Effects of silymarin on methotrexate-induced nephrotoxicity in rats

Abstract

Methotrexate (MTX) is widely used in the treatment of various malignancies and nononcological diseases but its use has been limited by its nephrotoxicity. Silymarin (SLY), a natural flavonoid, has been reported to have antioxidant, anti-inflammatory and anti-apoptotic effects. This study was carried out to determine whether SLY exerts a protective effect against MTX-induced nephrotoxicity. Rats were divided into six groups: Group 1 (saline, i.p., single injection), Group 2 (0.5% carboxymethyl cellulose (CMC), by gavage once daily for five consecutive days), Group 3 (SLY, 300 mg/kg per day, i.p. for five consecutive days), Group 4 (MTX, 20 mg/kg, i.p., single injection), Group 5 (MTX + CMC similarly as groups 2 and 4) and Group 6 (MTX + CMC + SLY similarly as groups 2, 3 and 4). Histopathologic alterations including apoptotic changes of the kidney were evaluated. MTX injection exhibited dilated Bowman's space, inflammatory cell infiltration, glomerular and peritubular vascular congestion and swelling of renal tubular epithelium cells. Apoptotic cell death was also markedly increased in renal tubules after MTX administration. SLY treatment resulted in statistically significant amelioration in the histological alterations and reduced the number of TUNEL-positive cells as compared with the MTX treated rats (p50.05). In conclusion, SLY treatment leads to a reduction on MTX-induced renal damage in rats. Since SLY is safe and acceptable for human consumption, further studies to define the exact mechanism of the protecting effect of SLY on MTX-induced nephrotoxicity and the optimum dosage of this compound would be useful.

Comparative Nephroprotective Effects of Silymarin, N-Acetylcysteine, and Thymoquinone Against Carbon Tetrachloride-Induced Nephrotoxicity in Rats

“…Additionally, apoptosis was increased. Silymarin treatment led to significant histopathologic improvements in the kidney sections (44). The literature therefore supports our study's finding that silymarin is nephroprotective.…”

Histopathologcal Effects of Methotrexate on Rat Kidney –An Experimental Study on Wistar Albino Rats.

“…The findings of present study are also similar with those reported by Dabak DO et al [17] which showed dilated Bowman's space, inflammatory cell infiltration, glomerular and peritubular vascular congestion and swelling of renal tubular epithelial cells. Erboga M et al [18] showed prominent degenerative changes with tubular degeneration, tubular dilatation, tubular cell swelling, cellular vacuolization, glomerular congestion and degeneration in the renal cortical tissues.…”

The ameliorating effect of silymarin against vancomycin-induced apoptosis and inflammation in rat liver

“…Anticancer activity of SL was also reported against several cancer types [1]. Some studies reported that SL suppresses caspase activation [9] and prevents apoptotic cell development [2,24]. Our results suggested that pre-treatment of high dose (200 mg/kg/day) of SL was significantly reduced caspase activities against VA-induced hepatotoxicity and concentration of SL is important for balancing oxidant-antioxidant status in liver tissues.…”

“…SL has been widely used for the treatment of liver and gall bladder disorders, and also has beneficial effects on different organ illnesses and broad range of cancers [8]. Hepatoprotective [3], anti-apoptotic, strong antioxidant [8], anti-inflammatory, immunomodulatory [8,9], membrane-stabilizing [7], and antiviral properties [9,10] of SL have been reported in previous studies. Experimental and clinical studies also indicated that antioxidant activity of SL reduces inflammatory reaction, promotes hepatocyte regeneration, and inhibits fibrogenesis [7].…”