Toxicological studies on palytoxin and ostreocin-D administered to mice by three different routes

• Published in: Toxicon (Oxford) Vol. 54; no. 3; pp. 244 - 251
• Main Authors: Ito, Emiko, Yasumoto, Takeshi
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-09-2009; Elsevier
• Subjects: Acrylamides - administration & dosage; Acrylamides - toxicity; Animal poisons toxicology. Antivenoms; Animals; Biological and medical sciences; Bridged Bicyclo Compounds, Heterocyclic - administration & dosage; Bridged Bicyclo Compounds, Heterocyclic - toxicity; Dose-Response Relationship, Drug; Drug Administration Routes; Histopathology; In vivo toxicity; Intestine, Small - drug effects; Intestine, Small - pathology; Kidney Cortex - drug effects; Kidney Cortex - pathology; Lung - drug effects; Lung - pathology; Male; Medical sciences; Mice; Mice, Inbred ICR; Ostreocin-D (OSD); Ostreopsis siamensis; Palytoxin (PLT); Pyrans - administration & dosage; Pyrans - toxicity; Rats; Rats, Wistar; Stomach - drug effects; Stomach - pathology; Toxicology; Histopathology; In vivo toxicity; Ostreocin-D (OSD); Palytoxin (PLT); In vivo; Vertebrata; Anatomic pathology; Mammalia; Mouse; Toxicity; Animal; Rodentia
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2009.04.009

Palytoxin (PLT) first isolated from zoanthids is extremely lethal to animals by intraperitoneal or intravenous administration but shows little toxicity by gavage dosing in contradiction to the occurrence of fatal poisoning due to PLT-containing seafood.
In order to fully elucidate its potential risks to human we evaluated the toxicological effects via three ways of dosing: gavage, intra-tracheal administration (IT) and sublingual administration. A new analog, 42-hydroxy-3,26-didemethyl-19,44-dideoxypalytoxin isolated from the dinoflagellate
Ostreopsis siamensis and named ostreocin-D (OSD), was also used for comparison, additionally conducted by i.p. By gavage dosing, both toxins did not produce death in mice at the maximum dosage of 200
μg/kg of PLT and 300
μg/kg of OSD. Addition of dietary lipid components to PLT solutions for gavage or use of ulcerated mice did not alter the results, indicating no enhancement of PLT absorption. The two toxins were most toxic by the IT route, causing bleeding and alveolar destruction in the lung and resultant death at 2
μg/kg of PLT, and 11
μg/kg of OSD. Both toxins also induced organ injuries after 24
h when dosed by sublingual administration at about 200
μg/kg. The injuries became fatal when PLT was dosed 2 or 3 times. The results pointed to the necessity of taking multiple approaches to assess the potential health risks due to PLT and its analogs in food and environments.