title: Acute oral toxicity in mice of a new palytoxin analog: 42-hydroxy-palytoxin.
abstract: The acute oral toxicity of a new palytoxin congener, 42-hydroxy-palytoxin (42-OH-PLTX), was investigated in female CD-1 mice. The toxin (300-1697 μg/kg), administered by gavage, induced scratching, jumping, respiratory distress, cyanosis, paralysis and death of mice, with an LD₅₀ of 651 μg/kg (95% confidence limits: 384-1018 μg/kg) within 24 h. Hematoclinical analyses showed increased plasma levels of lactate dehydrogenase and aspartate-aminotransferase at doses of 600 μg/kg and above, as well as of alanine-aminotransferase, creatine phosphokinase and potassium ions at ≥ 848 μg/kg. Histology revealed inflammatory lesions in the non-glandular area of the stomach of mice that survived up to 24 h after gavage (424-1200 μg/kg). Although no histological alterations were seen in skeletal and cardiac muscles, changes in some plasma biomarkers (creatine phosphokinase, lactate dehydrogenase) suggested involvement of these tissues in 42-OH-PLTX oral toxicity, in agreement with epidemiological data on seafood poisonings ascribed to palytoxins. Complete recovery of the tissue and hematological changes was observed two weeks post-exposure. Furthermore, 42-OH-PLTX induced in vitro delayed erythrocyte hemolysis at concentrations similar to those of PLTX (EC₅₀ = 7.6 and 13.2 x 10⁻¹² M, respectively). This hemolysis could be completely neutralized by a monoclonal anti-PLTX antibody. The in vivo data, together with the in vitro data recorded for 42-OH-PLTX, seem to indicate Na+/K+-ATPase as one of the key cellular targets of this toxin.
authors.affiliation: Dipartimento dei Materiali e delle Risorse Naturali, Università di Trieste, Via A. Valerio 6, 34127 Trieste, Italy. tubaro@units.it
authors.forename: A
authors.initials: A
authors.lastname: Tubaro
authors.forename: G
authors.initials: G
authors.lastname: Del Favero
authors.forename: D
authors.initials: D
authors.lastname: Beltramo
authors.forename: M
authors.initials: M
authors.lastname: Ardizzone
authors.forename: M
authors.initials: M
authors.lastname: Forino
authors.forename: M
authors.initials: M
authors.lastname: De Bortoli
authors.forename: M
authors.initials: M
authors.lastname: Pelin
authors.forename: M
authors.initials: M
authors.lastname: Poli
authors.forename: G
authors.initials: G
authors.lastname: Bignami
authors.forename: P
authors.initials: P
authors.lastname: Ciminiello
authors.forename: S
authors.initials: S
authors.lastname: Sosa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal; D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid; D003064:Cnidarian Venoms / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006652:Histological Techniques; D007928:Lethal Dose 50; D013058:Mass Spectrometry; D051379:Mice; D011714:Pyrans / Q000008:administration & dosage / Q000633:toxicity*; D013270:Stomach / Q000473:pathology*; D000095702:Polyether Toxins
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D003064:Cnidarian Venoms; D011714:Pyrans; C547187:42-hydroxypalytoxin; D000095702:Polyether Toxins