Ameliorating Effects of Tempol on Methotrexate-Induced Liver Injury in Rats

Biomed Pharmacother. 2018 Jun;102:758-764. doi: 10.1016/j.biopha.2018.03.147. Epub 2018 Apr 5.


Methotrexate (MTX) is used in the treatment of certain types of cancers and chronic inflammatory illnesses, although the clinical use of MTX is limited due to its adverse effects, the most common of which are hepatotoxicity and nephrotoxicity. In the present study, we demonstrate the protecting influence of tempol related to oxidative stress in MTX-induced liver toxicity in rats using histopathological and biochemical parameters. The rats were divided into four groups: control group (group 1), tempol group (group 2), MTX group (group 3) and MTX + tempol group (group 4). The control group (group 1) received physiological saline for 10 days; the tempol group (group 2) received 30 mg/kg i.p. for 10 days, the MTX group (group 3) received a single dose of 20 mg/kg intraperitoneal (i.p.) on the fourth day of the study, and the MTX + tempol group (group 4) received a single dose of 20 mg/kg i.p. on the fourth day, followed by tempol 30 mg/kg i.p. for 10 days. Malondialdehyde (MDA), myeloperoxidase (MPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were found to be significantly lower in the MTX + tempol group then in the MTX group; while superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were found to be higher in the MTX + tempol group than in the MTX group. Tempol ameliorates vacuolic degeneration, inflammation and necrosis in MTX-treated rats. Our study demonstrates that tempol treatment after MTX administration ameliorates oxidative damage in liver tissue in rats.

Keywords: Liver injury; Methotrexate; Tempol.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Caspase 3 / metabolism
  • Catalase / metabolism
  • Cyclic N-Oxides / pharmacology*
  • Female
  • Glutathione Peroxidase / metabolism
  • Liver / drug effects
  • Liver / enzymology
  • Liver / injuries*
  • Liver / pathology
  • Malondialdehyde / metabolism
  • Methotrexate / adverse effects*
  • Oxidants / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats, Wistar
  • Spin Labels
  • Superoxide Dismutase / metabolism
  • bcl-2-Associated X Protein / metabolism


  • Antioxidants
  • Cyclic N-Oxides
  • Oxidants
  • Proto-Oncogene Proteins c-bcl-2
  • Spin Labels
  • bcl-2-Associated X Protein
  • Malondialdehyde
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Caspase 3
  • tempol
  • Methotrexate