Variation of Hepatic Methotrexate 7-hydroxylase Activity in Animals and Humans

IUBMB Life. 1999 Dec;48(6):607-11. doi: 10.1080/713803569.

Abstract

This study deals with individual and species variations in the converting activity of methotrexate (MTX) to 7-hydroxymethotrexate in animals and humans. When MTX 7-hydroxylase was assayed in six human liver cytosols, a 48-fold range of intersubject variation of the activity was observed. The variations were correlated to the concentrations of aldehyde oxidase activity in human subjects assayed with benzaldehyde as a substrate. Species differences of liver MTX 7-hydroxylase activity were also observed. The activity was highest in rabbits, followed by rats, hamsters, and monkeys but was undetectable in dogs. Strain differences of MTX 7-hydroxylase activity based on aldehyde oxidase activity were also observed in rats and mice. The results suggest that aldehyde oxidase functions as MTX 7-hydroxylase in livers of animals and humans, and the observed differences of MTX 7-hydroxylase activity are due to variations in the amount of aldehyde oxidase present.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Animals
  • Child, Preschool
  • Cricetinae
  • Dogs
  • Female
  • Guinea Pigs
  • Humans
  • Liver / enzymology*
  • Macaca mulatta
  • Male
  • Mesocricetus
  • Methotrexate / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Middle Aged
  • Mixed Function Oxygenases / metabolism*
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Mixed Function Oxygenases
  • Methotrexate