Protective role of Silymarin in the mitigation of methotrexate induced biometrical and haemato-biochemical alterations of liver in rabbits

Methotrexate (MTX) is a commonly used as chemotherapy drug; However, MTX causes liver damage. Silymarin (SMN) is a plant origin polyphenolic compound with cytoprotective, anti-inflammatory and antioxidant effects. This study was conducted to investigate the hepatoprotective effects of Silymarin. In a randomized control trial, a total of 20 rabbits were allocated into 4 different groups each containing five rabbits for 14 days experimental trial. The control group was given orally normal saline daily for 14 days. The methotrexate (MTX) group was given intraperitonially (IP) 20 mg/kg body weight (BW) of Methotrexate for two doses (day 1 and day 7). The silymarin (SMN) group was given orally 100 mg/kg of Silymarin daily for 14 days. The last methotrexate + silymarin (MTX + SMN) group was given Methotrexate of same doses along with Silymarin. After sacrifice, the liver was collected and examined for gross and histoarchitecture analysis. Blood was collected and serum separated for hematobiochemical test. The SMN group showed significantly (p < 0.001) higher body weight gain. The MTX showed significantly higher weight gain of the liver. Histomorphometric analyses of liver revealed disorganization of hepatic cord, bile duct hyperplasia and proliferation, sinusoidal dilation and portal chorionic inflammatory cells in MTX treated group and highly organized hepatic cord structure, normal sinusoidal spaces in SMN treated group. Methotrexate treated group showed significant (p < 0.05) decreased of total red blood cells (RBC), hemoglobin and significant (p < 0.05) increased of bilirubin and glutamic-oxaloacetic transaminase (SGOT) levels compared with control group. Methotrexate had adverse impact and silymarin had beneficial effect on liver gross and histomorphometry, hematobiochemical parameters in rabbits so fur co-using of Silymarin with Methotrexate may be impactful to reduce the MTX induced hepatotoxicity & hepatopathy.