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

来源：

TOXICOLOGY LETTERS | 2013年 / 219卷 / 02期

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

页码：160 / 169

页数：10

共 54 条

[51] An endocrine pathway in the prostate, ERβ, AR, 5α-androstane-3β,17β-diol, and CYP7B1, regulates prostate growth [J].

Weihua, Z ;

Lathe, R ;

Warner, M ;

Gustafsson, JÅ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (21) :13589-13594

[52] Silymarin: A review of its clinical properties in the management of hepatic disorders [J].

Wellington, K ;

Jarvis, B .

BIODRUGS, 2001, 15 (07) :465-489

[53]

Young C., 2004, U.S. Patent, Patent No. [6,680,342, 6680342]

[54] Orphan nuclear receptor estrogen-related receptor-β suppresses in vitro and in vivo growth of prostate cancer cells via p21WAF1/CIP1 induction and as a potential therapeutic target in prostate cancer [J].

Yu, S. ;

Wong, Y. C. ;

Wang, X. H. ;

Ling, M. T. ;

Ng, C. F. ;

Chen, S. ;

Chan, F. L. .

ONCOGENE, 2008, 27 (23) :3313-3328

← 1 2 3 4 5 6 →