Toxicity and pathophysiology of palytoxin congeners after intraperitoneal and aerosol administration in rats
| Autor: | Sara C. McGrath, David M. Kulis, Aysegul Nalca, Jonathan R. Deeds, Virginia Livingston, Donald M. Anderson, David W. Dyer, Jo-lynne W. Raymond, Patricia Ruiz-Olvera, Ondraya M Frick, Mark A. Poli, Sara Ruiz, Christopher W. Schellhase |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0106 biological sciences
0301 basic medicine medicine.medical_specialty medicine.drug_class Pharmacology Toxicology Monoclonal antibody medicine.disease_cause 01 natural sciences Article 03 medical and health sciences chemistry.chemical_compound Cnidarian Venoms Palytoxin medicine Animals Potency Aerosols Acrylamides Dose-Response Relationship Drug Molecular Structure Toxin 010604 marine biology & hydrobiology Rats Inbred F344 Pathophysiology Rats 030104 developmental biology chemistry Mechanism of action Toxicity Dinoflagellida Female Marine Toxins Histopathology medicine.symptom Injections Intraperitoneal |
| Zdroj: | Toxicon. 150:235-250 |
| ISSN: | 0041-0101 |
| Popis: | 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 tissue histopathology after 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 (0.92, 1.93, 1.81 and 3.26 μg/kg, for the 50:50 mix, 42-OH-PLTX, PLTX, and ovatoxin-a, respectively) were consistent with published values, although some differences from the published literature were seen. The aerosol LD50 values (0.063, 0.045, 0.041, and 0.031 μg/kg for the 50:50 mix, 42-OH PLTX, PLTX, and ovatoxin-a, respectively) confirmed the exquisite potency of PLTX suggested by the literature. The tissue histopathology 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, salivary glands, and adrenal glands. Despite some differences, these results suggest commonalities in potency and mechanism of action among these PLTX congeners. |
| Databáze: | OpenAIRE |
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