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Effect of Ethanol Extract of Abrus precatorious Seed on Testosterone-Induced Benign Prostatic Hyperplasia in Adult Male Wistar Rats
... The prostate is a part of the male reproductive system which contributes to the formation of semen by producing alkaline fluid that maintains and nourishes sperm [1]. Benign prostatic hyperplasia (BPH) is the result of a gradual overgrowth of the prostate gland; a gland that lies at the base of the bladder and encircles the urethra [2]. ...
... Lepidium meyeni, Benincasa hispida Congn., Sphaeranthus indicus, Abrus precatorious, Urtica dioica and Vernonia amygdalina have been established to have inhibitory effect on 5-alpha reductase enzyme activity, an enzyme that converts androgen to DHT [2,13,14,15,16]. These plants have demonstrated ameliorative effect on testosterone-induced prostate hyperplasia by reducing relative prostate weight in treated animals [1,13,14,15]. Also protective effect of Echinops echinatus and Ganoderma lucidum extracts [16,17,18,19] on testosteroneinduced BPH have been reported. ...
ABSTRACT
Background: The most significant risk factor for developing benign prostatic hyperplasia (BPH) is an advanced age. As BPH and aberrant changes in reactive oxygen species become more common with ageing, oxygen species signalling may play an important role in the development and progression of this disease. In this study, we investigated the effect of Nigerian indigenous plant; Vernonia amygdalina (VA) on oxidative stress indices in BPH induced rats.
Methods: BPH was induced in male rats weighing 200-300 g by exogenous administration of testosterone and estradiol via subcutaneous injection at a dose of 400 μg/kg testosterone (T) and 80 μg/kg estradiol (E2) respectively. Thirty (30) rats were divided into five groups. One group was used as a normal control, and the other groups received subcutaneous injections of the hormones for 3 weeks to induce BPH. Groups I and II were treated with different doses of VA extract (50 and 100 mg kg–1 body weight respectively) and group III received finasteride (0.1 mg kg–1), all by gavages for forty-two days, while group IV was left untreated, group V served as normal control. After forty-two days of treatment with VA extract, the rats were anaesthetised by short contact with trichloromethane vapour. Blood was collected by cardiac puncture and the sera centrifuged and used for the determination of different biochemical indices. The liver and kidney were harvested and homogenised and used for the assays of oxidative activities.
Results: The activities of catalase (CAT) and superoxide dismutase (SOD) in the extract treated rats were significantly increased when compared the BPH control which had a significant reduction in the activities of these enzymes. The concentration of reduced glutathione (GSH) in the extract treated group significantly (P<0.05) increased while thiobarbituric acid reactive substance (TBARS) concentration decreased when compared to BPH control group.
Conclusion: Human prostate tissue is vulnerable to oxidative damage due to more rapid cell turnover. Therefore Vernonia amygdalina can be used to reduce oxidative stress which was implicated in the pathogenesis of BPH.
... Benign prostatic hyperplasia (BPH) is one of the most common conditions that affects geriatric men. It is characterized by an abnormal increase in the size and weight of the prostate gland [33]. In BPH, the prostate becomes larger, compressing the urethra while putting pressure on the bladder, which impedes normal urine output. ...
Benign prostatic hyperplasia (BPH) is one of the common disorders amongst the geriatric male population, affecting their quality of life. Since conventional drugs used for the treatment are sometimes accompanied by serious side effects, the search for alternative treatments remains urgent.
... of the exposure phase, BPH was induced by subcutaneous administration of testosterone propionate (Testost ® ) (3 mg/kg) for 28 days as previously described [41]. ...
Background
Benign prostatic hyperplasia (BPH) is a major health concern associated with lower urinary tract symptoms and sexual dysfunction in men. Recurrent inflammation, decreased apoptotic rate and oxidative stress are some of the theories that explain the pathophysiology of BPH. Common salt, a food additive, is known to cause systemic inflammation and redox imbalance, and may serve as a potential risk factor for BPH development or progression. This study examined the effect of common salt intake on the pathology of testosterone-induced BPH.
Methods
Forty male Wistar rats were randomly divided into four equal groups of 10: a control and three salt diet groups-low-salt diet (LSD), standard-salt diet (SSD) and high-salt diet (HSD). The rats were castrated, allowed to recuperate and placed on salt-free diet (control), 0.25% salt diet (LSD), 0.5% salt diet (SSD) and 1.25% salt diet (HSD) for 60 days ad libitum. On day 33, BPH was induced in all the rats with daily injections of testosterone propionate-Testost® (3 mg/kg body weight) for 28 days. The rats had overnight fast (12 h) on day 60 and were euthanized the following day in order to collect blood and prostate samples for biochemical, molecular and immunohistochemistry (IHC) analyses. Mean ± SD values were calculated for each group and compared for significant difference with ANOVA followed by post hoc test (Tukey HSD) at p < 0.05.
Results
This study recorded a substantially higher level of IL-6, IL-8 and COX-2 in salt diet groups and moderate IHC staining of COX-2 in HSD group. The prostatic level of IL-17, IL-1β, PGE2, relative prostate weight and serum PSA levels were not statistically different. The concentrations of IGF-1, TGF-β were similar in all the groups but there were multiple fold increase in Bcl-2 expression in salt diet groups-LSD (13.2), SSD (9.5) and HSD (7.9) and multiple fold decrease in VEGF expression in LSD (-6.3), SSD (-5.1) and HSD (-14.1) compared to control. Activity of superoxide dismutase (SOD) and concentration of nitric oxide rose in LSD and SSD groups, and SSD and HSD groups respectively. Activities of glutathione peroxidase and catalase, and concentration of NADPH and hydrogen peroxide were not significantly different. IHC showed positive immunostaining for iNOS expression in all the groups while histopathology revealed moderate to severe prostatic hyperplasia in salt diet groups.
Conclusions
These findings suggest that low, standard and high salt diets aggravated the pathology of testosterone-induced BPH in Wistar rats by promoting inflammation, oxidative stress, while suppressing apoptosis and angiogenesis.
... In the current study, MDA levels were shown to be significantly higher in the prostatic tissues of BPH-induced rats in comparison to control rats, while antioxidant enzymes such as superoxide dismutase (SOD), reduced glutathione (GSH), and catalase (CAT) activities were significantly lower. These findings in BPH animals are consistent with prior observations [23,99]. The results of this study revealed that BPHinduced rats treated with AgNPs-NIR, and finasteride therapies significantly reduced oxidative stress via decreased MDA levels and increased SOD and CAT activities. ...
Aims
In this study, we used a near-infrared laser (NIR) to increase the potency of silver nanoparticles (AgNPs) to develop a novel, less invasive, and simple photothermal therapy technique for benign prostate hyperplasia (BPH).
Materials and methods
The shape, particle size, and zeta-potential of polyvinylpyrrolidone coated-AgNPs (PVP-AgNPs) were determined using transmission electron microscopy (TEM), Zeta-potential, and Particle size analyzer (ELSZ). To induce BPH, thirty-six male Sprague-Dawley (SD) rats were given intramuscular (i.m) injections of testosterone propionate (TP) at 5 mg/kg body weight (b.w)/day suspended in 0.1 ml of olive oil for 14 days. Photothermal therapy with AgNPs-NIR for 14 days was carried out. Prostate size, prostate index (PI), dihydrotestosterone (DHT), prostate-specific antigen (PSA), gross, hepatic, and renal toxicity, as well as antioxidant activity, apoptosis, and angiogenesis markers in prostatic tissues were measured. Histological examinations of prostates and biocompatibility of NIR-AgNPs on vital organs were also performed.
Key findings
The aggregated spherical AgNPs with a mean size of 50–90 nm and a Zeta potential of −53.22 mV displayed high effectiveness in the NIR (532 nm–1 W) region by decreasing prostate size, PI, DHT, and PSA in BPH rats with no signs of gross, hepatic, or renal damage. As compared to alternative therapies, hyperthermia therapy increased antioxidant activities, induced apoptosis, inhibited angiogenesis, reduced histological alterations in the prostates of BPH rats, and improved biocompatibility of the vital organs.
Significance
The current study demonstrated the effectiveness of plasmonic AgNPs photothermal therapy in the treatment of BPH.
... Previous reports on phytotherapeutic management of BPH established the inhibitory effect of Lepidium meyeni extract [25] and protective effect of Echinops echinatus and Ganoderma lucidum extracts [20,21] on testosterone induced BPH. Benincasa hispida Congn., Sphaeranthus indicus, Abrus precatorious and Urtica dioica were reported to inhibit 5-alpha reductase enzyme activity [1,26] and these plants have demonstrated ameliorative effect on testosterone-induced prostate hyperplasia by reducing relative prostate weight in treated animals [1,22,23]. Seronoa repens also known as saw palmetto contains sterols and its inhibitory effect on 5-alpha reductase activity with attendant decrease in DHT production has been reported to be useful in the management of [27]. ...
Background: Benign Prostate hyperplasia (BPH) is a highly prevalent disease among older men and a substantial public health problem. We investigated leaf extract of Ocimum gratissimum (OG) effect on lipid prolife in BPH. Methods: BPH was induced in male rats weighing 200-300g through exogenous administration of testosterone and estradiol. Thirty (30) rats were divided into five groups. Four groups received subcutaneous injections of the two hormones and one group was used as a control with injections of hormones. Groups I to II were administered orally with different doses of extract and group III received standard drug, group IV was not treated and group V served as normal control. After Thirty-five days of treatment, the rats were sacrificed and blood collected through cardiac puncture for biochemical analysis. The prostate were harvested and weighed. Original Research Article Ugwu et al.; JAMPS, 17(3): 1-8, 2018; Article no.JAMPS.43113 2 Results: In rats treated with extract and standard drug a significant decrease in the size of the enlarged prostate was observed (P<0.05) when compared with the BPH control group. Weight gain was observed in rats treated with extract and finasteride. The level of cholesterol, LDL-C and VLDL-C were significantly reduced while HDL-C increased when compared to the BPH control. Conclusion: The significant reduction of cholesterol, LDL, VLDL-C and increase in HDL-C in the treated groups supported by decline in prostate weight suggest that the extract have the capacity of managing the lipid alterations caused by induction of BPH in rats.
Background
Benign prostatic hyperplasia (BPH) is a major health concern in men associated with lower urinary tract symptoms and sexual dysfunction. Recurrent inflammation, decreased apoptotic rate and oxidative stress are some of the theories that explain the pathophysiology of BPH. Common salt, a food additive, is known to cause systemic inflammation and redox imbalance, and may serve as potential risk factors for BPH development or progression. This study examined the effect of common salt intake on the pathophysiology of testosterone-induced BPH.
Methods
Forty male Wistar rats were randomly divided into four groups (10 in each group): the control group and three salt diet groups-low salt diet (LSD), standard salt diet (SSD) and high salt diet (HSD). The rats were castrated, allowed to recuperate and placed on salt free diet (control), 0.25% salt diet (LSD), 0.5% salt diet (SSD) and 1.25% salt diet (HSD) for 60 days ad libitum. On day 33, BPH was induced in all the rats with daily injection of testosterone propionate (Testost®) for 28 days. The rats had overnight (12 hours) on day 60 and euthanized the following day in order to collect blood and prostate samples for biochemical, molecular and immunohistochemistry (IHC) analyses. Mean ± SD values were calculated and compared for significant difference with t-test (control and salt diet groups) and one-way ANOVA (in between salt diet groups) at p < 0.05.
Results
There was a significant rise in prostatic levels of IL-6, IL-8 and COX-2 in salt diet groups and moderate IHC staining of COX-2 in HSD group. The prostatic level of IL-17, IL-1β, PGE2, relative prostate weight and serum PSA levels were not statistically different. The concentrations of IGF-1, TGF-β were similar in all the groups but there was fold increase in Bcl-2 expression in salt diet groups-LSD (13.2), SSD (9.5) and HSD (7.9) and fold decrease in VEGF expression in LSD (-6.3), SSD (-5.1) and HSD (-14.1). Activity of SOD and concentration of nitric oxide increased in LSD and SSD groups, and SSD and HSD groups respectively. Activities of glutathione peroxidase and catalase, and concentration of NADPH and hydrogen peroxide were not significantly different. IHC result showed positive immunostaining for iNOS expression in all the groups whereas histopathology revealed moderate to severe prostate hyperplasia in salt diet groups.
Conclusions
There is a relationship between dietary salt intake and risk testosterone-induced BPH in Wistar rats, possibly, by promoting inflammation, oxidative stress, and suppressing apoptosis. These results reveal that intake of dietary salt at low, standard and high quantity aggravated the pathophysiology of testosterone-induced BPH in Wistar rats by promoting inflammation, oxidative stress, and suppressing apoptosis.
Abrus precatorius L. (Fabaceae) is a woody legume plant that grows in tropical countries and is an invasive weed in other areas. Extracts of this plant have insecticidal properties against several arthropod groups including Coleoptera, Diptera, Hemiptera, Isoptera, Lepidoptera and Orthoptera. It also has inhibitory effects against other pests including fungal plant pathogens, parasitic protozoans and molluscs. Studies that have examined the efficacy of A. precatorius extracts against invertebrate pests found in the South Pacific region suggest that this plant may be a potential mean for controlling many important invasive agricultural pests. Harvest and usage of A. precatorius may serve a dual purpose to restrict weed growth whilst providing material to produce a botanically-derived insecticide.
The methanolic extract of the leaves of Abrus precatorius was evaluated for possible bronchodilator activity by using various in vivo and in vitro models in guinea pigs. Animal studies involved the use of histamine induced broncho-constriction in guinea pigs. These studies showed reduced activity at lower concentration but significant protection at higher doses. The extract offered a maximum degree of protection of 41.62% which was comparable to that of salbutamol 47.52%. The effect of the methanolic extract of the plant on isolated guinea pig ileum was studied to know the mechanism by which the extract exhibited muscle relaxant activity. The study showed the extract is effective against histamine and acetylcholine-induced contractions. The extract exhibited maximum relaxation effect against histamine and acetylcholine induced contraction at a concentration of 100mg/ml. The results revealed that the methanolic extract produced dose-dependent bronchodilator activity, thus justifying to some extent the traditional use of the plant Abrus precatorius in asthma.
Seeds of Abrus precatorius L., Fabaceae, are commonly used as purgative, emetic, aphrodisiac and in nervous disorder in traditional and folk medicines. In present study petroleum ether and ethanolic extracts of A. precatorius seeds are evaluated for reversal of androgen (testosterone by i.m route) induced alopecia in male albino wistar rats and compared to topical administration of standard antiandrogenic drug finasteride for 21 days. The results were reflected from visual observation and histological study of several skin sections via various parameters as anagen to telogen ratio and follicle density/mm area of skin surface. The animal of group 1 who were treated with only testosterone became alopecic on visual observation. Animals of Group 2, 3 and 4 who were treated with finasteride, petroleum ether and ethanolic extract of seed respectively topically along with testosterone (i.m) did not developed alopecia. To investigate the mechanism of observed activity, in vitro experiments were performed. Inhibition of 5α-reductase activity by extracts and finasteride suggest that they reversed androgen induced alopecia by inhibiting conversion of testosterone to dihydrotestosterone (potent androgen responsible for androgenic alopecia). So it may be concluded that petroleum ether and ethanolic extract of A. precatorius seed posses anti androgenic alopecia activity due to inhibition of 5α-reductase enzyme.
Reproductive toxicity studies are increasingly including assessments of sperm parameters including motility, morphology, and counts. While these assessments can provide valuable information for the determination of potential reproductive toxicity, the methods for conducting the assessments have not been well developed in all laboratories and are continually evolving. The use of different methods in different laboratories makes comparison of data among laboratories difficult. To address the differences in methods, a working group was convened to discuss methods currently in use, share data, and try to reach consensus about optimal methods for assessing sperm parameters in rats, rabbits, and dogs. This article presents the consensus report, as well as future research needs, with the hope that optimized common methods will aid in the detection of reproductive effects and enhance interlaboratory comparisons.
To determine effects of curcumin on N-methyl-N-nitrosourea (MNU) and saturated sodium chloride (s-NaCl)-induced gastric cancer in rats. Male Wistar rats were divided into 5 groups: control (CO), control supplemented with 200 mg/kg curcumin (CC), MNU + s-NaCl, MNU + s-NaCl supplemented with 200 mg/kg curcumin daily for the first 3 weeks (MNU + s-NaCl + C3W), and MNU + s-NaCl supplemented with curcumin for 20 weeks (MNU + s-NaCl + C20W). To induce stomach cancer, rats except for CO and CC were orally treated with 100 mg/kg MNU on day 0 and 14, and s-NaCl twice-a-week for the first 3 weeks. The experiment was finished and rats were sacrificed at the end of 20 weeks. Cancers were found in forestomachs of all rats in MNU + s-NaCl. The expressions of phosphorylated inhibitor kappaB alpha (phospho-IκBα), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and cyclin D1 significantly increased in MNU + s-NaCl compared with CO. Curcumin treatments for 3 and 20 weeks reduced the cancer incidence resulting in a decrease of phospho-IκBα expression in benign tumor-bearing rats compared with MNU + s-NaCl. Curcumin treatment for 20 weeks also decreased 8-OHdG expression in benign tumor-bearing rats compared with MNU + s-NaCl. Curcumin can attenuate cancer via a reduction of phospho-IκBα and 8-OHdG expressions, which may play a promising role in gastric carcinogenesis.
Background:
Benincasa hispida Cogn. has been used traditionally in India for the management of urinary disorders. The fruit of B hispida is used as a diuretic and the seeds have been reported to possess antiangiogenic effects in prostate cells.
Objective:
The aim of the present study was to examine the effect of petroleum ether extract, ethanolic extract, and B hispida seed oil on hyperplasia of the prostate induced by the subcutaneous administration of testosterone in rats.
Methods:
In vitro studies were performed to determine the 5α-reductase inhibitory potential of the extracts. The results of those studies paved the way for the pharmacologic screening of the extracts to assess their potential against testosterone-induced hyperplasia in rats. Nine groups containing 10 rats per group were created for this study. Hyperplasia was induced by administration of testosterone (3 mg/kg SC) for 14 days in all the groups except the vehicle-treated group. Simultaneous administration of petroleum ether extract (100 or 200 mg/kg PO), ethanolic extract (100 or 200 mg/kg PO), and B hispida seed oil (20 or 40 mg/kg PO) was conducted. A standard 5α-reductase inhibitor (ie, finasteride) was used as a positive control. The weight of the rats was recorded on day 0 (ie, day 1 of the study) and on day 14, and the influence of testosterone and test extracts on the weight of the rats was determined. On day 14, rats were euthanized; prostates were dissected out, and weighed. The rats' prostate/body weight (P/BW) ratio was then determined. Histologic examinations were performed on prostates from each group.
Results:
The petroleum ether extract as well as B hispida seed oil exhibited inhibition of 5α-reductase activity in in vitro studies. Ethanolic extract did not exhibit significant inhibitory potential in vitro. Further in vivo study found that testosterone treatment significantly increased the rats' P/BW ratio in all the groups except the vehicle-treated rats, and this increase in weight was significantly inhibited in rats administered petroleum ether extract (100 and 200 mg/kg PO) and B hispida seed oil (20 and 40 mg/kg PO). Ethanolic extract did not exhibit any significant activity.
Conclusions:
Petroleum ether extract and B hispida seed oil inhibited testosterone-induced hyperplasia of the prostate in these rats. Further studies are needed to evaluate its effect in humans with benign prostatic hyperplasia.
Estrogens and androgens have both been implicated as causes of benign prostatic hyperplasia (BPH). Although epidemiological data on an association between serum androgen concentrations and BPH are inconsistent, it is generally accepted that androgens play a permissive role in BPH pathogenesis. In clinical practice, inhibitors of 5α-reductase (which converts testosterone to the more potent androgen dihydrotestosterone) have proven effective in the management of BPH, confirming an essential role for androgens in BPH pathophysiology. To date, multiple lines of evidence support a role for estrogens in BPH pathogenesis. Studies of the two estrogen receptor (ER) subtypes have shed light on their differential functions in the human prostate; ERα and ERβ have proliferative and antiproliferative effects on prostate cells, respectively. Effects of estrogens on the prostate are associated with multiple mechanisms including apoptosis, aromatase expression and paracrine regulation via prostaglandin E2. Selective estrogen receptor modulators or other agents that can influence intraprostatic estrogen levels might conceivably be potential therapeutic targets for the treatment of BPH.
This study examined the inhibitory effects of a methanol extract of Abrus precatorius seeds on the motility of washed human spermatozoa. The extract caused a concentration-related impairment of percentage sperm motility; with the EC50 concentration being 2.29 mg/ml. This effect on motility was essentially irreversible. With the highest concentration tested (20.0 mg/ml), the onset of the antimotility action was almost immediate. In addition, this concentration impaired the functional integrity of the plasma membrane (hypoosmotic swelling test) and viability (nigrosin-eosin stain) of spermatozoa. In contrast, with a lower concentration (5.0 mg/ml), such effects were not evident. It is concluded that at the lower concentrations the antimotility action may result from a rise in intracellular calcium (not via influx) and/or a decline in cAMP content and/or enhanced generation of a reactive oxygen species.
The understanding of estrogen's function in the male reproductive tract is limited, and estrogen receptor (ER) localization in the reproductive tract of the adult male rat has not been described. In the present study, ERalpha was localized by immunohistochemistry using ER21 antibody, which recognizes only ERalpha. Strongest immunoreactivity was seen in epithelia of ductuli efferentes and the initial segment of the epididymis. Nuclei of both ciliated and nonciliated cells were positive. The epithelium of the rete testis, and caput, corpus, and cauda epididymides stained less intensely for ERalpha. The vas deferens epithelium was ERalpha-negative. Stromal tissue in the excurrent ducts was also ERalpha-positive. Using 3H-estradiol autoradiography, specific binding of estradiol was seen in nuclei of ductuli efferentes. Estrogen receptor alpha mRNA expression was greatly enhanced in ductuli efferentes compared to other regions of the male tract and was 3.5x greater than in the uterus. For comparison, the presence of ERalpha was determined using reverse transcription-polymerase chain reaction (RT-PCR) amplification. Estrogen receptor beta mRNA was expressed throughout the male tract and in the prostate. These results indicate that all organs in the male excurrent ductal system of the rat express ERalpha and are potential targets of estrogen. However, the ductuli efferentes are the site of the most intense ERalpha expression. The role of ERbeta remains to be determined, but its expression appears ubiguitous in the male tract.
Androgens are essential for stimulating normal development, growth and secretory activities of the prostate whereas oestrogens are generally regarded as inhibitors of growth. Evidence for the local synthesis of oestrogens includes the detection of aromatase mRNA and protein in the stroma of human non-malignant tissues and in malignant tissue, where it is detected in epithelial tumour cells. As well, aromatase activity was measured by biochemical assay and protein was detected in prostatic non-malignant and tumour cell lines. Taken together with the identification of direct oestrogenic actions on the prostate, these results suggest that alterations in local oestrogen synthesis may have significant consequences in malignancy of these organs. Genetically modified mouse models were studied in order to evaluate the action of oestrogens alone or in combination with androgens on the prostate gland. Hypogonadal (hpg) mice are deficient in gonadotrophins and androgens but showed direct proliferative responses to oestradiol. The responses were characterised by discrete lobe-specific changes including smooth-muscle regression, fibroblast proliferation, inflammation, and basal epithelial cell proliferation and metaplasia. The aromatase knockout (ArKO) mouse, deficient in oestrogens due to a non-functional aromatase enzyme, developed prostatic hyperplasia during the lifelong exposure to elevated androgens, however, no malignant changes were detected in the prostate at any time. In contrast, combined androgen and oestrogen treatment has been shown to induce prostatic dysplasia and adenocarcinoma. These results demonstrate that malignant changes to the prostate gland are dependent upon both androgenic and oestrogenic responses and that neither hormone alone is sufficient to evoke aberrant patterns of growth, resulting in malignancy.
The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5 g/kg body wt. A positive control group received Finasteride (0.6 mg/kg body wt.). After treatment, the animals were sacrificed, and the ventral prostate was extracted, and weighed. HPLC was used to determine the presence of glucosinolates in Red Maca. The prostate weight diminished in a dose-dependent fashion in rats treated with Red Maca. The effect of Red Maca was better than that observed with Finasteride. Finasteride, but not Red Maca, reduced seminal vesicles weight. Analysis of the HPLC indicated the presence of benzyl glucosinolate (Glucotropaeolin) with a content of 0.639%. Serum testosterone levels were not affected by Red Maca. Moreover, serum testosterone levels were not related to prostate or seminal vesicles weight in rats treated with vehicle and Red Maca. In conclusion, Red Maca administered orally in rats seems to exert an inhibitory effect at a level post DHT conversion, on the BPH-induced experimentally, although a direct measure of reductase action would still be required.
Prostate cancer is one of the most complex and enigmatic oncologic problems in medicine. It is highly prevalent, particularly in elderly males. Unfortunately, its generally protracted and variable clinical course and high association with treatment-related morbidity raise serious questions about the ideal treatment strategy for the individual patient. 5 alpha-reductase (5AR) inhibitors have a dramatic effect on benign prostatic disease with low toxicity. Thus, there is much interest in the potential role of 5AR inhibitors in the prevention and treatment of prostate cancer. Finasteride is the only agent that has been shown in a randomized clinical trial to decrease the risk of prostate cancer with a reduction of almost 25%. Additionally, a recent analysis of the Prostate Cancer Prevention Trial (PCPT) has found that finasteride improves the performance characteristics of prostate-specific antigen (PSA) blood test as a screening tool for prostate cancer, for both cancer detection as well as for detection of high risk disease. Finally, 5AR inhibitors have been studied as a component of multimodal therapy for all stages of prostate cancer, with the goal of improving oncologic outcomes while avoiding the toxicity of medical and surgical castration.
Prostate cancer (PC) and benign prostate hyperplasia (BPH) constitute many of the health concerns of males around the world. Prostate cancer is the major cause of death after lung cancer in men. Benign prostate hyperplasia affects most males above 40 years of age. A variety of factors, chiefly age, genetics and lifestyle, have been linked to the development of PC and BPH. The metabolic syndrome describes a chain of chronic disorders that are inter-related in aetiology, and result from unhealthy lifestyles, often due to an affluent economy. The eating of processed foods and a sedentary lifestyle apparently are status symbols among the middle and upper classes in sub-Saharan Africa. These have resulted in a surge in the disease burden of sub-Saharan Africa. This paper looks at the aetiology and prevalence of the metabolic syndrome and prostatic diseases, especially in sub-Saharan Africa. Evidence from the available literature shows that prostate disorders may be related to the metabolic syndrome. There is a likelihood that if sub-Saharan Africans keep copying the lifestyles of the developed world, especially in the direction of the nature of food items consumed, then the rising prevalence of diseases of the metabolic syndrome and the attendant prostate disorders may become very formidable healthcare "twin" problems for the region.
Oestrogens have been implicated as a cause of benign prostatic hyperplasia (BPH). Previous animal studies led to the hypothesis that oestrogens can stimulate prostate growth, resulting in hyperplasia of the gland. In humans, the precise role of oestrogens in BPH pathogenesis is currently unclear. We investigated the direct effects of oestradiol on the proliferation of BPH-derived prostate cells in culture. Oestradiol (10(-7) and 10(-6) M) moderately increased the proliferation of stromal cells in culture; this stimulation was antagonised by anti-oestrogen ICI 182 780, indicating an oestrogen receptor (ER)-mediated mechanism. By contrast, oestradiol had no effects on the proliferation of epithelial cells in culture. Parameters that can determine the response of stromal cells to oestrogens, including expression of the two ER subtypes and aromatase activity, were investigated. ER beta expression in stromal cells in culture was demonstrated by immunohistochemistry and western blot analysis, and was confirmed by semi-quantitative RT-PCR showing higher expression of ER beta than ER alpha mRNA in stromal cells. Aromatase, the enzyme that converts androgen precursors to oestrogens, was also examined. Aromatase mRNA and activity were detected in stromal, but not epithelial cells in culture, suggesting a mechanism whereby oestrogen concentrations can be regulated in the BPH stroma. Taken together, these findings support the hypothesis that oestrogens play a role in the pathogenesis of BPH, a disease characterised predominantly by stromal overgrowth.
Although benign prostatic hyperplasia (BPH) is one of the most common disease processes affecting the aging man, surprisingly little is known about its pathophysiology [1]. Despite intense research efforts in the past four to five decades to find the underlying cause of prostatic growth in older men, cause and effect relationships have not been established. Previously held notions that the clinical symptoms of BPH (prostatism) are simply due to a mass-related increase in urethral resistance are too simplistic. It is now clear that a significant portion of the symptoms are caused by obstruction-induced detrusor dysfunction. Moreover, obstruction may induce a variety of neural alterations in the bladder and prostate that contribute to symptomatology. Undoubtedly, the constellation of cellular pathologies that give rise to the symptoms of BPH will be far more complex than we currently realize. Only by revealing these complexities, however, will we be able to successfully design alternative strategies to treat, and possibly prevent, BPH.
Recently published data suggest that clinical benign prostatic hyperplasia (BPH), which is hallmarked by the occurrence of moderate-to-severe lower urinary tract symptoms (LUTS), occurs in about one quarter of men in their 50s, one third of men in their 60s, and about half of all men 80 years or older. Although effective treatments for LUTS/BPH are available, this condition often occurs in the context of common, age-related comorbidities such as cardiovascular disease, hypertension, and erectile dysfunction. Alpha(1)-selective adrenergic receptor (alpha(1)-AR) antagonists (eg, alfuzosin, doxazosin, tamsulosin, terazosin) remain the cornerstone of therapy for LUTS/BPH. In addition, 5-alpha-reductase inhibitors (ie, dutasteride, finasteride) have been associated with improvements in LUTS/BPH in men with larger prostates, especially when used in combination with alpha(1)-AR antagonists. Although all these drugs have been shown to be beneficial for the treatment of BPH, there are differences in side-effect profiles. When selecting an appropriate course of therapy, these side effects and any impact they may have on existing comorbid conditions must be considered.
Estrogens and estrogen receptors (ESRs) have been implicated in the stimulation of aberrant prostate growth and the development of prostate diseases. The aim of the present study was to investigate four single nucleotide polymorphisms (SNPs) of the ESR2 gene in order to examine whether ESR2 is a susceptibility gene for benign prostatic hyperplasia (BPH). In order to evaluate whether an association exists between ESR2 and BPH risk, four polymorphisms [rs4986938 (intron), rs17766755 (intron), rs12435857 (intron) and rs1256049 (Val328Val)] of the ESR2 gene were genotyped by direct sequencing. A total of 94 patients with BPH and 79 control subjects were examined. SNPStats and Haploview version 4.2 we used for the genetic analysis. Multiple logistic regression models (codominant1, codominant2, dominant, recessive and log‑additive) were produced in order to obtain the odds ratio, 95% confidence interval and P‑value. Three SNPs (rs4986938, rs17766755 and rs12435857) showed significant associations with BPH (rs4986938, P=0.015 in log‑additive model; rs17766755, P=0.033 in codominant1 model, P=0.019 in dominant model and P=0.020 in log‑additive model; rs12435857, P=0.023 in dominant model and P=0.011 in log‑additive model). The minor alleles of these SNPs increased the risk of BPH, and the AAC haplotype showed significant association with BPH (χ2=6.34, P=0.0118). These data suggest that the ESR2 gene may be associated with susceptibility to BPH.
The present study was designed to evaluate the contraceptive and toxicologic effects of methanolic extract (70%) of the seeds of Abrus precatorius (L.) (Fabaceae) in adult male mice. The body and organ weights, spermiogram, cauda epididymal biochemical indices, toxicological profile and fertility rate have been recorded. Treatment caused a significant decrease in caudal sperm motility, count and viability. There was a complete suppression of fertility at 40 mg/kg dose level. No significant changes were observed in caudal parameters like ATPase and protein except sialic acid levels. No significant alterations in haematological indices like haemoglobin, blood cell counts (RBC, WBC) or serum transaminases were observed. Contrarily, serum androgens reduced markedly. The extract thus exhibited contraceptive effect at higher dose and reversibility was observed after 90 days. The results suggest that the extract induces reversible antifertility effect.
Decades-old beliefs regarding androgens and prostate cancer (PCa) have undergone dramatic shifts in light of modern evidence and new theoretical constructs, but considerable confusion remains on this topic, particularly with regard to the use of testosterone therapy in men with any history of PCa.
To review current literature regarding the relationship of serum testosterone on PCa and in particular the effect of testosterone therapy on PCa progression and recurrence.
A Medline search was conducted to identify all original and review articles assessing the effect of androgens on the prostate and the use of testosterone in men with a history of treated and untreated PCa.
Contrary to traditional teaching, high endogenous serum testosterone does not increase the risk of developing PCa, and low serum testosterone does not protect against PCa. Although limited in size and duration, current studies similarly fail to indicate any increased risk of PCa in men receiving testosterone therapy. These results indicate a finite ability of androgens to stimulate PCa growth (the saturation model). A majority of studies demonstrate an association between low serum testosterone and poor prognostic features of PCa, including high-grade disease, advanced pathologic stage, and increased risk of biochemical recurrence following radical prostatectomy. The prostate-specific antigen-to-testosterone ratio predicted PCa risk in several biopsy studies. Multiple reports of testosterone therapy in men after treatment for localized PCa have shown low or absent recurrence rates. Some men with untreated PCa have received testosterone therapy without evidence for PCa progression.
The long-held belief that PCa risk is related to high serum androgen concentrations can no longer be supported. Current evidence indicates that maximal androgen-stimulated PCa growth is achieved at relatively low serum testosterone concentrations. It may therefore be reasonable to consider testosterone therapy in selected men with PCa and symptomatic hypogonadism.
Many men who reach average life expectancy will experience benign prostatic hyperplasia (BPH) or prostate cancer and together these conditions account for a considerable amount of ill-health and distress for men and their partners. Although there is considerable overlap across BPH and prostate cancer in symptom and risk profiles, management approaches are very different for each condition and appropriate diagnostic evaluation is therefore crucial to achieve the best possible outcome. The primary care physician should play a vital role in the diagnosis, management and appropriate referral of men with prostate disease with the ultimate goals being (1) early detection of prostate cancer and (2) effective treatment of benign prostate disease to manage symptoms and reduce the risk of progression.In prostate cancer, although there is debate over the implementation of systematic prostate-specific antigen (PSA) screening and appropriate thresholds, the use of PSA screening in conjunction with digital rectal examination (DRE) may aid earlier detection. The challenge is now to better determine which men are likely to develop aggressive disease so that overtreatment can be avoided. Results of large trials of systematic PSA screening are eagerly anticipated.In BPH, a major challenge is to identify men with bothersome lower urinary tract symptoms. Improved communication, education of patients, and the use of tools such as the International Prostate Symptom Score (IPSS) may help detect men who need treatment. Treatment selection should be driven by an understanding of the risks of disease progression, the impact of the disease on the patient's quality of life, and by the patient's own treatment preferences.Ultimately, we must empower our patients to make informed decisions about their diagnostic and treatment options through open dialogue and provision of appropriate information and education.
This study demonstrates 5α-reductase inhibitory activity of certain herbs useful in the management of androgenic disorders. Ganoderma lucidum (Curtis) P. Karst (GL), Urtica dioica Linn. (UD), Caesalpinia bonducella Fleming. (CB), Tribulus terrestris Linn. (TT), Pedalium murex Linn. (PM), Sphaeranthus indicus Linn. (SI), Cuscuta reflexa Roxb. (CR), Citrullus colocynthis Schrad. (CC), Benincasa hispida Cogn. (BH), Phyllanthus niruri Linn. (PN) and Echinops echinatus Linn. (EE) were included in the study. Petroleum ether, ethanol and aqueous extracts of these herbs were tested for their 5α-reductase inhibitory activity against the standard 5α-reductase inhibitor, finasteride. A biochemical method to determine the activity of 5α-reductase was used to evaluate the inhibition of different extracts to the enzyme. The optical density (OD) value of each sample was measured continuously with ultraviolet spectrophotometer for the reason that the substrate NADPH has a specific absorbance at 340 nm. As the enzyme 5α-reductase uses NADPH as a substrate, so in the presence of 5α-reductase inhibitor, the NADPH concentration will increase with the function of time. This method thus implicates the activity of 5α-reductase. The method proved to be extremely useful to screen the herbs for their 5α-reductase inhibitory potential. GL, UD, BH, SI and CR came out to be promising candidates for further exploring their antiandrogenic properties.
To evaluate the antifertility effect of crude mixture of A. precatorius seeds at the dose level of 50 mg/kg body weight in adult male rats, after oral administration to male rats for 40 days, the rats were sacrificed and hormonal profiles, serum biochemistry, sperm count and histological changes were recorded. A sharp decrease in the serum levels of testosterone (0.70 ± 0.17 ng/ml), FSH (0.70 ± 0.22 lU/L), and LH (0.87 ± 0.35 IU/L) was detected compared to control (FSH, LH and testosterone levels 0.93 ± 0.15 ng/ml, 0.76 ± 0.28 IU/L, 1.44 ± .011 IU/L, respectively). A significant reduction of epididymal sperm count (2.34 million/mL) was noted in treated rats as compared to control group (7.87 million/mL). Histology of testes showed marked atrophy of the testes, which was characterized by disruption of the seminiferous epithelium and atrophy of the Leydig cells. Crude mixture of A. precatorius seed has a negative impact on male reproductive functions. It might be suggested that crude mixture of A. precatorius seeds might have antifertility property for male rats.
The present study investigated the effects of stinging nettle (Urtica dioica L.) (UD) on benign prostatic hyperplasia (BPH) induced by testosterone. In vitro studies were conducted to assess the 5α-reductase inhibitory potential of UD. Two biochemical markers viz., β-sitosterol and scopoletin, were isolated and characterised in the extracts utilising High-performance thin layer chromatographic, FTIR, NMR and overlain UV spectral studies. Hyperplasia was induced in rats by subcutaneous administration of testosterone (3 mg kg(-1) s.c.) for 28 days in all the groups except the vehicle-treated group. Simultaneous administration of petroleum ether and ethanolic extracts (10, 20 and 50 mg kg(-1) p.o.) and isolated β-sitosterol (10 and 20 mg kg(-1) p.o.) was undertaken. Finasteride was used as a positive control (1 mg kg(-1) p.o.). Measurement of prostate/body weight ratio, weekly urine output and serum testosterone levels, prostate-specific antigen levels (on day 28) and histological examinations carried out on prostates from each group led us to conclude that UD can be used as an effective drug for the management of BPH.
Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology. While the precise molecular etiology remains unclear, sex steroids have been implicated in the development and maintenance of BPH. Sufficient data exists linking androgens and androgen receptor pathways to BPH and use of androgen reducing compounds, such as 5α-reductase inhibitors which block the conversion of testosterone into dihydrotestosterone, are a component of the standard of care for men with LUTS attributed to an enlarged prostate. However, BPH is a multifactorial disease and not all men respond well to currently available treatments, suggesting factors other than androgens are involved. Testosterone, the primary circulating androgen in men, can also be metabolized via CYP19/aromatase into the potent estrogen, estradiol-17β. The prostate is an estrogen target tissue and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of endogenous and exogenous estrogens in directly affecting prostate growth and differentiation in the context of BPH is an understudied area. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation signifying potential roles in BPH. Recent research has demonstrated that estrogen receptor signaling pathways may be important in the development and maintenance of BPH and LUTS; however, new models are needed to genetically dissect estrogen regulated molecular mechanisms involved in BPH. More work is needed to identify estrogens and associated signaling pathways in BPH in order to target BPH with dietary and therapeutic SERMs.
The present study reports the attenuating effect of Sphaeranthus indicus extracts (SI) on prostatic hyperplasia induced by testosterone in albino rats. In vitro studies were conducted to assess the 5α-reductase inhibitory potential of the petroleum ether, ethanolic and aqueous extracts of SI. A biochemical marker, β-sitosterol, was isolated and extracts were characterized utilizing HPTLC. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts and isolated β-sitosterol for a period of 28 days. The weight of the rats, the urine output, serum testosterone concentrations and prostate-specific antigen (PSA) levels were recorded. The prostate/body weight ratio (P/BW) was calculated and histological studies were performed to observe the changes in the histoarchitecture of the prostate. Finasteride was used as a positive control (1 mg/kg p.o.). Sphaeranthus indicus extracts attenuated the increase in the P/BW ratio induced by testosterone in the treated groups. The petroleum ether extract exhibited the best activity, although the ethanol and aqueous extracts also exhibited significant activity. Urine output was also improved significantly, demonstrating the clinical implications of the study. Histological studies, testosterone levels which were measured weekly and PSA levels measured at the end of the study also support claims for the potential use of Sphaeranthus indicus in the treatment of prostatic hyperplasia.
Little is known about midlife serum levels of dihydrotestosterone and other androgens before the onset of clinical benign prostatic hyperplasia in community dwelling older men.
We measured sex steroid hormones between 1984 and 1987 in the Rancho Bernardo Study. Between 1992 and 1996 surviving participants were evaluated for benign prostatic hyperplasia at followup clinic visits. Benign prostatic hyperplasia was defined as a history of noncancer prostate surgery or a medical diagnosis of benign prostatic hyperplasia. Regression modeling was used to examine associations of serum hormone measures with benign prostatic hyperplasia.
In 340 surviving participants with complete data available and no history of prostate cancer or benign prostatic hyperplasia at baseline mean +/- SD age was 64 +/- 9 years and mean followup was 8.4 +/- 0.8 years. Men who reported benign prostatic hyperplasia during followup were older at baseline than those who did not (p <0.001). Higher baseline serum dihydrotestosterone was associated with an increased risk of benign prostatic hyperplasia. The OR for the second, third and fourth quartiles of dihydrotestosterone was 1.83 (95% CI 0.96-3.47), 1.50 (0.79-2.85) and 2.75 (1.46-5.19), respectively (p trend = 0.02). A higher testosterone-to-dihydrotestosterone ratio was associated with a 42% decreased risk of benign prostatic hyperplasia when comparing the top 3 quartiles to the first quartile (OR 0.58, 95% CI 0.35-0.97, p = 0.04). Higher dehydroepiandrosterone was associated with an increased benign prostatic hyperplasia risk (p = 0.05).
Community dwelling men show a stepwise increase in benign prostatic hyperplasia risk with higher midlife serum dihydrotestosterone. These data justify investigations of 5alpha-reductase inhibitors for primary prevention of benign prostatic hyperplasia.
Numerous plants have proven to improve uncontrolled growth of the prostate gland and improve urinary tract symptoms associated with benign prostatic hyperplasia. Major components of those plants were lauric acid and myristic acid. Our study investigated whether lauric acid or myristic acid prevent testosterone induced prostatic hyperplasia in rats. Rats were divided into negative control and testosterone induced prostatic hyperplasia rats (positive control, low dose lauric acid treated, high dose lauric acid treated, low dose of myristic acid treated, high dose of myristic acid treated, finasteride treated). Testosterone and drug treatment were carried out for 14 days. Body weights were recorded before and after treatment. On 15th day, rats were sacrificed, prostates were weighed and histopathological studies were carried out. Lauric acid/myristic acid treatment showed significant inhibition of prostate enlargement and protection of histoarchitecture of prostate when compared with positive control group. In conclusion, the study showed that lauric acid/myristic acid reduced the increase of both prostate weight and prostate weight:body weight ratio, markers of testosterone induced prostatic hyperplasia in rats.
Dose-dependent degenerative changes in the testicular weights, sperm count, later stages of spermatogenesis and Leydig cells are observed in testis of rats treated with steroidal fraction of seeds of A. precatorius. These are correlated with the dose-dependent decrease in the enzyme activity of 3 alpha, 3 beta, 17 beta-hydroxysteroid dehydrogenases, glucose-6-phosphate dehydrogenase, sorbitol dehydrogenase and leucine aminopeptidase. The steroidal fraction may also exert its influence indirectly at the pituitary level by a feedback mechanism, leading to decrease in production and release of testosterone which results in significant alterations in the testis.
Although the presence of the testes is an absolutely necessary prerequisite for benign prostatic hyperplasia (BPH) to occur, the role of androgens in the cause of BPH is still controversial. There are increasing signs for a decisive role of estrogens in that connection. We treated castrated beagle dogs of known age with androstenedione (an androgen that can be aromatized) and with the aromatase inhibitor 4-hydroxyandrostendione. Six or 9 months of treatment with androstenedione resulted in a BPH characterized by typical androgenic effects--ie, hyperplasia and hypertrophy of the epithelium--and by typical estrogenic effects--, stimulation of the stroma, especially of the smooth muscles, and cystic enlargement of the tubules. These estrogen-related effects could be clearly antagonized by the simultaneous treatment with the aromatase inhibitor 4-hydroxyandrostenedione. The hyperplastic effects on the epithelium were also partly antagonized by the aromatase inhibitor. Our preliminary results further strengthen the effectiveness of aromatase inhibitors as an alternative treatment of human BPH, which is thought to be predominantly a stromal disease.
[3H]Rauwolscine ([3H]Ra), a selective ligand for the alpha 2 adrenergic receptor, was used to identify and characterize alpha 2 adrenergic receptors in prostate glands of men with benign prostatic hyperplasia. Specific binding of [3H]Ra to prostatic tissue homogenates was rapid and readily reversible by addition of excess unlabelled phentolamine. Scatchard analysis of saturation experiments demonstrates a single, saturable class of high affinity binding sites (Bmax = 0.31 +/- 0.04 fmol./microgram. DNA, Kd = 0.9 +/- 0.11 nM.). The relative potency of alpha adrenergic drugs (clonidine, alpha-methylnorepinephrine and prazosin) in competing for [3H]Ra binding sites was consistent with the order predicted for an alpha 2 subtype. The role of alpha 2 adrenergic receptors in normal prostatic function and in men with bladder outlet obstruction secondary to BPH requires further investigation.
The alpha-1 adrenergic innervation of the human prostate has been studied using radioligand receptor binding methods and in vitro contractile experiments. The density of alpha-1 adrenergic binding sites is of the same order of magnitude as alpha-2 adrenergic and muscarinic-cholinergic (MCh) receptors in the human prostate adenoma. The contractile response of human prostate adenomas to selective alpha-1, alpha-2, and MCh agonists indicated that smooth muscle contraction of the human prostate is mediated by alpha-1 adrenoceptors. The selective affinities of terazosin for alpha-1 and alpha-2 binding sites were determined using competitive displacement assays. Terazosin was shown to have a four hundred-fold greater affinity for alpha-1 binding sites. The concentration of terazosin-inhibiting phenylephrine-induced contractions suggested that terazosin inhibits prostate smooth muscle contraction via alpha-1 adrenoceptors.
Physiologic surges of serum androgen, estrogen and progesterone normally occur in both rat and human males during the neonatal periods. The effect of these hormone surges on the sex accessory tissues is not known. This study demonstrates that neonatal dihydrotestosterone, 17 beta-estradiol, or progesterone can permanently alter the androgen sensitivity of adult rat sex accessory tissues. Neonatal dihydrotestosterone or progesterone can permanently increase the androgen sensitivity of the adult prostate above normal while neonatal estradiol permanently decreases adult prostate androgen sensitivity below normal. The results of this preliminary study suggest that normally occurring neonatal hormone surges may permanently mark, or imprint, the prostate and determine its future growth in adulthood.
We determined the occurrence of and risk factors for acute urinary retention in the community setting.
A cohort of 2,115 men 40 to 79 years old was randomly selected from an enumeration of the Olmsted County, Minnesota population (55% response rate). Participants completed a previously validated baseline questionnaire that assessed symptom severity, and voided into a portable urometer to measure peak urinary flow rates. A 25% random subsample underwent transrectal sonographic imaging of the prostate to determine prostate volume. Followup was performed through a retrospective review of community medical records to determine the occurrence of acute urinary retention in the subsequent 4 years.
During the 8,344 person-years of followup 57 men had a first episode of acute urinary retention (incidence 6.8/1,000 person-years, 95% confidence interval [CI] 5.2, 8.9). Among men with no to mild symptoms (American Urological Association symptom index score 7 or less) the incidence of acute urinary retention increased from 2.6/1,000 person-years among men 40 to 49 years old to 9.3/1,000 person-years among men 70 to 79 years old. By contrast, rates increased from 3.0/1,000 person-years for men 40 to 49 years old to 34.7/1,000 person-years among men 70 to 79 years old among men with moderate to severe symptoms (American Urological Association symptom index score greater than 7). Men with depressed peak urinary flow rate (less than 12 ml. per second) were at 4 times the risk of acute urinary retention compared with men with urinary flow rates greater than 12 ml. per second (95% CI 2.3, 6.6). Men with an enlarged prostate (greater than 30 ml.) experienced a 3-fold increase in risk (95% CI 1.0, 9.0, p = 0.04).
Lower urinary tract symptoms, depressed peak urinary flow rates, enlarged prostates and older age are associated with an increased risk of acute urinary retention in community dwelling men. These findings may help to identify men at increased risk of acute urinary retention in whom closer evaluation may be warranted.
We report on a symptomatic anterior intraurethral prostatic cyst in a 46-year-old man without clinical evidence of benign prostatic hyperplasia. The anterior location of this cyst makes it unique to all previously reported cases of prostatic cysts which are located posteriorly. Transurethral resection of the cyst with limited resection of the anterior prostatic tissue at the base of the cyst was performed with successful resolution of voiding symptoms. In the absence of lateral lobe hypertrophy, standard transurethral resection of the prostate should be avoided to ensure preservation of erectile and ejaculatory function.
To investigate the effects of the phytotherapeutic agent, Permixon(R), on primary cultures of fibroblast and epithelial cells from the prostate, epididymis, testes, kidney, skin and breast and to determine the selectivity and specificity of the action of the drug.
All primary cultures were examined by electron microscopy before and following treatment with Permixon(R) (10 microg./ml.). In addition the apoptotic index was assessed by flow cytometry employing propidium iodide as a fluorophore. The impact of the drug on 5alpha-reductase (5alphaR) isoenzymes was also tested utilizing a pH specific assay.
There were changes in the morphology of prostate cells after treatment including accumulation of lipid in the cytoplasm and damage to the nuclear and mitochondrial membranes; no similar changes were observed in other cells. Permixon(R) increased the apoptotic index for prostate epithelial cells by 35% and 12% in the prostate stromal/fibroblast. A lesser apoptotic effect was demonstrated in skin fibroblast (3%) whereas none of the other primary cultures showed any increase in apoptosis when compared with the controls. Permixon(R) was also an effective inhibitor of both 5alphaR type I and II isoenzymes in prostate cells, but other cells showed no inhibition of 5alphaR activity following treatment with the plant extract.
This investigation demonstrated the selectivity of the action of Permixon(R) for prostate cells. The morphological changes in the prostate are accompanied by an increase in the apoptotic index along with an inhibition in the activity of the nuclear membrane bound 5alphaR isoenzymes. No similar changes were observed in any of the other cells under investigation.
Prostatic hyperplasia predominantly involves the stromal compartment of the gland and affects more than 70% of men of 70 years or older with or without obstructive symptoms of benign prostatic hyperplasia. A consensus view is emerging concerning the factors and control systems that modulate cell proliferation and connective tissue biology in the prostate. The purpose of this review is to discuss some of the recent work contributing to the latter in the context of the aetiology of benign prostatic hyperplasia.
Studies over the last 3-5 years have identified transforming growth factor beta, fibroblast growth factor and insulin-like growth factor family members as key regulators of cell proliferation and extracellular matrix turnover with interrelated activities. Recently, oestrogens, adrenergic signalling and inflammatory processes have been shown to impact and potentially perturb the balance between the activities of the above factors. These agents are all subject to alteration with age and as such are candidates for potential triggers of the initiation of stromal hyperplasia.
The current model for the control and dysregulation of prostatic stromal growth is discussed in relation to the pathogenesis of benign prostatic hyperplasia and future directions for research.
We determined the effect of baicalein on prostatic hyperplasia in experimental animal models. Prostatic hyperplasia was induced by testosterone propionate in mice and castrated rats and by transplantation of homologous strain fetal mice urogenital sinus in mice. With the histopathological examination, the efficacy of baicalein on prostate hyperplasia in experimental animals was evaluated by the activity of serum acid phosphatase (ACP) and the following norm of the prostate gland: the volume, wet weight, wet weight index, dry weight index, DNA contents and prostatic epithelial height and cavity diameter. Results showed that baicalein at doses of 260 and 130 mg/kg administrated intragastrically (i.g.) significantly inhibited prostatic hyperplasia in castrated rats induced by testosterone propionate compared with the negative control group (p<0.01). Baicalein at doses of 520 and 260 mg/kg (i.g.) also significantly inhibited prostatic hyperplasia in mice induced by transplantation of homologous strain fetal mouse urogenital sinus and by testosterone propionate (p<0.01). These results suggested that baicalein has an inhibitory effect on prostatic hyperplasia in experimental animals.
The inhibitory effects of methanol extracts of 19 edible and medicinal mushrooms on 5alpha-reductase activity were examined. The extract of Ganoderma lucidum Fr. Krast (Ganodermataceae) showed the strongest 5alpha-reductase inhibitory activity. The treatment of the fruit body of Ganoderma lucidum or the extract prepared from it significantly inhibited the testosterone-induced growth of the ventral prostate in castrated rats. These results showed that Ganoderma lucidum might be a useful ingredient for the treatment of benign prostatic hyperplasia (BPH).
Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that results in obstructive lower urinary tract symptoms. Saw palmetto (Serenoa repens), the dwarf American palm (Arecaceae family), is commonly used to treat BPH. The Cuban royal palm (Roystonea regia) also belongs to the Arecaceae family, and 200-400mg of D-004, a lipid extract from its fruits, administered orally for 14 days has been shown to prevent testosterone- but not dihydrotestosterone-induced prostatic hyperplasia in rats. D-004 (125-250 microg/mL) added to preparations of rat vas deferens caused a marked, dose-dependent and significant inhibition of noradrenaline-induced smooth muscle contraction, a response mediated through alpha(1)-adrenoceptors, and was more effective in these respects than Saw palmetto. However, the in vivo effects of D-004 and Saw palmetto on the hypertensive response induced by noradrenaline were modest (albeit significant), and neither treatment affected resting blood pressure or heart rate in rats. The differential effects of D-004 in in vitro and in vivo models could be related to a differential affinity for adrenoceptor subtypes or to different bioavailabilities in vascular and urogenital targets. Phenylephrine injected into rodents induces prostatic hyperplasia with all the characteristic morphological changes of the condition but does not result in enlargement of the prostate. Therefore, this phenylephrine-induced change in rat prostate tissue is called atypical prostatic hyperplasia. It serves as an in vivo model of prostatic hyperplasia induced by stimulation of alpha(1)-adrenoceptors. The objective of this study was to determine whether D-004 can inhibit induction of atypical prostatic hyperplasia by phenylephrine in rats.
Rats were randomly distributed into five groups (ten rats/group). One group was a negative control and received oral vehicle only. The other four groups were injected subcutaneously with phenylephrine (2 mg/kg): of these groups, one was a positive control receiving the vehicle, and the other three groups were treated with D-004 or Saw palmetto (both 400 mg/kg) or tamsulosin 0.4 mg/kg. All active treatments were given orally for 28 days. After completion of treatment, rats were placed unrestrained in metabolic cages and micturition studies were performed. The rats were later killed and their prostates removed and weighed. Prostate samples were processed for histological study, with histological changes being assessed according to a scoring system. Bodyweight was measured at baseline and at weekly intervals.
Histological examination of positive control rats revealed features of atypical prostatic hyperplasia, with piling-up, papillary and cribiform patterns and budding-out of epithelial cells. Micturition assessment revealed that phenylephrine significantly lowered both the total volume of urine in 1 hour and the volume per micturition; the latter was considered the main efficacy variable. D-004 and Saw palmetto extracts significantly prevented this reduction in volume per micturition by 70.5% and 68.6%, respectively, while tamsulosin totally abolished the reduction in micturition induced by phenylephrine (100% inhibition). Tamsulosin, D-004 and Saw palmetto significantly reduced the histological changes of atypical prostatic hyperplasia induced by phenylephrine by 73.1%, 61.2% and 50.0%, respectively.
Administration of D-004 resulted in marked and significant prevention of phenylephrine-induced impairment of micturition and histological changes in rat prostate. These findings indicate that, in vivo, D-004 effectively opposes these responses to phenylephrine, which are mediated through urogenital alpha(1)-adrenoceptors. In this respect, D-004 was moderately more effective than Saw palmetto, a phytotherapeutic standard used to treat BPH, but less effective than tamsulosin, a selective alpha(1A)-adrenoceptor antagonist.
Both androgens and estrogens play a significant role in the prostate and are critical for normal prostate growth and development, as well as the maintenance of adult prostatic homeostasis throughout life. It is the balance of these two hormones, rather than each individually, that is important for prostatic development and differentiation. Estrogen action is mediated by the estrogen receptors, ERalpha and ERbeta. ERalpha is expressed throughout the prostatic tissue during fetal and early neonatal life, and if activated inappropriately, produces late-life disease, including inflammation and emergence of pre-malignant pathologies. In contrast, ERbeta expression is initiated after ERalpha, is localized primarily to the epithelium, and appears to be important during later periods of development such as puberty and adulthood, acting to regulate cellular proliferation and differentiation in the adult tissue. Therefore, there is also a spatial and temporal balance between ERalpha and ERbeta that is critical for development. Together with the shifting balance between androgens and estrogens themselves, the subtle, yet critical, balance between the activity of ERalpha and ERbeta is what ultimately determines the response of the prostate to estrogen, and is crucial for prostate health.
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