International Journal of Medical Science and Clinical Research Studies ISSN(print): 2767-8326, ISSN(online): 2767-8342 Volume 03 Issue 06 June 2023 Page No: 1090-1094 DOI: https://doi.org/10.47191/ijmscrs/v3-i6-10 , Impact Factor: 6.597 1090 Volume 03 Issue 06 June 2023 Corresponding Author: Mohammed J Manna A Review on Hepatotoxic Effects of Methotrexate Therapy with Possible Strategies that May Counteract Hepatotoxicity Mohammed J Manna 1 , Murtadha S Jabur 2 , Atheer S. Alsabah 3 , Luma Saad Baqir 4 1,4 College of Dentistry, Mustansiriyah University, Iraq 2 College of Pharmacy, National University for Science and Technology, Iraq. 3 College of Pharmacy, Al-Bayan University, Iraq. ABSTRACT ARTICLE DETAILS Methotrexate, inhibitor of a dihydrofolate reductase, is a chemotherapeutic treatment applied in many kinds of tumors as an anti-metabolite. also, Methotrexate applied to treat different other disorders, including diseases of autoimmunity, such as psoriasis, rheumatism, vasculitis and ulcerative colitis and Crohn’s disease. However, Methotrexate induces toxic effects on neurons, kidney toxicity, and liver damage, also Methotrexate have been associated with elevation risk of hepatic injury, fibrosis and cirrhosis. Methotrexate work as a dihydrofolic acid analog that binds to the dihydrofolate reductase enzyme that prevent the synthesis of tetrahydrofolic acid, that is essential synthesis of DNA. Although folic acid combine with Methotrexate therapy to prevent hepatotoxic effects, folic acid may reduce therapeutic effects of Methotrexate so recent research focus incorporation of new agent to counteract Methotrexate induced hepatotoxicity that include vitamin B12, vitamin E, N-acetylcysteine, melatonin, Erdosteine, inulin, Ferulic acid, Human placental extract, Natural plant extract (flavonoids). These agents are promising to counteract Methotrexate induced hepatotoxicity. Materials and methods: A comprehensive literature review on different published articles hepatotoxic effects of methotrexate and was carried out by electronic research on Medline, PubMed, Google scholar, and Cochrane Libran data bases using different searching terms related to prevention of methotrexate induced hepatotoxicity. The article focusses on clinical studies in different regions in the period of 2018-2022. Objective: To search for new update modality preventive therapy for methotrexate induced liver damage Results: Recent study oriented for the prevention and treatment of methotrexate associated with hepatotoxicity. KEYWORDS: Methotrexate induced hepatotoxicity, antioxidant. Published On: 13 June 2023 Available on: https://ijmscr.org/ INTRODUCTION Methotrexate inhibitor for dihydrofolate reductase, is an anti- metabolite applied as a chemotherapy for many kinds of tumors 1 . Methotrexate involved in treatment of other disease involving diseases of autoimmunity, like psoriasis, rheumatism, vasculitis and ulcerative colitis and Crohn’s disease (2-5) . However, Methotrexate may cause neurotoxicity 6 , nephrotoxicity 7 , and hepatotoxicity (8,9) , Methotrexate have been linked to increase risk of liver damage, fibrosis and cirrhotic damage. Methotrexate work as a dihydrofolate analog which binds to the dihydrofolate reductase enzyme by preventing the production of tetrahydrofolic acid, that essential for production of DNA. Many factors that may increase risk of methotrexate induced hepatotoxicity, involving alcohol consumption, aging, timing for doses with Methotrexate and its amount of drug consumed by patient, medical history for liver disease, obesity, diabetic desease, hepatitis B or C virus infection and taking medicine associated with liver injury 8 . Moreover, non-alcoholic fatty injury, were liver steatosis is detected without heavy alcohol consumption 10 which has been similarly associated with Methotrexate therapy 11 . As dangerous adverse effects also low doses, Methotrexate may cause liver fibrotic damage and even cirrhosis. Minimum Methotrexate doses in chronic plaque psoriatic lesion was detected to have a 7% increase risk for development of cirrhotic liver injury , and aminotransferase rises up to triple times than standard level that found in 8% of the patients examined 13 . The incidence of Methotrexate -induced hepatic fibrosis and cirrhosis 14 .