Comparative metabolism and disposition of ethoxyquin in rat and mouse. II. Metabolism

Xenobiotica. 1996 Jun;26(6):597-611. doi: 10.3109/00498259609046736.

Abstract

1. The major pathways of ethoxyquin (EQ) metabolism in both the rat and mouse are O-deethylation and conjugation to endogenous substrates. 2. The two major EQ-derived metabolites excreted in rat urine were in the form of sulphate conjugates, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline sulphate, and 1,2,3,4-tetrahydro-3,6-dihydroxy-4-methylene-2,2-dimethylquinoline sulphate. The latter apparently arises from an intramolecular rearrangement of the 3,4-epoxide of ethoxyquin. 3. Mouse urine contained one major glucuronide, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline glucuronide as well as one major sulphate conjugate, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline sulphate. 4. EQ-derived radioactivity was excreted in rat bile, mainly as GSH conjugates, with little unchanged EQ present. Two of the biliary metabolites are glutathione conjugates of ethoxyquin 3,4-epoxide; the third appears to be a conjugate of either ethoxyquin 7,8-epoxide or 2,2,4-trimethylquinol-6-one.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Bile / metabolism
  • Chromatography, High Pressure Liquid
  • Ethoxyquin / administration & dosage
  • Ethoxyquin / metabolism*
  • Ethoxyquin / urine
  • Feces / chemistry
  • Glucuronates / urine
  • Glucuronidase / metabolism
  • Glutathione / metabolism
  • Kidney / metabolism
  • Liver / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Rats
  • Rats, Inbred F344
  • Sulfates / urine

Substances

  • Antioxidants
  • Glucuronates
  • Sulfates
  • Ethoxyquin
  • Glucuronidase
  • Glutathione