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Molecular characterisation of toxicological properties of the marine biotoxin okadaic acid in in vitro models for the human intestinal barrier and liver (Okadasäure)

07/2015-06/2018

This third-party funded project is conducted in the framework of the BfR research programme on modern methods in toxicology.

DFG grant number: LA 1177/11-1

Project homepage: -

Project description:

Marine biotoxins are metabolites from algae. Under especially good environmental conditions ("algae bloom"), they form in larger quantities. Since algae are the main source of food of water-filtering mussels, this means that marine biotoxins such as okadaic acid  are also ingested and accumulate in the flesh of the mussels. When humans eat mussels containing high levels of okadaic acid, this results in the typical diarrhoeic mussel poisoning which predominantly causes problems of the intestinal tract. These acute effects, which are confined to the intestinal tract, are well researched. What is less well researched are the carcinogenic and highly embryotoxic properties of okadaic acid. They can occur when the marine biotoxin overcomes the intestinal barrier, enters the blood stream, and additional toxic metabolites are then formed in the liver. Whether this actually occurs depends on the quantity of ingested okadaic acid. In the research project, the scientists investigated how the intestinal wall protects the body from okadaic acid in low concentrations and why in the presence of high concentrations in the intestine, this barrier fails. With the help of cell cultures made up of cells from the human intestinal wall, the changes in the barrier properties of a specific layer of the intestinal mucosa under the influence of okadaic acid and the detoxification mechanism of the intestine are studied. Using human liver cells, the metabolism of this marine biotoxins are additionally investigated, i.e. the formation of metabolites of higher or lower toxicity. It is hoped that an understanding of the molecular connections of detoxification and activation of additional toxic properties will contribute to the identification of unknown toxicity mechanisms of okadaic acid which play a relevant role for the reaction of the body following the consumption of larger doses of this marine biotoxin. The BfR expects the results of this research project to supply additional data on the oral bioavailability, toxicokinetics and metabolism of okadaic acid in order to be able to assess more accurately the health risks it poses to humans.

Project partners:

• Biochemical Institute of Environmental Carcinogens, Germany
• Netherlands Cancer Institute, Netherlands
• Florida International University, USA

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