Alteration of avian hepatic cytochrome P450 gene expression and activity by certain feed additives

Abstract

We investigated the effect of four feed additives, namely β-glucan, a drinking water acidifier (DWA), a sanguinarine-containing product (SN) and fulvic acid, on hepatic cytochrome P450 (CYP) mRNA expression and CYP enzyme activity in chickens. The test substances were given to the chickens in the recommended dose or in tenfold dose. The administration of 5 mg/kg body weight (bw) β-glucan and 0.1 ml/kg bw DWA for five days decreased the relative gene expression of CYP1A4 and CYP2C23a. The dosing of 50 mg/kg bw β-glucan, 5 and 50 mg/kg bw SN, 1 ml/kg bw DWA and 250 mg/kg bw fulvic acid doubled the hepatic CYP1A4 activity. The activity of CYP2C and CYP3A remained unchanged. Avoidance of CYP1A-mediated feed-drug interactions requires accurate dosing of β-glucan, DWA and fulvic acid. According to our results, no treatment resulted in excessive or less CYP2C and CYP3A protein formation, which reduces the risk of potential feed additive-drug interactions in chickens. However, the administration of feed additive SN containing a plant alkaloid should be avoided concomitantly with CYP1A-metabolised medicines.