Study on the inhibitory effect of furafylline and troleandomycin in the 7-methoxyresorufin-O-demethylase and nifedipine oxidase activities in hepatic microsomes from four poultry species using high-performance liquid chromatography coupled with fluorescence and ultraviolet detection

J Pharm Biomed Anal. 2019 Feb 5:164:148-154. doi: 10.1016/j.jpba.2018.10.031. Epub 2018 Oct 22.

Abstract

The present study reports the in vitro studies with furafylline and troleandomycin (TAO) as specific inhibitors of activities 7-methoxyresorufin-O-demethylase (MROD) and nifedipine oxidase, catalyzed by cytochrome P450 1 A2 (CYP1 A2) and 3A4 human enzymes, respectively, in hepatic microsomes of quail, duck, turkey and chicken. The results suggest that in chicken and quail the MROD activity is carried out by orthologs CYP1 A4 and 1 A5, meanwhile in duck and turkey by a CYP1 A5 ortholog. The nifedipine oxidase activity is carried out by orthologs of the CYP3A family in the four bird species. The use of furafylline and TAO significantly decreased these activities (P < 0.05) and suggested that the biotransformation of resorufin methyl ether (RME) may be related to more than one avian ortholog.

Keywords: 7-methoxyresorufin-O-demethylase activity; Avian orthologs; Furafylline; Nifedipine oxidase activity; Troleandomycin.

MeSH terms

  • Animals
  • Biotransformation / drug effects
  • Chromatography, High Pressure Liquid / instrumentation
  • Chromatography, High Pressure Liquid / methods
  • Cytochrome P-450 Enzyme Inhibitors / pharmacology*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Nifedipine / metabolism
  • Oxazines / metabolism
  • Poultry / metabolism*
  • Theophylline / analogs & derivatives*
  • Theophylline / pharmacology
  • Troleandomycin / pharmacology*

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Oxazines
  • 7-methoxyresorufin
  • Cytochrome P-450 Enzyme System
  • Theophylline
  • furafylline
  • Troleandomycin
  • methoxyresorufin-O-demethylase
  • Nifedipine