Acute oral toxicity in mice of a new palytoxin analog: 42-Hydroxy-palytoxin

作者：Tubaro A^*; Del Favero G; Beltramo D; Ardizzone M; Forino M; De Bortoli M; Pelin M; Poli M; Bignami G; Ciminiello P; Sosa S

来源：Toxicon, 2011, 57(5): 755-763.

DOI：10.1016/j.toxicon.2011.02.009

• 42-Hydroxy-palytoxin (42-OH-PLTX)
• Algal toxins
• Acute oral toxicity
• Mice
• Light microscopy

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 mu g/kg), administered by gavage, induced scratching, jumping, respiratory distress, cyanosis, paralysis and death of mice, with an LD(50) of 651 mu g/kg (95% confidence limits: 384-1018 mu g/kg) within 24 h. Hematoclinical analyses showed increased plasma levels of lactate dehydrogenase and aspartate-aminotransferase at doses of 600 mu g/kg and above, as well as of alanine-aminotransferase, creatine phosphokinase and potassium ions at >= 848 mu g/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 mu g/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 nix (EC(50) = 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.

• 出版日期2011-4