Jasim Ali Hussein, Abu-Raghif Ahmed Rahmah, Hussein Zeena Ayad
Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.
Drug Res (Stuttg). 2025 Jul;75(6):225-234. doi: 10.1055/a-2576-4153. Epub 2025 Apr 28.
Benign prostatic hyperplasia is a common urological condition in aging men. The anthelmintic agent niclosamide ethanolamide exhibits a wide range of pharmacological activities. This study aimed to evaluate the protective effect of niclosamide ethanolamide in testosterone propionate-induced benign prostatic hyperplasia in rats along with elucidating the probable mechanism of action by investigating the influence on PPAR-γ and Wnt/β-catenin. 40 male Wistar rats were divided randomly into 4 groups. The healthy (control) group, received daily oral and subcutaneous administration of the vehicle. The Induced (TP) group, received only a daily dose of testosterone propionate 3 mg/kg, SC for 28 days. The treated groups (TP+FIN) and (TP+NE), received a concomitant administration of a daily dose of testosterone propionate along with finasteride 5 mg/kg/day and niclosamide ethanolamide 50 mg/kg/day respectively through oral gavage. Animals were euthanized on day 30 of the experiment and prostate tissue samples were collected to evaluate prostate index, prostate hyperplastic markers by ELISA, and gene expression by RT-qPCR. Results revealed that niclosamide ethanolamide significantly reduced prostate index compared to the induced (TP) group (P<0.0001). The agent nearly normalized BPH markers including 5α-reductase type-2 enzyme, dihydrotestosterone, and PCNA compared to the induced (TP) group (P<0.0001). The agent reduced the tissue level of β-catenin while elevating PPAR-γ to control levels (P<0.05). The current study revealed that NE can help prevent BPH in rats by upregulating the PPAR-γ receptor and inhibiting the Wnt pathway.
良性前列腺增生是老年男性常见的泌尿系统疾病。驱虫药氯硝柳胺乙醇胺具有广泛的药理活性。本研究旨在评估氯硝柳胺乙醇胺对丙酸睾酮诱导的大鼠良性前列腺增生的保护作用,并通过研究其对PPAR-γ和Wnt/β-连环蛋白的影响来阐明其可能的作用机制。40只雄性Wistar大鼠随机分为4组。健康(对照)组每日经口和皮下给予赋形剂。诱导(TP)组仅每日皮下注射3mg/kg丙酸睾酮,共28天。治疗组(TP+FIN)和(TP+NE)分别通过灌胃同时给予每日剂量的丙酸睾酮以及非那雄胺5mg/kg/天和氯硝柳胺乙醇胺50mg/kg/天。在实验第30天对动物实施安乐死,并收集前列腺组织样本,以评估前列腺指数、通过ELISA检测前列腺增生标志物以及通过RT-qPCR检测基因表达。结果显示,与诱导(TP)组相比,氯硝柳胺乙醇胺显著降低了前列腺指数(P<0.0001)。与诱导(TP)组相比,该药物使包括2型5α-还原酶、二氢睾酮和增殖细胞核抗原在内的良性前列腺增生标志物几乎恢复正常(P<0.0001)。该药物降低了β-连环蛋白的组织水平,同时将PPAR-γ提升至对照水平(P<0.05)。当前研究表明,氯硝柳胺乙醇胺可通过上调PPAR-γ受体和抑制Wnt通路来帮助预防大鼠良性前列腺增生。