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

Abstract

<jats:p> 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 [<jats:sup>3</jats:sup>H]OA in organs and biological fluids of Swiss mice having received a single dose per os of AO (50 mg/kg). The determination of the toxin extracted from mouse organs 24 h after administration of [<jats:sup>3</jats:sup>H]OA and derivatised with 9-anthryldiazo methane (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 mg/kg which induced diarrhoea. The high concentrations of [<jats:sup>3</jats:sup>H]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 mg/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 mg/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. </jats:p>

Toxic Action Reevaluation of Okadaic Acid, Dinophysistoxin-1 and Dinophysistoxin-2: Toxicity Equivalency Factors Based on the Oral Toxicity Study

“…The early appearance of diarrhea after acute oral administration of OA and the presence of the toxin in these feces indicated an elimination of part of administered toxin before absorption. However, gastrointestinal absorption and distribution of DTX1 occurs rapidly since it can be detected in urine in the first 3 h, although some content remains in feces [24,38]. About DTX2, excretion was greater in the last hours as was previously reported [29].…”

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“…The high concentrations in the intestinal tissue and contents after 24 hours are indicative of slow elimination of OA. The facts that OA was present in the liver and bile and all organs and fluids, and that concentrations in intestinal content were approximately 2-7 fold higher than in the faeces after 24 hours, indicate that enterohepatic circulation occurs (Matias et al, 1999). In studies in mice using anti-OA antibody, OA was detected in lung, liver, heart, kidney and small and large intestines 5 min.…”

“…show that OA is well absorbed by the gastrointestinal tract. Of the respective doses, 49% were found in intestinal tissue plus contents, and 12 % of the dose was found in 24-h urine samples (Matias et al, 1999).…”

Combined cytotoxicity and genotoxicity of a marine toxin and seafood contaminant metal ions (chromium and cadmium)

“…Previous studies have shown that OA is widely distributed in mammals after consumption (Matias et al, 1999b), the main effects being in the intestinal tract where it is responsible for DSP (Kumagai et al, 1986;Sueoka and Fujiki, 1997).…”