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Home » Archive » 2014

TDK conference 2014

In vitro drug metabolism in rabbits
Szentmiklósi Diána - year 4
SZIU Faculty of Veterinary Science, Department of Pharmacology and Toxicology
Supervisor: Orsolya Palócz

Abstract:

The hepatic cytochrome-P450 (CYP450) enzymes play an important role in the metabolism of xenobiotics, in which the chemical structure of these substances (eg. drugs, toxins) changes. These enzymes participate in phase I. of drug metabolism, forming a more reactive and more polar group in the molecule. In the mammalian species mainly three CYP families (CYP1A, CYP2 and CYP3A) are involved in the metabolism of drugs. A given compound may be a substrate, inductor or inhibitor of the various CYP isozymes.

Because of the central role in drug metabolism, the CYP450 system has been in recent decades and is currently an object of numerous researches. The activity of certain subfamilies and isozymes are studied often in laboratory animal species, and then predicted the level of the expected drug metabolism and interactions in humans. There are often differences between the species, furthermore interspecies, breeds and strains.

The aim of our study was to investigate the applicability of a luminescent method in rabbit, which is anyway developed to demonstrate the activity of human cytochrome enzymes.

During our study we have treated rabbit primary hepatocyte cultures with specific inductors and inhibitors to the examined CYP450 (CYP1A1, CYP1A2, CYP3A6) enzymes, then we have detected the activitiy of the enzymes with the luminescent method.

Our results show that luminescent method developed to demonstrate human cytochrome activity can be used also for rabbit CYP450 enzymes, especially in CYP1A subfamily. The effects of typical inductors and inhibitors were well characterized.



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