Amelioration of Tamoxifen-Induced Oxidative Stress in Rats

Abstract

This study was conducted to investigate the ameliorative effect of silymarin on the oxidative stress induced by tamoxifen (TAM) in female albino rats. Adult female albino rats (180-220 g) were divided into four groups (n=8) treated as follows: (1) control group: rats was treated with 0.5% carboxy methyl cellulose in distilled water by oral route. (2) Tamoxifen group: rats received tamoxifen orally in a dose of 20 mg/kg/day for 14 days. (3) Silymarin (SLM) group: rats received orally 100 mg/ kg /day of silymarin for 14 days and (4) TAM/SLM group: rats received orally 100 mg/ kg /day of silymarin and 20 mg/kg/day of tamoxifen for 14 days. The rats were sacrificed 24 hr after the end of treatment. The results revealed that tamoxifen induced marked increase in relative liver weight and serum levels of ALT, AST and decrease in serum albumin level which were normalized by silymarin administration. Pretreatment with silymarin significantly attenuated tamoxifen-induced increases in malondialdehyde (MDA) in the liver homogenate. The results revealed that the activities of lysosomal enzymes acid phosphatase (ACP), β-N-acetyl glucosaminidase (β-NAG) and β- galactosidase (β-GAL) were significantly decreased in TAM-treated animals while concomitant treatment by silymarin caused marked decrease in the activities of the three enzymes (P < 0.05). TAM significantly decreased reduced glutathione (GSH) and glutathione reductase (GR) levels in the liver homogenate, while concomitant treatment with silymarin blunted the decreased levels of GSH and GR (P < 0.05). Our results revealed the potential antioxidant and hepatoprotective effect of silymarin against TAM-induced hepatotoxicity. So, it may be worthy to consider the beneficial use of silymarin as supplement with tamoxifen therapy.

Keywords: Tamoxifen, Silymarin, hepatotoxicity, lysosomal enzymes, GSH, GR, MDA