Role of the phytoestrogenic, pro-apoptotic and anti-oxidative properties of silymarin in inhibiting experimental benign prostatic hyperplasia in rats

被引:44
作者
Atawia, Reem T. [1 ]
Tadros, Mariane G. [1 ]
Khalifa, Amani E. [1 ]
Mosli, Hisham A. [2 ]
Abdel-Naim, Ashraf B. [1 ]
机构
[1] Ain Shams Univ, Fac Pharm, Dept Pharmacol & Toxicol, Cairo, Egypt
[2] King Abdulaziz Univ, Fac Med, Dept Urol, Jeddah 21413, Saudi Arabia
关键词
Silymarin; Prostatic hyperplasia; Estrogen receptors; Oxidative stress; Apoptosis; NF-KAPPA-B; ESTROGEN-RECEPTOR-BETA; ANDROGEN RECEPTOR; ER-BETA; STROMAL CELLS; CANCER; EXPRESSION; ALPHA; INDUCTION; ACTIVATION;
D O I
10.1016/j.toxlet.2013.03.002
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Androgen and estrogen play an important role in the pathogenesis of benign prostatic hyperplasia (BPH). Estrogen exerts its action through two distinct estrogen receptors (ERs) either ER-alpha or ER-beta. The phytoestrogenic property of silymarin (SIL) has been previously characterized. Thus, this study examined the protective effect of SIL against testosterone-induced BPH in rats. In an initial dose-response study, SIL in a dose of 50 mg/kg was the most effective in preventing the rise in prostate weight, prostate weight/body weight ratio and histopathologic changes induced by testosterone. Testosterone significantly decreased ER-beta and increased ER-alpha and AR expressions as compared to the control group and these effects were significantly ameliorated by SIL. Furthermore, SIL significantly protected against testosterone-provoked decline in mRNA expression of P21 (WAF1/Cip1) and Bax/Bcl-x(1) ratio as well as caspase-3 activity. SIL minimized the number of proliferating cell nuclear antigen (PCNA) positive cells as compared to testosterone-treated group. Moreover, SIL significantly blunted the inducible NF-kappa B expression and restored the oxidative status to within normal values in the prostatic tissues. Collectively these findings elucidate the effectiveness of SIL in preventing testosterone-induced BPH in rats. This could be attributed, at least partly, to its phytoestrogenic, pro-apoptotic and anti-oxidative properties. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:160 / 169
页数:10
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