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Methotrexate: pentose cycle and oxidative stress

R M Babiak¹, A P Campello, E G Carnieri

¹Departamento de Bioquímica, Universidade Federal do Paraná Curitiba, Brasil.

Cell Biochemistry and Function

|December 19, 1998

Summary

Methotrexate (MTX) impairs the pentose cycle and antioxidant defenses by inhibiting key enzymes and depleting glutathione levels in HeLa cells. Leucovorin (LCV) does not counteract these MTX effects.

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Area of Science:

Biochemistry
Cell Biology
Pharmacology

Background:

Methotrexate (MTX) is a chemotherapy drug with known cellular effects.
Reactive oxygen species (ROS) can cause cellular damage.
Antioxidant defense systems protect cells from oxidative stress.

Purpose of the Study:

To investigate the impact of methotrexate (MTX) and leucovorin (LCV) on pentose cycle enzymes.
To examine the effect of MTX and LCV on antioxidant enzyme activities and glutathione levels in HeLa cells.

Main Methods:

HeLa cells were treated with MTX and LCV.
Enzyme activities of the pentose cycle and antioxidant defense mechanisms were measured.
Cellular glutathione levels were quantified.

Main Results:

MTX significantly inhibited glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione reductase, and gamma-glutamylcysteine synthetase.
MTX decreased cellular glutathione levels by 70%.
LCV did not affect any measured enzyme activities or mitigate MTX's effects on glutathione.

Conclusions:

MTX treatment compromises the pentose phosphate pathway and the cellular antioxidant defense system.
The observed reduction in glutathione and enzyme inhibition suggests increased susceptibility to oxidative stress.
LCV does not restore the antioxidant capacity affected by MTX.