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Updated: Jun 6, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Effects of ionophores on liver CYP1A and 3A in male broilers
1College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Abstract:
The effects of ionophore antibiotics on the enzyme activity, protein and mRNA expression levels of cytochrome P450 (CYP) isoenzymes were investigated in liver from male Arbor Acres (AA) broiler chicks. Monensin, salinomycin and maduramycin at the dosage of 120, 60, and 5 mg/kg were administered in feed for 14 days. CYP1A and CYP3A activities were quantitated using cocktail probe drugs and a high performance liquid chromatographic (HPLC) assay at the 15th day; the protein expressions of CYP1A and CYP3A were detected by Western blot. CYP1A4, CYP1A5 and CYP3A37 mRNA levels were detected by real-time polymerase chain reaction (real-time PCR). Monensin, salinomycin and maduramycin had no effect on caffeine metabolism, protein expression and mRNA expression, but did induce dapsone metabolism, increasing CYP3A protein expression. However, there was no change in CYP3A37 mRNA expression as compared with the control group. It is suggested that ionophore antibiotics may have an induction effect on CYP3A expression and enzyme activity and that such effect might be related to the posttranscriptional regulation of its protein expression. Consideration of the enhanced metabolism of other drugs used simultaneously with ionophores is therefore recommended.
Insights
Ionophore antibiotics like monensin, salinomycin, and maduramycin increased cytochrome P450 (CYP) 3A protein expression in broiler chicks. This suggests potential drug interactions due to altered drug metabolism.
Area of Science:
- Pharmacology
- Biochemistry
- Animal Science
Background:
- Cytochrome P450 (CYP) enzymes are crucial for drug metabolism in animals.
- Ionophore antibiotics are commonly used in poultry production.
- Understanding their impact on CYP enzymes is vital for animal health and food safety.
Purpose of the Study:
- To investigate the effects of three ionophore antibiotics (monensin, salinomycin, maduramycin) on CYP enzyme activity, protein, and mRNA expression in broiler chicks.
- To determine if these antibiotics influence the metabolism of specific probe drugs.
Main Methods:
- Male Arbor Acres broiler chicks were fed diets containing monensin, salinomycin, or maduramycin for 14 days.
- CYP1A and CYP3A enzyme activities were measured using HPLC assays with probe drugs.
- Protein expression of CYP1A and CYP3A was analyzed via Western blot.
- mRNA levels of CYP1A4, CYP1A5, and CYP3A37 were quantified using real-time PCR.
Main Results:
- Ionophore antibiotics did not affect caffeine metabolism or CYP1A/CYP3A mRNA expression.
- A significant increase in dapsone metabolism and CYP3A protein expression was observed.
- No significant change in CYP3A37 mRNA levels was detected, indicating post-transcriptional regulation.
Conclusions:
- Ionophore antibiotics may induce CYP3A protein expression and enzyme activity in broiler chicks.
- This induction appears to be regulated post-transcriptionally.
- Concurrent use of ionophores with other drugs requires careful consideration due to potential alterations in drug metabolism.
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