surface to volume ratio of these particles and the association of the toxin with the surface phospholipid/cholesterol domain of the lipoprotein particle. Lipoprotein components were next separated from a well-characterized human plasma sample to determine the mass distribution of brevetoxin within plasma. Equilibrium dialysis of the fractionated and recombined lipoproteins and plasma proteins determined that brevetoxin distributed predominately (>80%) to lipoproteins associating with each lipoprotein class. These results provide useful information to consider human susceptibility differences, such as those based on dyslipidemia, to the transport and elimination of polyether toxins.