Title:Cytochrome P450 mediated feed additives and antimicrobial interactions in rabbits
Lethaus, Katharina Ragnhild
The use of natural additives in the rabbit industry has increased during the last years, not only due to the European ban on the non-therapeutic use of antibiotic growth promoters and limits on the use of other drugs, but also due to consumers demanding natural products, and therefore synthetic active compounds should be replaced by natural ones. Xenobiotics are metabolized by the cytochrome 450 (CYP) enzyme system. There are specific aspects about the metabolism in rabbits, as e.g. faster metabolism and higher enzyme activity compared to other organisms. Commercially available drinking water substances; a sanguinarine-containing and a fulvic acid product were used, by alone or simultaneously with an antimicrobial agent, tylosin, in different concentrations (0.5, 1, 2.5, 5 mM). The aim of this study is the investigation of possible drug-supplement interactions in rabbits. Primarily, the in vitro hepatic CYP3A6 and CYP2C activity in rabbits was examined. The microsome fraction was isolated from the liver and the cytochrome activity was measured by luminometry using the P450-Glo™ substrates. An antibacterial agent, the tylosin’s and the drinking water supplements’ effect on the CYP450 enzyme system were measured separately, and the effect of fulvic acid and sanguinarine in combination with tylosin on the CYP450 enzyme system was also examined. According to our results, neither the fulvic acid nor the sanguinarine-containing supplements altered the activity of CYP2C and CYP3A6. The tylosin tartrate considerable inhibited the activity of CYP3A6 and only higher concentrations of tylosin (1, 2.5, 5 mM) reduced the activity of CYP2C. Since the fulvic acid and the sanguinarine-containing supplements did not change the activity of the examined cytochrome enzymes in vitro, presumably they are safe to use as additives in rabbit stock even along with drug therapy.