Effects of ionophores on liver CYP1A and 3A in male broilers

L L Zhang1, J R Zhang, Z G Yu

  • 1College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

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.

Related Concept Videos

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess the...
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
Hepatic Drug Excretion: Influencing Factors01:16

Hepatic Drug Excretion: Influencing Factors

The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug binding...
Hepatic Drug Clearance: Effect of Protein Binding01:09

Hepatic Drug Clearance: Effect of Protein Binding

Hepatic clearance is influenced by protein binding based on the drug's extraction ratio. Drugs with high extraction ratios are considered flow-limited and remain unaffected by protein binding during hepatic clearance. On the other hand, drugs with low extraction ratios may be impacted by plasma protein binding, although the extent of this influence depends on the fraction of the drug bound.
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
Bioavailability: Influencing Factors01:22

Bioavailability: Influencing Factors

Bioavailability refers to the extent and rate at which a drug reaches systemic circulation in its active form. Extent refers to the amount of the drug that makes it into circulation, while rate is the speed at which it enters circulation. It is influenced by several factors critical for optimizing drug formulations, dosing regimens, and therapeutic outcomes.Physicochemical properties of drugs and formulationsThe solubility, stability, and dissolution rate of a drug significantly impact its...