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 accumulate in the hepatopancreas of mussels and cause diarrhetic shellfish poisoning 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 [3H]OA in organs and biological fluids of Swiss mice having received a single dose per os of AO (50 microg/kg). The determination of the toxin extracted from mouse organs 24 h after administration of [3H]OA and derivatised with 9-anthryldiazomethane (ADAM) before HPLC and fluorescent detection showed the highest concentration in intestinal tissue and stomach. This distribution was even more pronounced in intestinal tissue, when animal were given per os 90 microg/kg which induced diarrhoea. The high concentrations of [3H]OA in intestinal tissues and contents 24 h after administration demonstrates a slow elimination of OA. When the dose of OA was increased from 50-90 microg/kg, the concentrations of the toxin in the intestinal content and faeces increased proportionally. A good correlation was found between an increase of OA in the intestinal tissue and the diarrhoea in animals given 90 microg/kg orally. Moreover OA was present in liver and bile and in all organs including skin and also fluids. Altogether these results confirmed an enterohepatic circulation of OA as previously shown. These data also revealed that in acute OA intoxication the concentration of the toxin in the intestinal tissues reaches cytotoxic concentrations in accordance with the diarrhoea which is the main symptom of OA poisoning.
Matias
W G
WG
Laboratory of Toxicology and Applied Hygiene, Unité de Formation et de Recherche des Sciences Pharmaceutiques, University of Bordeaux II, France.
Traore
A
A
Creppy
E E
EE
D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity; D003967:Diarrhea / Q000139:chemically induced / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000633:toxicity; D051379:Mice; D019319:Okadaic Acid / Q000493:pharmacokinetics* / Q000633:toxicity; D014018:Tissue Distribution
D002273:Carcinogens; D004791:Enzyme Inhibitors; D019319:Okadaic Acid