title: Role of the phytoestrogenic, pro-apoptotic and anti-oxidative properties of silymarin in inhibiting experimental benign prostatic hyperplasia in rats.
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-α or ER-β. 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 50mg/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-β and increased ER-α 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-xl 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-κB 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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abbasia, Cairo, Egypt.
authors.forename: Reem T
authors.initials: RT
authors.lastname: Atawia
authors.forename: Mariane G
authors.initials: MG
authors.lastname: Tadros
authors.forename: Amani E
authors.initials: AE
authors.lastname: Khalifa
authors.forename: Hisham A
authors.initials: HA
authors.lastname: Mosli
authors.forename: Ashraf B
authors.initials: AB
authors.lastname: Abdel-Naim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011467:Prostate / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000187:drug effects; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000187:drug effects; D012838:Silymarin / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D048789:Phytoestrogens; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D012838:Silymarin; D013739:Testosterone; D053148:Caspase 3