Protective Role of Silymarin Against Methotrexate Induced Nephropathy in Rabbits

ABSTRACT The experiment aimed to investigate the protective effects of Silymarin (SMN) against methotrexate (MTX) induced nephropathy in rabbits. In a randomized control trial, a total of 20 rabbits were allocated into 4 different groups each containing 5 rabbits. The Control group was received orally normal saline equivalent to the amount daily for 14 days. The MTX group was received intraperitonially (i.p) 20 mg/kg body weight (b.w) of Methotrexate for two dose (day 1 and day 7). The SMN group was received orally (p.o) 100 mg/kg b.w of Silymarin daily for 14 days. The MTX+SMN group was received Methotrexate (20 mg/kg b.w, i.p for two doses at the day 1 and day 7) with silymarin (100 mg/kg b.w, p.o for 14 days). The dosage of 100 mg/kg b.w of Silymarin was chosen based on previously published studies demonstrating its efficacy in nephroprotection without toxicity. Gross and histomorphometric analysis and hematobiochemical test were performed. SMN treated group showed significantly ( p  < 0.05) higher body weight gain after the experimental trial. The MTX treated group showed significantly higher weight gain of the kidney. Histomorphometric analyses of kidney revealed nephropathy i.e degenerate cortical tubules characteristics, glomerular shrinkage and perivascular aggregation of lymphocyte, vacuolization and disrupted proximal convoluted tubule (PCT) in MTX treated group and well organized glomerular structure and normal tubule in SMN treated group. MTX treated group showed significant ( p  < 0.05) decreased of total red blood cell (RBC), hemoglobin and significant increased of serum urea and creatinine compared with control group. The MTX+SMN group showed biometrical and hematobiochemical parameters were tends to the control group. Methotrexate had adverse impact and silymarin had beneficial effect on kidney gross and histomorphometry, hematobiochemical parameters in rabbits so far silymarin can use parallelly with Methotrexate to reduce its adverse effects.