Variations in the distribution of okadaic acid in organs and biological fluids of mice related to diarrhoeic syndrome

Okadaic acid (OA) is the main toxin produced by dinoflagellates which can a ccumulate in the hepatopancreas of mussels and cause diarrhetic shellfish p oisoning in consumers. This toxin is also a tumour promoter and a specific potent inhibitor of protein phosphatases 1 and 2A. No specific target organ is known for this toxin. This study concerns the distribution of [H-3]OA i n organs and biological fluids of Swiss mice having received a single dose per os of AO (50 mu g/kg). The determination of the toxin extracted from mo use organs 24 h after administration of [H-3]OA and derivatised with 9-anth ryldiazomethane (ADAM) before HPLC and fluorescent detection showed the hig hest concentration in intestinal tissue and stomach. This distribution was even more pronounced in intestinal tissue, when animal were given per os 90 mu g/kg which induced diarrhoea. The high concentrations of [H-3]- OA in i ntestinal tissues and contents 24 h after administration demonstrates a slo w elimination of OA. When the dose of OA was increased from 50-90 mu g/kg, the concentrations of the toxin in the intestinal content and faeces increa sed proportionally. A good correlation was found between an increase of OA in the intestinal tissue and the diarrhoea in animals given 90 mu g/kg oral ly. Moreover OA was present in liver and bile and in all organs including s kin and also fluids. Altogether these results confirmed an enterohepatic ci rculation of OA as previously shown. These data also revealed that in acute OA intoxication the concentration of the toxin in the intestinal tissues r eaches cytotoxic concentrations in accordance with the diarrhoea which is t he main symptom of OA poisoning.