title: Metformin ameliorates methotrexate-induced hepatotoxicity.
abstract: OBJECTIVE
  To study the effect of metformin on amelioration of hepatotoxicity induced by methotrexate.
  
  
  METHODS
  After a 2-weeks of acclimatization period, the animals were randomly separated into three groups (seven rabbits each), all groups were maintained on standard chow diet throughout the experiment (8 weeks). Group 1 was treated with normal saline water (control), Group 2 with methotrexate (MTX, hepatotoxic), and Group 3 with MTX plus metformin. Induction of hepatotoxicity was carried out by administration of MTX to the rabbit in a dose of 0.25 mg/kg /day i.m. for 8 weeks.
  
  
  RESULTS
  The treatment with MTX to rabbits for 8 weeks resulted in significant changes in serum liver enzymes, as compared to the baseline group. SGOT, SGPT, ALP, and bilirubin were significantly increased (P < 0.001), while total serum protein was significantly decreased. Similarly, 8 weeks of MTX treatment produced significant (P < 0.001) prolongation in PT. PTT was not significantly changed. It was found that serum MDA levels and SOD activity were significantly increased (P < 0.001), while serum GSH levels were significantly decreased (P < 0.001). Adding metformin to MTX is found to be significantly (P < 0.001) reduced the liver function test and shortening of PT and a significant increase in TSP (P < 0.001).
  
  
  CONCLUSIONS
  It can be concluded that administration of metformin restored the altered liver function parameters and produced significant improvement in liver histopathological findings. Therefore, this additive drug possesses hepatoprotection against MTX-induced hepatotoxicity.
authors.affiliation: Department of Pharmacology, Medical College, Kufa University, Kufa Najaf street, Najaf, Iraq.
authors.forename: Najah R
authors.initials: NR
authors.lastname: Hadi
authors.forename: Fadhil G
authors.initials: FG
authors.lastname: Al-Amran
authors.forename: Asma
authors.initials: A
authors.lastname: Swadi
keywords: Hepatotoxicity; metformin; methotrexate