[The effect of monensin, tiamulin and the simultaneous administration of both substances on the microsomal mixed...

The influence of Monensin, Tiamulin and the simultaneous administration of the two substances on the microsomal, mixed function oxidases was studied on cockerels. Monensin was seen to cause a slight depression in the amount of cytochrome P-450 and cytochrome b5 as well as in the activities of aniline-p-hydroxylase, p-nitrophenol-hydroxylase and p-nitroanisole-O-demethylase. Tiamulin induced a moderate increase in the amount of cytochrome P-450 and in the activities of aniline-p-hydroxylase, p-nitrophenol-hydroxylase and aminopyrine-N-demethylase. The combined administration of monensin and tiamulin resulted in marked induction of the microsomal enzymes; the amount of cytochrome P-450 reduced by metyrapone or carbon monoxide increased 2.5 or 2-times, respectively, and the activities of the tested microsomal hydroxylases and demethylases showed also an expressed increase. At the same time the formation of lipid peroxides also markedly increased and the GSH concentration was reduced. In conclusion, the results of the investigations indicate that the simultaneous application of monensin and tiamulin cause a marked induction of the drug-metabolizing microsomal enzymes and a significant increase in the lipid peroxide formation.