A Review on Hepatotoxic Effects of Methotrexate Therapy with Possible Strategies that May Counteract Hepatotoxicity

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