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    Journal of Pharmacology and PharmacotherapeuticsNOW IN
    Article

    Metformin ameliorates methotrexate-induced hepatotoxicity

    Najah R. Hadi1, Fadhil G. Al-Amran2★, Asma Swadi3★ Corresponding author

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

    CORRESPONDENCE

    Fadhil G. Al-Amran

    Department of Surgery, Medical College, Kufa University, Kufa Najaf street, Najaf.

    fadhil.al-amran@ucdenver.edu

    Volume 3, Issue 3 · pp. 248–253 · PUBLISHED 2012 · DOI: 10.4103/0976-500X.99426

    View on J Pharmacol. Pharmacother. original site ↗

    ABSTRACT

    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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      Hadi, N. R., Al-Amran, F. G., & Swadi, A. (2012). Metformin ameliorates methotrexate-induced hepatotoxicity. Journal of Pharmacology and Pharmacotherapeutics, 3(3), 248–253. https://doi.org/10.4103/0976-500X.99426