| Distribution of Brevetoxin (PbTx-3) in Mouse Plasma: Association with High-Density Lipoproteins Ricky T. Woofter, Page C. Spiess, and John S. Ramsdell Marine Biotoxins Program, Center for Coastal Environmental Health and Biomolecular Research, National Oceanic and Atmospheric Administration-National Ocean Service, Charleston, South Carolina, USA Abstract
We investigated the brevetoxin congener PbTx-3 to determine its distribution among carrier proteins, including albumin and blood lipoproteins. Using a radiolabeled brevetoxin tracer (PbTx-3) , we found that 39% of the radiolabel remained associated with components in mouse plasma after > 15 kDa cutoff dialysis. Of this portion, only 6.8% was bound to serum albumin. We also examined the binding of brevetoxin to various lipoprotein fractions. Plasma, either spiked with PbTx-3 or from mice treated for 30 min with PbTx-3, was fractionated into different-sized lipoproteins by iodixanol gradient ultracentrifugation. Each fraction was then characterized and quantified by agarose gel electrophoresis and brevetoxin radioimmunoassay, respectively. In both the in vitro and in vivo experiments, the majority of brevetoxin immunoreactivity was restricted to only those gradient fractions that contained high-density lipoproteins (HDLs) . Independent confirmation of brevetoxin binding to HDLs was provided by high molecular weight (100 kDa cutoff) dialysis of [3H]PbTx-3 from lipoprotein fractions as well as a scintillation proximity assay using [3H]PbTx-3 and purified human HDLs. This information on the association of brevetoxins with HDLs provides a new foundation for understanding the process by which the toxin is delivered to and removed from tissues and may permit more effective therapeutic measures to treat intoxication from brevetoxins and the related ciguatoxins. Key words: blood, brevetoxin, ciguatoxin, HDL, lipoprotein, plasma. Environ Health Perspect 113:1491-1496 (2005) . doi:10.1289/ehp.8010 available via http://dx.doi.org/ [Online 23 June 2005]
Address correspondence to: J.S. Ramsdell, Coastal Research Branch, Center for Coastal Environmental Health and Biomolecular Research, NOAA-National Ocean Service, 219 Fort Johnson Rd., Charleston, SC 29412. Telephone: (843) 762-8510. Fax: (843) 762-8700. E-mail: john.ramsdell@noaa.gov The National Ocean Service (NOS) does not approve, recommend, or endorse any proprietary product ormaterial in this publication. No reference shall be made to NOS, or to this publication furnished by NOS, in any advertising or sales promotion which would indicate or imply that NOS approves, recommends, or endorses any proprietary product or proprietary material mentioned herein or which has as its purpose any intent to cause directly or indirectly the advertised product to be used or purchased because of NOS publication. The authors declare they have no competing financial interests. Received 11 February 2005 ; accepted 23 June 2005.
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