Methotrexate (MTX) isa folic acid antagonist withanti-inflammatory, anti-proliferative and immunosuppressive activities. MTX is very effective in the treatment of many inflammatory disordersand types of canceras it depleted thehepatic folate stores needed for DNA and protein synthesis. However, this drug has profoundly toxic effect particularly to the liver. Treatment with Ursodeoxycholic Acid (UDCA), a hydrophilic bile acid, is widely used due to its defensive mechanismof liver toxicity.

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... um (Se), one of the essential trace elements, has a protective role as antioxidant in the body. Aim of Study: The present work was designed to evaluate the adverse effect of Methotrexate on the histology of the liver and to investigate the possible protective role of Ursodeoxycholic acid versus Selenium on Methotrexate-induced hepatic toxicity. Material and Methods: Twenty-four adult male albino rats were utilized in the present study. The rats were divided into four groups, each group consisted of six rats. Group I (control group), Group II (receiving Methotrexate only), Group III (Ursodeoxycholic acid -treated group), Group IV (Selenium-treated group). The livers of all rats were removed for investigation using light microscopic, immunohistochemical, histomorphometrical and statistical studies. Results and Conclusion: Methotrexate receiving rats showed massive degenerative changes and loss of demarcation of the hepatocytes. These changes had been partially recovered in rats treated with Ursodeoxycholic acid. Therefore, using Selenium, the degenerative changes were much reduced. The present study concluded that Selenium was more effective in improving the structural changes in rats receiving Methotrexate.