Oxidative effect of methotrexate administration in spinal cord of rabbits

J Pak Med Assoc. 2011 Nov;61(11):1096-9.


Objective: To study the potential effect of Methotrexate (MTX) on lipid peroxidation and activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) two important endogenous anti-oxidant enzymes.

Methods: Twenty healthy male Newzland rabbits weighting 1500-1800 g were divided into two groups. One group was considered as the MTX groups and the other was considered as control group. Rabbits had free access to food and tap water. Rabbits in MTX group received a single dose of MTX, 20 mg/kg intraperitoneally, a similar volume of saline was administered to control group. After 6 days rabbits were uteinized and spinal tissue excised for biochemical studies.

Results: GPX and SOD activities in spinal tissue in rabbits of MTX group significantly reduced after MTX administration compared to control group(P = 0.002 vs 0.18). An increase in the tissue MDA level was seen in the MTX group, suggesting increased lipid peroxidation. Levels of MDA were significantly higher in MTX group compared to control group (P = 0.002).

Conclusion: Our data suggests that MTX treatment induces oxidative tissue damage on the spinal tissue, as assessed by increased lipid peroxidation and decreased GPX and SOD levels, so decreasing oxidative stress by anti-oxidant agents may play a key role in attenuating spinal cord injury.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / metabolism
  • Antimetabolites, Antineoplastic / pharmacology*
  • Antimetabolites, Antineoplastic / toxicity
  • Antioxidants / metabolism
  • Free Radical Scavengers / metabolism
  • Glutathione Peroxidase / drug effects*
  • Glutathione Peroxidase / metabolism
  • Lipid Peroxidation / drug effects*
  • Male
  • Methotrexate / metabolism
  • Methotrexate / pharmacology*
  • Methotrexate / toxicity
  • Oxidative Stress / drug effects*
  • Rabbits
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism
  • Superoxide Dismutase / drug effects*
  • Superoxide Dismutase / metabolism


  • Antimetabolites, Antineoplastic
  • Antioxidants
  • Free Radical Scavengers
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Methotrexate