Repeated oral co-exposure to yessotoxin and okadaic acid: A short term toxicity study in mice

• Published in: Toxicon (Oxford) Vol. 76; pp. 94 - 102
• Main Authors: Sosa, S., Ardizzone, M., Beltramo, D., Vita, F., Dell'Ovo, V., Barreras, A., Yasumoto, T., Tubaro, A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.12.2013
• Subjects: acute toxicity; Algae; Animals; Biocompatibility; cardiomyocytes; diarrhea; Female; forestomach; heart; Heart - drug effects; hyperplasia; inflammation; Ingestion; light microscopy; Marine Toxins - administration & dosage; Marine Toxins - toxicity; Mice; Mice, Inbred Strains; mitochondria; mortality; Myocardium - ultrastructure; Okadaic acid; Okadaic Acid - administration & dosage; Okadaic Acid - toxicity; oral exposure; Oxocins - administration & dosage; Oxocins - toxicity; Repeated daily oral administration; sarcomeres; Seafood; seafoods; shellfish; Toxic; Toxicity; Toxicity Tests; Toxicology; Toxins; Transaminases - blood; Yessotoxin; Okadaic acid; Mice; Yessotoxin; Toxicity; Repeated daily oral administration
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2013.09.014

The polyethers yessotoxin (YTX) and okadaic acid (OA) are two marine algal toxins frequently associated as edible shellfish contaminants. Seafood contamination by these compounds, also at low concentrations and for a long period of time, can increase the possibility of their simultaneous and repeated ingestion, with possible synergistic toxic effects. Thus, in vivo toxicity by repeated oral exposure to a combination of fixed doses of YTX and OA (1 mg YTX/kg and 0.185 mg OA/kg, daily for 7 days) was investigated in mice, in comparison to that of each toxin alone. No mortality, signs of toxicity, diarrhea or hematological changes was induced by the toxins co-administration or by the single toxins. Light microscopy revealed changes at gastric level (multifocal subacute inflammation, erosions and epithelial hyperplasia) in 2/5 mice co-administered with the toxins. In animals dosed only with OA, epithelial hyperplasia of forestomach and slight focal subacute inflammation of its submucosa were noted. No changes were induced by the treatment with YTX. Ultrastructural analysis of the heart revealed some cardiomyocytes with “loose packing” of myofibrils and aggregated rounded mitochondria in mice co-administered with the toxins or with YTX; OA-treated mice showed only occasional mitochondrial assemblage and dilated sarcomeres. Thus, the combined oral doses of YTX (1 mg/kg/day) and OA (0.185 mg/kg/day) did not exert cumulative or additive toxic effects in mice, in comparison to the single toxins. •Repeated combined oral doses of yessotoxin and okadaic acid were not lethal for mice.•Gastric lesions were noted after co-treatment with the toxins or okadaic acid alone.•Co-treatment with the toxins or yessotoxin induced heart ultrastructural changes.•No cumulative/additive effects are induced by combined oral doses of these toxins.