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dc.contributor.authorPoli, Mark  Concept link
dc.contributor.authorRuiz-Olvera, Patricia  Concept link
dc.contributor.authorNalca, Aysegul  Concept link
dc.contributor.authorRuiz, Sara  Concept link
dc.contributor.authorLivingston, Virginia  Concept link
dc.contributor.authorFrick, Ondraya  Concept link
dc.contributor.authorDyer, David  Concept link
dc.contributor.authorSchellhase, Christopher  Concept link
dc.contributor.authorRaymond, Jolynne  Concept link
dc.contributor.authorKulis, David M.  Concept link
dc.contributor.authorAnderson, Donald M.  Concept link
dc.contributor.authorMcGrath, Sara  Concept link
dc.contributor.authorDeeds, Jonathan R.  Concept link
dc.date.accessioned2018-08-29T17:50:43Z
dc.date.available2018-08-29T17:50:43Z
dc.date.issued2018-02
dc.identifier.urihttps://hdl.handle.net/1912/10545
dc.descriptionAuthor 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.en_US
dc.description.abstractPreparations 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.en_US
dc.description.sponsorshipThis 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.en_US
dc.language.isoen_USen_US
dc.relation.urihttps://doi.org/10.1016/j.toxicon.2018.06.067
dc.titleToxicity and pathophysiology of palytoxin congeners after intraperitoneal and aerosol administration in ratsen_US
dc.typePreprinten_US


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