Abstract
Background: Hepatotoxicity is a common problem in medical practice, most of the commonly used drugs are potentially hepatotoxic. Although Methotrexate is a hepa- toxic drug, it is widely used in the treatment of many cancerous and non-cancerous conditions because of its cytotoxic and immunosuppressant activity. Curcumin con- tains a variety of natural substances with antioxidant properties, it is widely used in folk medicine.Antioxidant activity of Curcumin can reduce liver cell injury induced by Methotrexate administration.
 Objective: The research aims to study the methotrexate hepatoxicity on rabbits, and the hepatoprotective activity of Curcumin.
 Materials and Methods: Thirty white domestic rabbits were bought from animal market and grouped randomly into three groups; control group received intraperitoneal normal saline, methotrexate group received 6.5 mg/Kgm body weight intraperitoneal methotrexate, and curcumin group received oral Curcumin in addition to intraperitoneal methotrexate.
 Results: The study showed abnormal liver function tests, INR, liver tissues oxida- tive markers, and liver cell injury on histopathology in Methotrexate group, and normal findings in Curcumin groups.
 Conclusion: It is concluded that the Methotrexate is a hepatotoxic drug. The results also shoe that the concomitant administration of Curcumin reduced hepatotoxicity.
 Recommendation: It is recommended to use of Curcumin in clinical practice as a food supplement to patient receiving methotrexate to reduce hepatotoxicity.
Highlights
Methotrexate (MTX) is a widely used immunosuppressant and anticancer Drug [1]
Grading of liver cell injury depending on grading system using serological findings introduced by Council for International Organizations of Medical Sciences (CIOMS)toxicity scale can be summarized as follows: Methotrexate group one rabbit was mild grade +, three were moderate grade ++, and six were rabbits moderate to severe grade +++.Grading of liver cell injury in Curcumin group was one rabbit mild grade +, and nine was normal grade 0
The more the liver cell damage seen on histopathology, the more the alterations in these serum parameters.The scores of liver cells injury depending on serum parameters, and per scoring system introduced by CIOMS [17], were scores were 0 in control group, in Methotrexate group one rabbit scored mild 1+, three moderate ++, and six moderate to severe +++.While in Curcumin group, one rabbit scored mild score +, and nine scored 0
Summary
Methotrexate (MTX) is a widely used immunosuppressant and anticancer Drug [1]. It is used in clinical practice against variety of neoplastic and non-neoplastic diseases especially autoimmune diseases like systemic lupus erythematosus, psoriasis, inflammatory bowel diseases, and rheumatoid arthritis [2] [3] [4] [5] [6].Methotrexate is a folic acid antagonist because of its folic acid reeducates inhibitory capability ,its chemical structure is (4-amino-N10-methyl folic acid), and its anti-cancer activity is due to inhibition of DNA synthesis resulting in blocking of cell proliferation [7]. Methotrexate (MTX) is a widely used immunosuppressant and anticancer Drug [1]. It is used in clinical practice against variety of neoplastic and non-neoplastic diseases especially autoimmune diseases like systemic lupus erythematosus, psoriasis, inflammatory bowel diseases, and rheumatoid arthritis [2] [3] [4] [5] [6]. Methotrexate is a hepatoxic drug, it is widely used in the treatment of many cancerous and non-cancerous conditions because of its cytotoxic and immunosuppressant activity. Curcumin contains a variety of natural substances with antioxidant properties, it is widely used in folk medicine.Antioxidant activity of Curcumin can reduce liver cell injury induced by Methotrexate administration.
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