Abstract
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.