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Species-dependent formation of okadaic acid metabolites in the liver and identification of involved xenobiotic-metabolizing enzymes
Project
Project code: BfR-LMS-08-1322-533
Contract period: 01.03.2013
- 31.12.2013
Purpose of research: Applied research
Okadaic acid, produced by algae of the genera Dinophysis and Prorocentrum and the consumption of marine seafood contaminated with the odourless and tasteless toxin is responsible for diarrhetic shellfish poisoning syndrome (DSP) in humans. In the presence of a metabolic activating system (liver homogenates, cytochrome P450 (CYP) OA induced both chromosomal damage and micronuclei. These results suggest that the metabolites have a different mode of action than the parent compound. First indications showed that the phase I metabolizing enzymes cause a toxification. In the presence of CYP3A4 alone a detoxification of OA is observed. Furthermore, the toxification is stronger in human systems than in rats systems. The phase I metabolite of OA leading to this toxification is still unidentified. Additionally the effect of phase II metabolism of OA in the human body is not well understood. For a precise risk assessment of OA both the phase I and phase II metabolites and their reaction mechanisms should be analyzed. Therefore xenobiotic enzymes of the liver of both humans and rodents should be used because of known species differences in terms of metabolizing enzymes in the liver. Additionally mainly animal studies with rodents have been incorporated in the risk assessment of OA.
Section overview
Subjects
- Physiology of Nutrition
- Toxicology