Methotrexate inhibits the glyoxalase system in vivo in children with acute lymphoid leukaemia

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Abstract

The inhibition of glyoxalase I leads to antitumour activity through the accumulation of methylglyoxal. Our earlier observations suggested that methotrexate (MTX) may affect the glyoxalase system. This prompted a serial study of the drug on this metabolic pathway. Ten children with acute lymphoid leukaemia (ALL), admitted to our department between January 2002 and July 2003, were enrolled. Plasma d-lactate was assayed before, 24 and 72 h after the start of four consecutive MTX infusions (5 g/m2/24 h) in each patient. Inhibition of glyoxalase I was tested in vitro, using human erythrocyte lysates and yeast enzyme. The elevated initial plasma d-lactate levels (P < 0.02) fell significantly (P < 0.001) in response to 24 h MTX infusions. In vitro, MTX, folic and folinic acids inhibited the activity of glyoxalase I. Thus, MTX seems to affect the α-oxoaldehyde metabolism in vivo, as a likely consequence of glyoxalase I inhibition. This action probably contributes to the anticancer activity and toxicity of the drug.

Original languageEnglish
Pages (from-to)2287-2292
Number of pages6
JournalEuropean Journal of Cancer
Volume40
Issue number15
DOIs
Publication statusPublished - Oct 2004

Keywords

  • Diabetes
  • Folic acid
  • Folinic acid
  • Glyoxalase
  • Leukaemia
  • Methotrexate
  • Methylglyoxal
  • Thiamine
  • d-Lactate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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