Distribution of Brevetoxin to Lipoproteins in human plasma

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.