Publication Date:
2022-05-25
Description:
Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Toxicon 150 (2018): 235-250, doi:10.1016/j.toxicon.2018.06.067.
Description:
Preparations of palytoxin (PLTX, derived from Japanese Palythoa tuberculosa) and the congeners
42-OH-PLTX (from Hawaiian P. toxica) and ovatoxin-a (isolated from a Japanese strain of
Ostreopsis ovata), as well as a 50:50 mixture of PLTX and 42-OH-PLTX derived from Hawaiian P.
tuberculosa were characterized as to their concentration, composition, in-vitro potency and
interaction with an anti-PLTX monoclonal antibody (mAb), after which they were evaluated for
lethality and pathophysiological effects by intraperitoneal (IP) and aerosol administration to rats.
Once each preparation was characterized as to its toxin composition by LC-HRMS and normalized to
a total PLTX/OVTX concentration using HPLC-UV, all four preparations showed similar potency
towards mouse erythrocytes in the erythrocyte hemolysis assay and interactions with the anti-PLTX
mAb. The IP LD50 values derived from these experiments (1-3 μg/kg for all) were consistent with
published values, although some differences from the published literature were seen. The aerosol
LD50 values (.03-.06 μg/kg) confirmed the exquisite potency of PLTX suggested by the
literature. The pathophysiological effects of the different toxin preparations by IP and aerosol
administration were similar, albeit with some differences. Most commonly affected tissues were
the lungs, liver, heart, kidneys, salivary glands, and adrenal glands. Despite some differences,
these results suggest commonalities in potency and mechanism of action among these PLTX
congeners.
Description:
This work was supported by the Defense Threat Reduction Agency, through the Joint
Program Executive Office for Chemical and Biological Defense, Contract number CB10396.
Additional support to DMA and DLK was provided by National Science Foundation (Grant
OCE-1314642) and National Institutes of Health (NIEHS-1P50-ES021923-01) through the
Woods Hole Center for Oceans and Human Health.
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
