Decrease of adenosine deaminase activity and increase of the lipid peroxidation after acute methotrexate treatment in young rats: protective effects of grape seed extract

Cell Biochem Funct. 2010 Jan;28(1):89-94. doi: 10.1002/cbf.1627.


The methotrexate (MTX) is an anti-folate used to treat cancer and some inflammatory diseases. The efficacy of MTX is often limited by its severe toxicity. The present study was undertaken to determine whether Grape seed (Cabernet Sauvignon) extract (GSE) could ameliorate the MTX-induced oxidative injury and the effect on adenosine deaminase activity (ADA) in rats. The rats were pretreated with 50 mg/kg of GSE, i.p., prior to MTX administration (10 mg/kg, i.p.) with a second dose given 4 h and a third dose 16 h after MTX administration. Biochemical parameters were investigated 48 h after the last MTX administration. The administration of MTX increased thiobarbituric acid reactive species (TBARS) levels in hippocampus, kidney and liver, whereas induced a significant decreased in the ADA activity in the cerebral cortex, kidney and liver tissues. MTX administration significantly increased the activity of ALT(alanine aminotransferase) and urea levels and decreased uric acid levels in the serum. Urinary uric acid levels decreased in the MTX group when compared to those of the control group. The GSE along with MTX-administration significantly reversed these parameters toward to near normal. These results indicated that GSE could reduce hepatic and nephritic damage induced by MTX-treatment in young rats therefore having free radical scavenging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / metabolism*
  • Alanine Transaminase / blood
  • Animals
  • Grape Seed Extract / pharmacology*
  • L-Lactate Dehydrogenase / blood
  • Lipid Peroxidation / drug effects*
  • Male
  • Methotrexate / toxicity*
  • Rats
  • Rats, Wistar
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Uric Acid / blood
  • Uric Acid / urine


  • Grape Seed Extract
  • Thiobarbituric Acid Reactive Substances
  • Uric Acid
  • L-Lactate Dehydrogenase
  • Alanine Transaminase
  • Adenosine Deaminase
  • Methotrexate