الفهرس 
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Abstract
Methotrexate was i.p. injected once weekly for 7 weeks in 2 doses (0.1 and 0.2 mg/100 gm b.wt. to mature male rats. Blood and tissue samples (liver and spleen) were collected at the end of the study for determination of the effect on some liver function parameters (AST, ALT and GGT), total protein, albumin and globulins, IgG, IgM, SOD, GSH, CAT, MDA, IL-6 , IL-1B, comet assay and Histopathological changes.
Methotrexate induced a significant increase in serum activities of AST, ALT, GGT, MDA, IL-6 and IL-1B and a significant decrease in serum activities of SOD, GSH and IgG and IgM as well as serum total protein, albumin and globulins when compared was normal control group. The comet assay revealed a significant increase in all parameters of DNA fragmentation. The histopathological changes revealed various degenerative changes in liver and spleen. In all studies the effects were dose dependent.
The obtained results revealed that Methotrexate afforded deleterious effects on all liver enzyme parameters and anti-oxidative enzymes as well as immunoglobulins as well as DNA damage, thus patients treated with Methotrexate showed be supplemented with antioxidants, hepatoprotectives and immunostimulants to avoid the side effects of Methotrexate.