Can leflunomide prevent methotrexate induced liver toxicity?

Purpose: long-term clinical use of methotrexate is connected with a raised risk of liver injury and fibrosis. leflunomide is a disease-modifying drug. leflunomide has a powerful inhibitory effect on nuclear factor kappa b activation. leflunomide also presents antioxidant activity. in this experimental study, we aimed to investigate the effects of leflunomide treatment on methotrexate -induced hepatotoxicity. materials and methods: thirty-nine rats were divided into 4 groups. a single dose of 20mg/kg methotrexate was injected intraperitoneally for methotrexate-induced hepatotoxicity. after induction, leflunomide (10 mg/kg) was administered into the stomach for consecutive 5 days. then, serum samples and homogenated liver tissues were collected for analyzed serum alanine aminotransferase, alkaline phosphatase, superoxide dismutase activity, myeloperoxidase activity, glutathione levels and assessment of histopathology. results: leflunomide treatment significantly ameliorated total histopathologic score according to semiquantitative scale compared to the untreated group, (pathological score 1.1+0.7 versus 5.1+2 respectively, p<0,01). leflunomide treatment significantly ameliorated kuppfer cell activation. (elevation of the activated kupffer cells score were 0.2+0.6 and 2.5+1.01 respectively, p = 0.001). the serum alanine aminotransferase, alkaline phosphatase levels were lower and glutathione levels, myeloperoxidase activity, and superoxide dismutase activity were similar between leflunomide treated and untreated methotrexate toxicity groups. conclusion: leflunomide treatment ameliorated methotrexate induced liver toxicity in this experimental model.