Interaction between metabolism and transport of toxicologically relevant compounds in the gastrointestinal barrier

Project

Food and consumer protection

This project contributes to the research aim 'Food and consumer protection'. Which funding institutions are active for this aim? What are the sub-aims? Take a look:
Food and consumer protection

Project code: BfR-LMS-08-1350-007
Contract period: 01.08.2010 - 31.07.2013
Purpose of research: Applied research

The interaction between the cytochrome P450-system, phase II xenobiotic-metabolizing enzymes (XMEs) such as glutathione-S-transferases, UDP-glucuronosyl transferases and sulfotransferases, and ABC-transport proteins is an important part of the mucosa of the small intestine acting as a potential biochemical barrier for nutritional- and eco-toxicological relevant compounds. Intestinal resorption of cancerogenic contaminants of food such as the polycyclic aromatic hydrocarbon (PAHs) benzo[a]pyrene (B[a]P) is affected by the interaction of CYP1A1/CYP1B1, phase II XMEs and ABC-transport proteins. It was shown that excretion of the B[a]P phase II metabolites including B[a]P-glucuronides and B[a]P-sulfates is mediated by breast cancer resistance protein (BCRP) (Ebert et al., 2005). During the first phase of this project we studied the mechanism of detoxification of the ultimate carcinogenic phase I B[a]P metabolite anti-B[a]P-7,8-diol-9,10-epoxide (BPDE). Formation of glutathione (GSH) conjugates mediated by glutathione-S-transferases (GSTs) as well as the excretion of these conjugates was analysed. Our studies also focused on the identification of transport proteins that are involved in GSH conjugate excretion as well as the impact of natural occuring food components like the phytochemical quercetin on the detoxification process.The second phase of the study should elucidate the in vivo situation of the detoxification process of B[a]P. Therefore, toxicokinetic parameters (distribution, metabolism and excretion) of B[a]P should analysed in mice models. It will comprise a) the influence of the flavonol quercetin, b) the role of the BCRP (use of the bcrp-/- knockout mice) as well as c) the role of MRP2/3 using the mrp2/3 double knockout mice.

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