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Home » Archive » 2019

TDK conference 2019

Effect of fermented wheat germ extract and proanthocyanidines on intestinal CYP450 enzyme activity
Egyed Petra - year 5
University of Veterinary Medicine Budapest, Department of Pharmacology and Toxicology
Supervisors: Dr. Zita Karancsi, Dr. Orsolya Farkas

Abstract:

The cytochrome P450 enzymatic family, involved in the metabolism of different xenobiotics, has been in the focus of pharmacokinetic studies for a long time. Following oral administration, the bioavailability of the drugs can be altered by the oxidative processes catalyzed by the CYP450 enzymes. Different drugs, xenobiotics and nutrients may interact with each other when combined, thus they can induce or inhibit the CYP450 enzymes. Consequently, their interactions may affect the efficacy of drugs or can even result toxicity. Liver is the organ with the highest CYP abundancy; however, these enzymes can also be found in the intestinal tract.

In our study, we investigated the CYP3A4 enzymatic activity in porcine intestinal epithelial cells (IPEC-J2). Cells were grown on 24-well cell culture plates. After the cell monolayer was formed, grape seed oligomeric proanthocyanidines (50, 100 and 200 μg/ml) and fermented wheat germ extract (FWGE) were administered to the cells in 1%, 2% and 4% concentration. Other cells were treated with a known inducer (phenobarbital, 500µM), and known inhibitor drug (ketoconazole 25μM). As a control, plain DMEM cell culture medium was used. The CYP3A4 activity was measured by chemiluminescent assay. Simultaneous treatment of enterocytes with feed additives and drug compounds was also performed in order to test possible feed-drug interactions.

Phenobarbital has significantly increased the CYP3A4 activity in the enterocytes while ketoconazole resulted in a significant decrease, compared to the controls. Proanthocyanidines showed a significant inducer effect on the CYP3A4 activity in all concentrations. Furthermore, proanthocyanidines combined with ketoconazole increased the CYP3A4 activity significantly. The FWGE application per se did not cause any significant change in the enzyme activity. Decreased activity was found in case of the 2% concentration FWGE treatment when it was combined with ketoconazole. However, a significant increase of enzymatic activity could be observed when FWGE (4%) was combined either with the inducer or with the inhibitor.

In conclusion, our results suggest that proanthocyanidines are intestinal CYP3A4 enzyme inducers, whereas FWGE shows very moderate effect. This indicates that presence of proanthocyanidines could change the metabolism of some drugs in the intestinal tract. Further investigations should focus on the intestinal metabolism of these compounds and in vivo studies also should be done in this field to get a decisive conclusion.



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