Possible interactions between supplements and antimicrobials in chickens

Abstract

Feed supplements are frequently used in the chicken industry to promote the health and increase the weight gain of the flock. Commercially available supplements were used in the present study, the effect of them on the cytochrome P450 enzymes, which are important in drug metabolism, was investigated. In addition, we investigated the effect of a poultry probiotic, Bacillus licheniformis supernatant on the activity of CYP enzymes in vitro. A possible interaction between an antimicrobial agent, tiamulin, and the applied additives was also tested in vitro. A sanguinarine-containing supplement and a fulvic acid preparation were administered orally for five consecutive days to four broilers, per treatment at a dose of 50 and 250 mg/kg body weight, respectively. After the last treatment day, the microsomal fraction was isolated from each of the livers, from which the activity of the CYP1A1 and CYP2C isoenzymes was determined by luminometry. In addition, a 5% solution of the Bacillus licheniformis supernatant was added in vitro to the control microsomal samples, and tiamulin fumarate at concentrations of 0, 0.5, 1, 2.5, 5 mM were added to the microsomal samples of both the control and the feed supplemented individuals and the CYP enzymes activity was monitored. The sanguinarine-containing preparation did not alter the activity of the examined isoenzymes, but treatment with fulvic acid increased the level of CYP1A1 enzyme. Tiamulin caused a significant reduction in the activity of CYP1A1 even at the lowest applied concentration, while CYP2C activity did not change at 0.5 and 1 mM concentrations of tiamulin. However, the activity of CYP2C decreased to 40% due to 2.5 mM tiamulin fumarate and reduced the enzyme activity to almost zero at 5 mM. There was no interaction between the feed additives and the tiamulin drug on the CYP1A1 enzyme. However, tiamulin at 2.5 mM concentration, with the addition of supplements, resulted in a stronger inhibition of CYP2C enzymes than alone. Overall, the drinking water supplements used at a tenfold dose did not cause significant changes in the activity of CYP2C enzymes, which play a major part in the drug metabolism of birds, so the regular dose of supplements can be safely used in the chicken flock even in parallel with drug therapy.