Year : 2012  |  Volume : 3  |  Issue : 3  |  Page : 248-253

Metformin ameliorates methotrexate-induced hepatotoxicity

1 Department of Pharmacology, Medical College, Kufa University, Kufa Najaf street, Najaf, Iraq
2 Department of Surgery, Medical College, Kufa University, Kufa Najaf street, Najaf, Iraq
3 Department of Pharmacology and Therapeutics, College of Medicine, Qadisiyah University, Diwaniyah, Iraq

Correspondence Address:
Fadhil G Al-Amran
Department of Surgery, Box C-320, 12700 E 19th Avenue, Aurora, CO 80045, USA

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0976-500X.99426

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Objective: To study the effect of metformin on amelioration of hepatotoxicity induced by methotrexate. Materials and 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). Conclusion: 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.

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