ISPAC-Tagung

Marine biotoxins are produced by microalgae and may accumulate in high concentrations in filter feeders such as mussels. Okadaic acid (OA) belongs to the group of diarrhetic shellfish poisoning toxins. The human symptoms, following the ingestion of contaminated seafood, include diarrhea, nausea, vomiting and abdominal pain. Toxicokinetic studies showed that OA is absorbed by the gastrointestinal tract and transported to the liver and other organs. It is also known that both the rat and the human hepatic cytochrome P450 monooxygenases (CYP) are able to metabolize this toxin. Currently, no sufficient toxicological data of these OA metabolites exist about their toxicity and mechanisms of action.Pure OA, as well as an OA-S9-mix were used at identical concentrations to treat hamster V79 cells with a low CYP-activity or human HepG2 cells, which express phase I and phase II enzymes. The experiments were performed with both human and rat S9 fraction to demonstrate potential species differences in metabolism of OA or species differences in the toxicity of these OA metabolites. The cell viability was measured using a WST1-assay.In both cell lines the OA metabolites mixtures showed a higher toxicity than the parental substance. OA at a concentration of 300-400 nM which was pre-activated with rat S9-mix was 30% more cytotoxic than OA itself in V79 cells. Similarly strong effects could be observed when OA was pre-activated with human S9-mix. In HepG2 cells, the OA metabolites mixtures after pre-activation with either rat or human S9-mix in a concentration range of 25-250 nM OA, were up to 35 % more toxic than pure OA.These results suggest, that OA is activated after oxidative phase I metabolism into metabolites which possess a higher cytotoxic activity.

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ISPAC-Tagung. 2011.

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