Methotrexate: pentose cycle and oxidative stress.
The effect of methotrexate (MTX) and leucovorin (LCV) on pentose cycle enzymes and the activity of enzymes involved in enzyme defence mechanisms against ROS in HeLa cells, were studied. The effect of MTX was also investigated on the cellular levels of glutathione. MTX inhibited the activity of glucose-6-phosphate and 6-phosphogluconate dehydrogenases. The activities of glutathione reductase and gamma-glutamylcysteine synthetase were also inhibited by the drug. No effect was observed on the activities of catalase, superoxide dismutase or transketolase. LCV had no effect on any of the enzymes studied. MTX decreased the cellular levels of glutathione (70 per cent), while the presence of LCV and glutamine did not interfere with the effect of MTX. The net results appear to show that the biological situation resulting from treatment with MTX leads to a reduction of effectiveness of the antioxidant enzyme defence system.
Babiak
R M
RM
Departamento de Bioquímica, Universidade Federal do Paraná Curitiba, Brasil.
Campello
A P
AP
Carnieri
E G
EG
Oliveira
M B
MB
D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005973:Glutamine / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology; D008727:Methotrexate / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D010544:Peroxidases / Q000378:metabolism; D010734:Phosphogluconate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism; D014174:Transketolase / Q000378:metabolism
D000975:Antioxidants; D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D017382:Reactive Oxygen Species; D005973:Glutamine; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D010544:Peroxidases; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D014174:Transketolase; D019881:Aminoacyltransferases; C093784:glutathione gamma-glutamylcysteinyltransferase; D005978:Glutathione; D002955:Leucovorin; D008727:Methotrexate