Okadaic Acid and Other Diarrheic Toxins: Toxicological Profile

Okadaic acid (OA) and its derivatives are toxic lipophilic polyethers produced by marine dinoflagellates and accumulated in filter-feeding organisms, where they can undergo biotransformation. The ingestion of marine shellfish contaminated by these toxins causes a gastrointestinal illness in humans known as diarrhetic shellfish poisoning (DSP). OA and its analogues are weak tumor promoters and specific inhibitors of serine/threonine protein phosphatases. Inhibition of these enzymes affects various cellular processes, including the events at the basis of diarrhea and tumor promotion, although other mechanisms of action cannot be excluded. Studies in rodents indicate that these diarrheic toxins are absorbed through the gastrointestinal tract and distributed in the whole body, inducing toxic effects. Their lethal oral doses after acute administration in mice are 2\u20135 times higher than intraperitoneal ones, with the small intestine and liver as main target organs, while repeated oral OA exposure affects mainly the forestomach, lymphoid organs, pancreas, and, at ultrastructural level, myocardium. The increasing number of toxicological studies on OA, including cytotoxicity, genotoxicity, neurotoxicity, and tumor promotion, suggests that the adverse effects of this compound and/or its analogues could not be limited to acute hazards related to diarrhea induction but can also pose a significant risk after sub(chronic) exposure. Thus, further studies are needed to assess the adverse effects of long-term exposure to low doses of diarrheic toxins. Moreover, periodic monitoring of seafood and harmful algal species in the seawater is recommended to protect public health from foodborne poisonings and to minimize negative economic impacts to the shellfish industry