Methotrexate inhibits the glyoxalase system in vivo in children with acute lymphoid leukaemia.
Eur J Cancer
; 40(15): 2287-92, 2004 Oct.
Article
en En
| MEDLINE
| ID: mdl-15454255
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/m(2)/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 alpha-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.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Metotrexato
/
Inhibidores Enzimáticos
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Lactoilglutatión Liasa
/
Antimetabolitos Antineoplásicos
Límite:
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Eur J Cancer
Año:
2004
Tipo del documento:
Article
País de afiliación:
Hungria
Pais de publicación:
Reino Unido