İnvestigation op the protective effects of silymarin on the metotrexate-induced hepatotoxicity in rats

Metotreksat (MTX) is a widely used drug for treatment of many kind of cancer and also some inflamatory diseases. However, there are many side effects including hepatotoxicity. In this study, it was purpossed to examine the protective effects of Silymarin on rat liver damage caused by MTX administration.Total of 36 adult Sprague Dawley rats were used. The animals were diveded for 6 grupus including 6 animals each group. During 5 days of experimental stage, a single dosage of 0.5 ml saline was applied intraperitonealy (i.p.) to Group I, orally(CMC) was applied to Group II, 300 mg/kg Silymarin were orally given to Group III, intraperitoneally a single 20 mg/kg dosage of MTX was applied to Group IV, intraperitoneally a single 20 mg/kg dosage of MTX and orally 300 mg/kg Silymarin were bapplied to Group V, i.p. a single 20 mg/kg dosage of MTX and orally CMC were applied to Group VI. At the end of the experimental stage, the rats were decapitated and liver tissue removed for futher research. For the routine light microscopic evaluation, the tissues were bloced in paraffine. The histochemical stains were applied to the section obtained from the bloced tissue. The observerd finding were evaluated and photoghraphed.In histological evaluation, there were no statistically differences between first 3 groups. However, histopathological findings were similar in Group IV and Group VI. These findings are including vascular congestion, sinusoidal dilatation, periportal inflammation, hepatocyte with pyknotic nuclei, fragmentary degenerate hepatocyt, important decrease in glycogen stores and minimal hepatic steatosis.In addition, in these two groups, TUNEL positivity, Bax and Caspase 3 positive cells were found to be hight compared to other experimental groups. However, the tissue damaged was relatively low in Group V in which Silymarin apllied.As a conclusion, tissue damage caused by MTX did not totaly restored by silymarine application but partially improvoment was observed.Key words: Methotrexate, Silymarin, TUNEL, Bax, Caspase, CMC