Di-(2-ethylhexyl) phthalate promotes benign prostatic hyperplasia through KIF11-Wnt/ß-catenin signaling pathway.

Di-(2-ethylhexyl) phthalate (DEHP) might led to chronic and long-term effects on human organs due to its widespread use and bioaccumulation. Despite some cohorts reporting an association between DEHP exposure and BPH, its underlying mechanisms have not been investigated. Our findings indicate that exposure to DEHP or MEHP (main metabolites of DEHP in the human body) leads to increased prostate weights, elevated prostate index, and notable epithelial thickening in rats. It has been observed to promote BPH-1 cell proliferation with effects ranging from low to high concentrations. Transcriptome sequencing analysis of rat prostate tissues identified KIF11 as the key hub gene. KIF11 is highly expressed after DEHP/MEHP exposure, and knocking down of KIF11 inhibits the MEHP-induced promotion of cell proliferation. Exposure to MEHP has been observed to increase the expression of p-GSK-3ß and elevate the levels of ß-catenin, thereby activating the Wnt/ß-catenin signaling pathway. Knocking down of KIF11 significantly inhibits these effects. Histone H3 at Lysine 27 acetylation (H3K27ac) is implicated in the upregulation of KIF11 expression, as evidenced by the addition of the acetylation inhibitor C646. In summary, our findings established that DEHP exposure could promote BPH through H3K27ac regulated KIF11/Wnt/ß-catenin signaling pathway.

The impact of alpha-1-adrenergic receptor antagonists on the progression of Parkinson disease.

BACKGROUND: Alpha-1-adrenergic receptor antagonists (AARAs) are used in the treatment of benign prostatic hypertrophy. Some AARAs, such as terazosin, stimulate glycolysis and increase cellular adenosine triphosphate levels through activation of phosphoglycerate kinase 1 (PGK1), which has been suggested to be of therapeutic benefit in patients with Parkinson disease (PD). OBJECTIVE: This study aimed to determine whether exposure to PGK1-activating AARAs was associated with slower PD progression. METHODS: National Veterans Affairs administrative data were used to identify patients who initiated PD-related pharmacotherapy during 2000 to 2019 and were concurrently prescribed an AARA. Using a retrospective cohort design, the count of incident PD-related outcome events within 1 year of follow-up was contrasted between patients prescribed a PGK1-activating AARA versus tamsulosin (an AARA without PKG1 stimulation), using multivariable negative binomial regression. PD-related outcome events were identified using ICD codes indicating motor symptoms, nonmotor symptoms, and other potential complications as clinical markers for the progression of PD. RESULTS: A total of 127,142 patients initiated drug therapy for PD during the observation period, of whom 24,539 concurrently received an AARA. Incident PD-related events were observed significantly less often in patients receiving a PGK1 AARA (n = 14,571) than tamsulosin (n = 9968) (incidence rate ratio [IRR] 0.80 [95% CI 0.77-0.83]). These results remained significant after adjustment for confounding factors (IRR 0.85 [95% CI 0.81-0.88]) and in sensitivity analyses. CONCLUSION: Patients prescribed a PGK1-activating AARA experienced fewer PD-related outcome events than patients prescribed tamsulosin. These results may indicate a role for terazosin and other PGK1 activators in slowing disease progression of PD; however, randomized controlled trials are needed.

Bisphenol A exposure stimulates prostatic fibrosis via exosome-triggered epithelium changes.

Fibrosis is the pathological basis for the clinical progression of benign prostatic hyperplasia (BPH). Prostatic fibrosis is an important risk factor in patients with BPH who experience lower urinary tract symptoms. Bisphenol A (BPA) is an environmental endocrine disruptor (EED) that causes prostate defects. The effects of BPA on the prostate were investigated in this study using mouse and human prostate cell models. BPA-induced mouse prostatic fibrosis is characterized by collagen deposition and an increase in hydroxyproline concentration. Furthermore, BPA-exposed prostatic stromal fibroblasts exosomes promote the epithelial-mesenchymal transition of epithelial cells. High-throughput RNA sequencing and functional enrichment analyses show that substantially altered mRNAs, lncRNAs and circRNAs play roles in cellular interactions and the hypoxia-inducible factor-1 signaling pathway. The results showed that exosomes participated in the pro-fibrogenic effects of BPA on the prostate by mediating communication between stromal and epithelial cells and triggering epithelial changes.

Effects of Taraxaci Herba (Dandelion) on Testosterone Propionate-Induced Benign Prostatic Hyperplasia in Rats.

Benign prostatic hyperplasia (BPH) is the non-malignant enlargement of the prostate, associated with lower urinary tract symptoms (LUTSs). Taraxaci Herba (TH), commonly known as dandelion, has traditionally been utilized in East Asia to treat symptoms related to LUTSs. Based on this traditional use, our study aimed to explore the inhibitory effects of TH on BPH progression using a testosterone propionate-induced rat model. To induce BPH, male Sprague Dawley rats were castrated and injected subcutaneously with testosterone propionate (3 mg/kg/day) for 28 days. Concurrently, TH extract was administered orally at doses of 100 and 300 mg/kg/day throughout the four-week period of testosterone propionate injections. The TH extract significantly reduced both the absolute and relative weights of the prostate, along with histopathological changes in the gland. Moreover, it lowered serum levels of testosterone and dihydrotestosterone and reduced the expression of the androgen receptor in the prostate. Additionally, the TH extract modulated the protein expressions of Bax and Bcl-2, which are key regulators of apoptosis in prostate cells. Collectively, our findings suggest that TH inhibits BPH development partially by modulating androgen signaling and inducing apoptosis within the prostate.

Effect of methanol extract of Plectranthus esculentus N.E.Br tuber and its fractions on indices of benign prostatic hyperplasia in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Many ethnopharmacological properties (anti-tumor, etc.) have been credited to Plectranthus esculentus tuber but the scientific basis has not been established. AIM OF THE STUDY: To evaluate the effect of methanol extract of P. esculentus tuber (MEPET) (phase 1) and its fractions (phase 2) on benign prostatic hyperplasia (BPH) in rats. MATERIALS AND METHODS: The study was conducted in two phases. Phase 1, thirty-five male albino rats (6 weeks old) were divided into seven groups of five rats each: normal control (NC) received olive oil (subcutaneously) and water (orally); disease control (DC) received testosterone propionate (TP) (3 mg/kg) and water; test groups (1,2,3 and 4) received TP + MEPET at 100, 200, 400, 600 mg/kg respectively; positive control, received TP + finasteride (5 mg/70 kg). After 28 days, their relative prostate weights (RPW) and prostate specific antigen (PSA) were determined. Phase 2, thirty rats were divided into 6 groups of 5 rats each: NC received olive oil (subcutaneously daily) and dimethyl sulfoxide (DMSO) (orally); DC received TP (3 mg/kg), and DMSO; test group 1 received TP and aqueous fraction of MEPET (400 mg/kg); test group 2 received TP and methanol fraction of MEPET (400 mg/kg); test group 3 received TP, and ethyl acetate fraction of MEPET (400 mg/kg); positive control received TP and finasteride (5 mg/70 kg). After 28 days, their erythrocyte sedimentation rates, RPW, prostate levels of PSA, DHT, inflammatory, apoptotic markers and prostate histology were determined. RESULTS: Ethyl acetate fraction of MEPET modulated most of the parameters of BPH in the rats in a manner akin to finasteride as corroborated by prostate histology. CONCLUSIONS: EFPET could be useful in the treatment of BPH.

Zhuangyao Jianshen pill ameliorates testosterone-induced benign postatic hyperplasia in rats.

OBJECTIVE: To determine the therapeutic effects of the Zhuangyao Jianshen pill (, ZYJSP) against benign prostatic hyperplasia (BPH) and investigate the underlying mechanism. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into six groups: Control group, BPH model group, finasteride-treated group, ZYJSP low, medium and high dose groups. Except for the control group, 40 rats were castrated and injected with testosterone propionate (TP) for 28 consecutive day to induce BPH. Meanwhile, the corresponding drugs were administered by gavage. The prostate wet weight, prostate index (PI), and the histopathological changes in the prostate were measured as the basis for examining the efficacy of ZYJSP against BPH. Levels of the serum sex hormones, oxidative stress markers, inflammatory markers, renal function markers, growth factors, and Cyclin D1 expression in prostate were measured to characterize the therapeutic mechanism of ZYJSP against BPH. RESULTS: ZYJSP administration significantly reduced prostate wet weight and PI and ameliorated histological changes of the prostate in TP-treated castrated rats. TP markedly increased the levels of creatinine, blood urea nitrogen and growth factors in the serum as well as the expression of the Cyclin D1 in the prostate. Most of these markers were significantly decreased by ZYJSP. ZYJSP significantly restored the dysregulation of testosterone, estradiol, and dihydrotestosterone caused by TP. Furthermore, ZYJSP relieved TP-induced prostate injury and exhibited both anti-inflammatory and anti-oxidant activity by decreasing interleukin-6, interleukin-8, and malondialdehyde levels and increasing the activity of superoxide dismutase in the serum. CONCLUSION: These findings indicate that ZYJSP can effectively ameliorate BPH induced by TP in castrated rats, and the underlying mechanism might be related to regulating sex hormone balance, reducing oxidative stress, and inhibiting the inflammatory response.

Ageratum conyzoides Extract Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia via Inhibiting Proliferation, Inflammation of Prostates, and Induction of Apoptosis in Rats.

Ageratum conyzoides, an annual herbaceous plant that inhabits tropical and subtropical regions, has been traditionally used in Asia, Africa, and South America for phytotherapy to treat infectious and inflammatory conditions. However, the pharmacological effects of standardized ethanolic extract of Ageratum conyzoides (ACE) on benign prostatic hyperplasia (BPH) remain unexplored. The objective of this research is to examine the potential physiological impacts of ACE, a traditionally utilized remedy for inflammatory ailments, in a rat model with BPH induced by testosterone propionate (TP). Rats were subcutaneously administered TP (3 mg/kg) to induce BPH and concurrently orally administered ACE (20, 50, and 100 mg/kg) daily for 42 days. ACE markedly improved BPH characteristics, including prostate weight, prostate index, and epithelial thickness, while also suppressing androgens and related hormones. The findings were supported by a decrease in androgen receptor and downstream signals associated with BPH in the prostate tissues of the ACE groups. Furthermore, increased apoptotic signals were observed in the prostate tissue of the ACE groups, along with heightened detection of the apoptotic nucleus compared to the BPH alone group. These changes seen in the group that received finasteride were similar to those observed in this group. These findings suggest that ACE shows promise as an alternative phytotherapeutic agent for treating BPH.

Lysozyme gene treatment in testosterone induced benign prostate hyperplasia rat model and comparasion of its' effectiveness with botulinum toxin injection

ABSTRACT Objectives: To compare the effects and histopathological changes of botulinum neurotoxin type A and lysozyme gene injections into prostate tissue within a testosterone induced benign prostate hyperplasia rat model. Materials and Methods: 40 male Wistar rats were randomized into four Groups. Group-1: Control, Group-2: Testosterone replacement, Group-3: Testosterone+botulinum neurotoxin type A, Group-4: Testosterone+plazmid DNA/liposome complex. Results: Estimated prostate volume of the testosterone injected Groups were higher than the control (p <0.05). Actual prostate weight of the testosterone injected Groups was higher than the control Group (p <0.05). Testosterone undecanoate increased the prostate weight by 39%. Botulinum neurotoxin type A treatment led to an estimated prostate volume and actual prostate weights decreased up to 32.5% in rats leading to prostate apoptosis. Lysozyme gene treatment led to an estimated prostate volume and actual prostate weights decrease up to 38.7%. Conclusion: Lysozyme gene and botulinum neurotoxin type A treatments for prostate volume decreasing effect have been verified in the present study that could be anew modality of treatment in prostatic benign hyperplasia that needs to be verified in large randomized human experimental studies.

Estudio del D-004 sobre la defensa antioxidante endógena en ratas con hiperplasia prostática inducida por inyección de testosterona / Study of D-004 on the endogenous antioxidant defence in rats presenting with prostate hyperplasia induced by testosterone injection

La hiperplasia prostàtica benigna, enfermedad común en hombres mayores de 50 años de edad, se caracteriza por el crecimiento incontrolado de la glàndula prostàtica y la presencia de síntomas del tracto bajo urinario. El estrés oxidativo ha sido recientemente asociado con la causa de esta enfermedad. El D-004, extracto lipídico del fruto de la Roystonea regia, ha mostrado reducir la hiperplasia prostàtica inducida por testosterona en roedores y producir efectos antioxidantes in vitro e in vivo, pero sus efectos sobre las enzimas del sistema antioxidante endógeno no han sido estudiados. Este trabajo investigó los efectos del tratamiento oral con D-004, durante 14 días, sobre las enzimas superóxido dismutasa y catalasa en ratas con hiperplasia prostàtica inducida por testosterona. Los animales se distribuyeron en 4 grupos: un control negativo y tres inyectados con testosterona: uno tratado con el vehículo (control positivo) y dos con D-004 (400 y 800 mg/kg, respectivamente). Se determinó la capacidad antioxidante total del plasma y las actividades de las enzimas superóxido dismutasa y catalasa en eritocitos lisados y plasma, respectivamente. El tratamiento oral con D-004 (400 y 800 mg/kg) previno de modo marcado y significativo el agrandamiento de la próstata inducido con testosterona en ratas, y aumentó significativamente la capacidad antioxidante del plasma y la actividad de la catalasa, sin modificar la actividad de la superóxido dismutasa. Estos resultados sugieren que la actividad antioxidante del D-004 està relacionada, al menos parcialmente, con la estimulación de algunas enzimas del sistema antioxidante endógeno.

Benign prostatic hyperplasia, a common disease in men aged over 50 is characterized by uncontrolled growth of prostatic gland and the presence of low urinary tract symptoms. The oxidative stress has been recently associated with the disease cause. The D-004, a lipid extract from Roystonea regia, reduces the prostatic hyperplasia induced by testosterone in rodents and to produce in vitro and in vivo antioxidant effects nut its effects on endogenous antioxidant4e system enzymes haven't been studied. Present paper researched the effects of D-004 oral treatment over 14 days on dismutase and catalase superoxide enzymes in rats with prostatic hyperplasia induced by testosterone. Animals were randomized distributed into 4 groups: a negative control ant three-testosterone injected: one treated with the vehicle (positive control) and two with D-004 (400 and 800 mg/kg, respectively). The plasma total antioxidant ability was determined as well as the activity of catalase and dismutase superoxide enzymes in lysed erythrocyte and plasma, respectively. D-004 (400 and 800 mg/kg) oral treatment markedly and significantly prevented the prostate enlargement induced with testosterone in rats and increased very much the plasma antioxidant activity and of catalase, without modify the superoxide dismutase. These results suggest that D-004 antioxidant activity is partially related to stimulation of some enzymes of the endogenous antioxidant system.

Validación histológica de un posible modelo de hiperplasia nodular prostática inducido con enantato de testosterona (100mg/ml) / Histological assessment of a possible model of nodular prostatic hyperplasia induced with testosterone enantate (100 mg/ml)

Estudio preclínico realizado en la Universidad Médica de Cienfuegos, Cuba, entre junio y diciembre de 2003, con el objetivo de validar desde el punto de vista histológico un posible modelo de hiperplasia prostática. Se utilizaron 15 ratas Sprague Dawley machos de 21 días de edad. El grupo I no se castró ni recibió, tratamiento con testosterona, mientras que los grupos II y III se orquiectomizaron y se les administró testosterona (25 mg/ml) a 3mg/kg subcutánea por veintiún días y enantato de testosterona (100 mg/ml) a 14 mg/kg en dosis única, respectivamente. La observación de los cortes histológicos se realizó en diez campos de 40X. La administración de enantato de testosterona causó una disminución del número de acinos e incrementó el número de capas epiteliales celulares, las aproximaciones interglandulares, las glándulas dilatadas y la presencia de pseudopapilas; el estroma se hizo más laxo y escaso. Los cambios histológicos hiperplásicos en estos animales fueron superiores cuantitativa y cualitativamente a los producidos por la administración de testosterona durante veintiún días.

Hiperplasia prostática inducida con testosterona y con testosterona más 17 Beta-estradiol en ratas castradas / Testosterone and testosterone plus 17 beta-estradiol prostatic hyperplasia induced in castrated rats

La hiperplasia prostática benigna tiene una etiología aún desconocida, postulándose que el estradiol (E2) esté posiblemente implicado. El objetivo de este trabajo fue determinar la acción del E2 en la proliferación prostática inducida en ratas castradas. El diseño fue experimental aleatorizado en 3 grupos independientes (para 8 ratas) durante 4 semanas; el 1ro, control sin tratamiento; el 2do, castrado y tratado con enantato de testosterona (ET); y el 3ro, castrado y tratado con ET más hemisuccinato de 17 beta-estradiol. La valoración de la diferencia de los pesos prostáticos fue hecha mediante una prueba U; los hallazgos histológicos, con microscopía de luz. Verificamos un mayor incremento de los pesos prostáticos del 3er grupo con respecto al segundo, (estadísticamente en el límite de la significancia, P=0,05). De igual manera, histológicamente, el aumento de la secreción y la hiperplasia fue notoria en el 3er grupo respecto a los 2 primeros. concluimos que el E2 sinergiza la acción proliferativa de la testosterona sobre la próstata, involucrándosele posiblemente en la génesis de la hiperplasia prostática benigna.