Can leflunomide prevent methotrexate induced liver toxicity?

Abstract

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 kappaB activation. Leflunomide also presents antioxidant activity. In this experimental study, we aimed to investigatethe 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 methotrexatewas 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 tissueswere collected for analyzed serum alanine aminotransferase, alkaline phosphatase, superoxide dismutaseactivity, myeloperoxidase activity, glutathione levels and assessment of histopathology.Results: Leflunomide treatment significantly ameliorated total histopathologic score according to semiquantitativescale 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 Kupffercells score were 0.2+0.6 and 2.5+1.01 respectively, p = 0.001). The serum alanine aminotransferase, alkalinephosphatase levels were lower and glutathione levels, myeloperoxidase activity, and superoxide dismutaseactivity were similar between leflunomide treated and untreated methotrexate toxicity groups.Conclusion: Leflunomide treatment ameliorated methotrexate induced liver toxicity in this experimental model.