Ventral Prostate Weight Research Articles

Efecto del extracto de Boswellia serrata sobre el daño testicular inducido por Metotrexato

This study aimed to determine the effect of Boswellia serrata extract on Methotrexate– induced testicular damage by evaluating antioxidant system, reproductive organ weights, some spermatological parametres and serum Testesterone levels. For this purpose, 40 Sprague Dawley rats were divided into 4 groups. 1. Control Group (n=10): No treatment was given for 10 days. 2. B. serrata Group (n=10): B. serrata was given by gavage at a dose of 500 mg·kg-1 for 10 days. 3. Methotrexate Group (n=10): Methotrexate was given intraperitoneally as a single dose of 20 mg·kg-1. 4. Methotrexate + B. serrata Group (n=10): After methotrexate was given intraperitoneally as a single dose of 20 mg·kg-1, 500 mg·kg-1 B. serrata was given by gavage for 10 days. It was determined that B. serrata significantly increased serum Testosterone levels (P<0.001), testicular GSH levels (P<0.001), motility of sperm (P<0.001), concentration of sperm (P<0.001), absolute ventral prostate (P<0.001) and absolute seminal vesicles (P<0.05) organ weight in Methotrexate + B. serrata group. The decrease in testicular MDA levels (P>0.05) and the increase in GSH–Px enzyme activity of testes (P>0.05) and final body weight (P>0.05) were not significant in Methotrexate + B. serrata group compared to the Methotrexate group. In conclusion, the negative effects of Methotrexate on the male reproductive system can be reduced by administering B. serrata extract.

(539) Preventive Effects of Pterorhachis Zenkeri Harm (Meliaceae) in Testosterone Propionate-induced Benign Prostatic Hypertrophy in Wistar Rat

Abstract Introduction Benign prostatic hypertrophy (BPH) is an androgen-dependent and age-related disease which significantly affects the patient’s life. BPH can lead to a number of symptoms for patients commonly referred to as lower urinary tract symptoms including obstructive and irritative disorders as well as complications such as renal failure and sexual disorders. In addition, medical health care remains problematic due to therapeutic limits such as the cost, the accessibility and the side effects. Objective The aim of the present study was to assess the preventive effects of the aqueous (62 mg/kg) and methanolic (10 mg/kg) extracts from Pterorhachis zenkeri (P. zenkeri) on testosterone propionate-induced benign prostatic hypertrophy in rats. Methods Adult Wistar rats were randomly partitioned into groups of 5 rats each and treated with one of the following: distilled water (10ml/kg)/soja oil (1 ml/kg), testosterone (10 mg/kg), aqueous extract (62 mg/kg), methanolic extract (10 mg/kg), testosterone plus bicalutamide (5 mg/kg) plus aqueous extract (62 mg/kg), testosterone plus bicalutamide plus methanol extract (10 mg/kg) during 2 or 4 weeks. At the end of the treatment periods, body and prostate related weight, biochemical, histological, histo-morphometrical and oxidative stress parameters were comparatively measured. Results Testosterone propionate induced a significant (p<0.001) increase in the size and relative weight of ventral prostate, plasmatic level of prostate specific antigen (PSA), length of prostate epithelial cells and prostate structural damages. Additionally, the levels of prostatic dihydrotestosterone and, plasmatic nitrogen monoxide and malondialdehyde were increased whereas the activity of superoxide dismutase was decreased. Administration or co-administrations of P. zenkeri extracts with bicalutamide time-dependently prevented the above-mentioned damages through its anti-androgenic and anti-oxidant properties. Conclusions The bioactive compounds present in P. zenkeri extracts could justify the reported findings. Present results therefore suggest that P. zenkeri could be a good candidate in the management of BPH. Disclosure No

Phytoecdysteroids and Anabolic Effect of Atriplex dimorphostegia: UPLC-PDA-MS/MS Profiling, In Silico and In Vivo Models.

Atriplex dimorphostegia (Saltbush) is an annual halophytic shrub that is widely distributed across various parts of Asia. The current study is the first to report the metabolites profile of the total ethanol extract of the aerial parts of A. dimorphostegia (TEAD), and its anabolic activity together with the isolated 20-hydroxyecdysone (20-HE) in orchidectomized male rats. TEAD was analyzed and standardized utilizing UPLC-PDA-ESI−MS/MS and UPLC-PDA-UV techniques, resulting in tentative identification of fifty compounds including polyphenols, steroids and triterpenoids. In addition, 20-HE was quantified, representing 26.79 μg/mg of the extract. Phytochemical investigation of TEAD resulted in the isolation of 20-HE from the ethyl acetate fraction (EFAD) and was identified by conventional spectroscopic methods of analysis. Furthermore, the anabolic effect of the isolated 20-HE and TEAD was then evaluated using in silico and in vivo models. Molecular docking experiments revealed in vitro selectivity of 20-HE towards estrogen receptors (ERs), specifically ERβ over ERα and androgenic receptor (AR). The anabolic efficacy of TEAD and 20-HE was studied in orchidectomized immature male Wistar rats using the weight of gastrocnemius and soleus muscles. The weights of ventral prostate and seminal vesicles were used as indicators for androgenic activity. Rats administered 20-HE and TEAD showed a significant increase (p = 0.0006 and p < 0.0001) in the net muscle mass compared to the negative control, while the group receiving TEAD showed the highest percentage among all groups at p < 0.0001. Histopathological investigation of skeletal muscle fibers showed normal morphological structures, and the group administered 20-HE showed an increase in cross sectional area of muscle fibers comparable to methandienone and testosterone groups at p > 0.99. A. dimorphostegia exhibited promising anabolic activity with minimal androgenic side effects.

Suppression of fertility by &lt;em&gt;Capparis spinosa&lt;/em&gt; root extract through antioxidant alteration in reproductive system of male rats

Aim: To evaluate the suppression of fertility by oral mode of Capparis spinosa root extract through alteration in antioxidant defence of the reproductive system of male albino rats. Methods: The methanol extract of Capparis spinosa root (100mg/kg/day) was fed for 60 days to male, Wistar strain, albino rats. The fertility and testicular functions were assessed by mating tests, antioxidant defence indices, and spermatogenesis, histometry, and biochemical estimations for fertility suppression along with serum biochemistry and hematology for assessment of toxicology. Results: Capparis spinosa root extract administration for a period of 60 days did not cause body weight loss significantly, while the weight of testes, Cauda epididymis, seminal vesicle, and ventral prostate were significantly reduced. The lipid peroxidation and antioxidants levels i.e. superoxide dismutase, catalase, glutathione reduced, glutathione peroxidase, vitamin C, and Vitamin E in testes, Cauda epididymis, seminal vesicle, and ventral prostate were altered significantly (P<0.001) after the 60 days treatment of Capparis spinosa extract when compared to the controls. The root extract feeding caused a marked reduction in the number of primary spermatocytes, secondary spermatocytes, and spermatids however spermatogonia population showed non-significant change. Sertoli cell population was also affected. The number of mature Leydig cells was decreased and degenerating cells increased proportionately. The seminiferous tubule and Leydig cell nuclear area were reduced significantly (P<0.001) when compared to the controls. The protein and sialic acid content of the testes, Cauda epididymis, seminal vesicle, and ventral prostate were significantly (P<0.001) decreased. The glycogen in testes and fructose in seminal vesicle was also significantly reduced, whereas the testicular cholesterol was elevated as compared with the controls. Reduced sperm count and motility resulted in a total suppression of fertility. The RBC and WBC count, hemoglobin, and hematocrit in whole blood whereas marker enzymes and glucose in serum were found to be within the normal range after the 60 days of Capparis spinosa extract treatment. Conclusion: Capparis spinosa root extract may selectively act on developing germ cells mediated via Sertoli cells through increased oxidative stress or impairment of antioxidant defence system in reproductive organs of male rats, leading to suppression of fertility and suggests the feasibility of developing non-toxic, herbal male contraceptive drug.

Inhibitory Effect of Astaxanthin on Testosterone-Induced Benign Prostatic Hyperplasia in Rats.

This study investigates the inhibitory effect of astaxanthin (AST) on testosterone-induced benign prostatic hyperplasia (BPH) in rats. Except for the sham operation, BPH model rats were randomly assigned to five groups: the BPH model control rats, AST-treated BPH model rats (20 mg/kg, 40 mg/kg, and 80 mg/kg), and epristeride (EPR)-treated BPH model rats. After treatment, as compared with the BPH model control rats, the prostate and ventral prostate weights of the AST-treated rats decreased, while there was a marked decline in the 80 mg/kg AST-treated rats. The same effect was also observed in the prostate index and ventral prostate index. The proliferation characteristics of epithelia observed in the BPH model control group were gradually alleviated in the AST-treated rats. As compared with the BPH model control rats, lower epithelial thicknesses of prostates and fewer secretory granules in epithelia were observed in the AST-treated rats. The superoxide dismutase (SOD) activity of prostates increased in all the AST-treated rats with a significant increase in the 40 mg/kg and 80 mg/kg AST-treated rats. The testosterone (T) and dihydrotestosterone (DHT) levels of prostates in the AST-treated groups were lower than those in the BPH model control group, and a significant decline was found in the T level of prostates in the 40 g/kg and 80 mg/kg AST-treated rats and the DHT level of prostates in the 40 mg/kg AST-treated rats. These results indicate that AST might have an inhibitory effect on T-induced BPH in rats, possibly due to SOD activity regulation and T and DHT levels.

Wistar albino sıçanlarda antioksidan özellikli bir bitkinin spermatogenez üzerine etkisi

Bu calismanin amaci sicanlarda Michauxia campanuloides L’Her. kullaniminin bazi sperma parametreleri uzerine etkisini arastirmaktir. Sunulan calismanin bitki materyali antioksidan ozellikli Michauxia campanuloides L’Her.'dir. Calismanin hayvan materyalini 18 adet erkek Wistar albino sican olusturmustur. Sicanlar kontrol (K; n=6), uygulama 1 (U1; n=6) ve uygulama 2 (U2; n=6) olmak uzere uc gruba ayrilmis ve M. campanuloides L’Her.'in liyofilize sulu ekstresi U1 grubundaki sicanlara 20 mg/kg ve U2 grubundaki sicanlara 40 mg/kg dozunda 21 gun sureyle oral yolla gunluk uygulandi. Calisma sonunda tum sicanlar kan serumu total antioksidan kapasitesi (TAK), sperma yogunlugu, sperma motilitesi, anormal spermatozoon orani ile testis, epididimis, seminal bez ve ventral prostat agirligi yonunden muayene edildi. Sperma yogunlugu K ve U1 gruplarina gore U2 grubunda anlamli duzeyde daha yuksek bulundu (P=0,002). Anormal spermatozoon oraninin K grubuna gore U1 ve U2 grubunda anlamli duzeyde daha dusuk oldugu tespit edildi (P=0,003). Seminal bez agirligi K grubuna gore U1 ve U2 gruplarinda istatistiksel olarak daha yuksek olculdu (P=0,016). Sonuc olarak, M. campanuloides ekstresinin oral tuketimi sicanlarda sperma kalitesinde bir artis saglamaktadir.

Phosphodiesterase type 5 inhibitor attenuates chronic ischemia-induced prostatic hyperplasia in a rat model.

Many elderly men suffer from benign prostatic hyperplasia (BPH). Recently, chronic ischemia in the prostate has been suggested to be related to BPH. Thus, the impact of chronic ischemia on the development of prostatic hyperplasia and the efficacy of phosphodiesterase type 5 (PDE5) inhibitor for hyperplasia were evaluated in a rat model with chronic ischemia induced by local atherosclerosis. Eighteen male Sprague-Dawley rats were divided into three groups: sham operation, regular diet, placebo (SRP); arterial endothelial injury, high cholesterol diet, placebo (AHP); or arterial endothelial injury, high cholesterol diet, and tadalafil as a PDE5 inhibitor (AHT). The endothelial injury in the common iliac arteries was performed using a 2-Fr Fogarty arterial embolectomy catheter through an incision in the femoral artery into the common iliac artery. Diet and oral drugs were administrated for 8 weeks after surgery. At 8 weeks, blood flow to the ventral prostate (VP) was measured using laser speckle blood flow analysis, and the VP was histologically evaluated. In the AHP group, prostatic blood flow was reduced, and mean VP weight and the interstitial area were significantly enlarged compared with the SRP group. In the AHT group, tadalafil administration obviously ameliorated the reduction of prostatic blood flow relative to the AHP group. Importantly, mean VP weight and the morphological changes in the AHT group were significantly smaller than those in the AHP group. Enlargement of the VP resulted from chronic ischemia induced by local arteriosclerosis. Also, administration of tadalafil attenuated VP enlargement. Chronic ischemia in the prostate might thus contribute to the development of BPH, and PDE5 inhibitors might provide an innovative approach to preventing BPH.

Estrogen imprinting compromises male sexual behavior and affects the number of androgen-receptor-expressing hypothalamic neurons†.

Neonatal exposure to high-dose 17β-estradiol (E2) affects the morphology and physiology of sex and accessory sex organs in the long term. In this study, we examined the effects of E2 imprinting on male sexual behavior, fertility, and the number of androgen receptor (AR)-expressing cells in the hypothalamus. E2-treated males showed copulatory behavior represented by mounts and/or intromissions, demonstrating the preservation of aspects of male behavior. They had slightly increased latency for first intromission and a reduced number of ejaculations, associated with a 50% reduction in the fertility index. AR expression in the hypothalamus was assessed by RT-PCR, western blotting, and immunohistochemistry. Treated rats had a significantly lower ventral prostate (VP) weight, demonstrating the efficacy of the treatment. The AR mRNA and protein content in the hypothalamus of E2-treated animals was reduced to the levels of females. AR-expressing cell counts in the ventromedial, anterior medial preoptic, paraventricular nuclei, and preoptic areas were different from control males, and similar to those of females. In conclusion, E2 imprinting resulted not only in ill-developed sexual organs, but also affected sexual behavior, resulting in a female-type hypothalamus, at least with respect to the abundance of AR mRNA and protein and the number of AR-expressing cells in important regions/tracts.

Modulation of inflammatory and hormonal parameters in response to testosterone therapy: Effects on the ventral prostate of adult rats.

Testosterone is often recommended in the treatment of several aging-related conditions. However, there are still questions about the consequences of this therapy in terms of hormonal and inflammatory parameters that are crucial for prostate homeostasis. Thus, we investigate if the testosterone therapy (TT) modulates the hormone receptors and inflammatory cytokines in the ventral prostate of adult rats. Wistar rats aging 150 days were divided into two experimental groups (n = 10/group): T: received subcutaneous injections of testosterone cypionate (5 mg/kg body weight) diluted in corn oil every other day for 4 weeks; and C: received corn oil as vehicle. Animals were euthanized at 180 days old by decapitation. Blood was collected to obtain hormone and cytokines concentrations. The ventral prostate was dissected and processed for light microscope and molecular analyses. Relative ventral prostate weight and epithelial compartment were increased after TT. The number of intact and degranulated mast cells was reduced in the T group. Plasma testosterone, DHT and intraprostatic testosterone concentrations were higher in the T group. TT leads to an increase in cell proliferation and up-regulation of AR, ERβ, PAR-4, and NRF2. Importantly, plasma concentration and tissue expression of IL-10 and TNF-α were higher after TT. In summary, these results indicate that TT can regulate inflammatory response, with impacts in cytokines and mast cell population, and modulates steroids receptors, important parameters for prostatic homeostasis.

Assessment of dose-dependent reproductive toxicity of diclofenac sodium in male rats

Diclofenac sodium is widely used in the non-steroidal anti-inflammatory drug in the treatment of pain and inflammation. It is also particularly associated with its adverse effects on avian fauna and linked to environmental issues. The present study was aimed to assess the dose-dependent toxicity of diclofenac sodium on a male reproductive system of rats. Four groups of healthy adult fertile male rats were administered with saline (control) or 0.25 mg/kg, 0.50 mg/kg and 1.0 mg/kg of diclofenac sodium, respectively for 30 days. Alterations in body and organ weight, sperm and testicular cell population dynamics, serum biochemistry, histopathology, and hematology were investigated as per aimed objectives. Diclofenac sodium treatment significantly (p ≤ 0.001) reduced weights of testis, epididymis, ventral prostate and seminal vesicle. Sperm count, sperm density (in epididymis and testis), sperm motility and testicular cell population dynamics were lowered in a dose-dependent manner. Administration of diclofenac exhibited varying degrees of degeneration testis, abnormal histo-architectures, and shrinkages in seminiferous tubules, particularly in higher doses. Diclofenac sodium treatments also altered hepatic and renal function parameters significantly. In conclusion, it may claim that diclofenac sodium treatment altered reproductive metabolic status, androgenic activities and histo-architecture of the testis of male rats and induced hepatotoxicity and renal toxicity.

Influence of postnatal prolactin modulation on the development and maturation of ventral prostate in young rats.

Besides androgenic dependence, other hormones also influence the prostate biology. Prolactin has been described as an important hormone associated with maintenance of prostatic morphophysiology; however, there is a lack of information on the involvement of prolactin during prostate development and growth. This study aimed to evaluate whether perinatal prolactin modulation interferes with rat ventral prostate (VP) development and maturation. Therefore, prolactin or bromocriptine (an inhibitor of prolactin release from the pituitary) were administered to Sprague Dawley rats from postnatal Day (PND) 12 to PND 21 or 35. Animals were then killed and serum hormonal quantification, VP morphological-stereological and immunohistochemical analyses and western blotting reactions were employed. Our results demonstrate that prolactin blockage increased serum testosterone on PND 21, which reflected an increase in anogenital distance. Although prolactin modulation did not interfere with VP weight, it modified VP morphology by dilating the acinar lumen and reducing epithelial cell height. Prolactin activated the signal transducer and activator of transcription (STAT) downstream pathway, increased androgen receptor expression and epithelial proliferation. In addition, prolactin and bromocriptine also increased expression of cytokeratin 18, a marker of luminal-differentiated cells. In conclusion, the VP responds to prolactin modulation through a mechanism of increasing the epithelial proliferative response and dynamics of cell differentiation, especially in animals treated for a more prolonged period.

Is immunosuppression, induced by neonatal thymectomy, compatible with poor reproductive performance in adult male rats?

With increasing knowledge that the immune system has a major impact on reproductive ‎health, the potential for cells arising in organs such as the thymus to alleviate oxidative stress ‎has been revealed. This study addresses the impact of neonatal thymectomy on male ‎reproductive function in pubertal and adult animals. Neonatal Sprague Dawley rats were allotted to four treatments consisting of fully thymectomized, partially thymectomized, intact, and sham-operated rats. Half of the rats in each treatment were sacrificed at 40 and the other half at 80days of age. Testicular volume, ventral prostate and spleen weight, several sperm attributes (concentration, motility, livability, membrane integrity, sperm penetration into mucus, total antioxidant capacity, mitochondrial dehydrogenase activity), plasma superoxide dismutase, glutathione, and testosterone level as well as fertility decreased in thymectomized rats. Adrenal gland weight, sperm malondialdehyde level, indices of oxidative stress, sperm abnormality, testicular and sperm lipid peroxidation, protein carbonylation, and sperm reactive oxygen species generation increased in thymectomized rats. In thymectomized rats, the testes contained high levels of malondialdehyde but low levels of glutathione and ferric-reducing antioxidant power. Epididymal sperm reactive oxygen species, blood lipid peroxidation, and oxidative stress indices ‎‎in blood and spermatozoa were highest in fully thymectomized, intermediate ‎in partially thymectomized, and lowest in both pubertal and mature control rats. Blood levels of superoxide dismutase, lipid peroxidation indices, and ‎testosterone, and mitochondrial adenosine triphosphate and ‎dehydrogenase activities in epididymal spermatozoa were lowest in fully thymectomized, ‎intermediate in partially thymectomized, and highest in both pubertal and mature control rats.‎ The data indicated that increased oxidative stress and mitochondrial dysfunction might play a role in the mechanism of immunosuppression-induced testicular and sperm abnormalities.

Investigations on the dose\u2013response relationship of combined exposure to low doses of three anti-androgens in Wistar rats

The current investigation examines whether combined exposure to three anti-androgens (flutamide, prochloraz, vinclozolin) result in interference with endocrine homeostasis when applied at very low dose levels, and whether the results of combined exposure are more pronounced than to the individual compounds. A pre–post-natal in vivo study design was chosen with more parameters than regulatory testing protocols require (additional endpoints addressing hormone levels, morphology and histopathological examinations). Dose levels were chosen to represent the lowest observed adverse effect level (LOAEL), the no observed adverse effect level (NOAEL), and the acceptable daily intake for each individual substance. Anti-androgenic changes were observable at the effect level (LOAEL) but not at lower exposures. Nipple/areola counts appeared to be a sensitive measure of effect, in addition to male sex organ weights at sexual maturation, and finally gross findings. The results indicate the absence of evidence for effects at low or very low dose levels. No (adverse) effects were seen at the NOAEL dose. A non-monotonic dose–response relationship was not evident. Combined exposure at LOAEL level resulted in enhanced responses for anogenital index, number of areolas/nipples, delayed preputial separation and reduced ventral prostate weight in comparison to the individual compounds.

Chemical characterization of vinclozoline M5 metabolite

The rodent Hershberger assay proposed by the Organization for Economic Co-operation and Development (OECD) is in the process of the validating a test method to detecting the androgenic or anti-androgenic compounds. The aim of this study was to compare the anti-androgenic properties of flutamide, vinclozolin, procymidone, linuron, and p,p′-DDE in a 10-day Hershberger assay. In the present study, we used immature Sprague–Dawley male rats castrated at 6 weeks of age. Testosterone propionate (TP) was subcutaneously injected for 10 consecutive days at doses of 0.1, 0.2, 0.4, 0.8, or 1.6 mg/kg per day. To compare the anti-androgenic activity of test compounds, flutamide (1, 5, 10, or 20 mg/kg per day), a pure androgen antagonist was used as a positive control, and administered by oral gavage after TP (0.4 mg/kg per day) treatment. In addition, vinclozolin (25, 50, or 100 mg/kg per day), procymidone (25, 50, or 100 mg/kg per day), linuron (25, 50, or 100 mg/kg per day), and p,p ′-DDE (25, 50, or 100 mg/kg per day) were also administered by oral gavage after TP (0.4 mg/kg per day) treatment. As expected, TP dose-dependently increased accessory sex organ weights, and statistically significant effects were observed at doses of 0.1 (only seminal vesicles) or 0.2 mg/kg per day and above. Serum testosterone levels increased significantly at 0.4 mg/kg per day and above, while serum LH levels were decreased in a dose-dependent manner. Flutamide significantly inhibited the TP-induced re-growth of seminal vesicles, ventral prostate, and Levator ani plus bulbocavernosus muscles (LABC) at 1 mg/kg per day and above, and Cowper’s glands and glans penis at 5 mg/kg per day and above. In contrast to accessory sex organ weights, flutamide did not affect the serum testosterone levels compared to the control at any concentration, but serum LH levels were significantly increased at doses of 10 and 20 mg/kg per day. Similar to flutamide, vinclozolin caused a statistically significant decrease in the weights of seminal vesicles (to 65 and 40% of the control), ventral prostate (to 66 and 51% of the control), LABC (to 81 and 66% of the control), and Cowper’s glands (to 81 and 65% of the control) at 50 and 100 mg/kg per day, respectively. Glans penis weight was also significantly reduced (to 79% of the control), but only at 100 mg/kg per day. The most pronounced effects were observed in the procymidone treatment groups. Procymidone significantly inhibited TP-induced re-growth of accessory sex organs at 25 mg/kg per day and above, whereas glans penis weight significantly decreased (to 69% of the control), but only at 100 mg/kg per day. Linuron also inhibited TP-induced re-growth of the seminal vesicles (to 72 and 53% of the control), ventral prostate (to 75 and 62% of the control), Cowper’s glands (to 74 and 61% of the control) at 50 and 100 mg/kg per day, respectively. LABC (to 65% of the control) and glans penis (to 80% of the control) weights were significantly reduced, but only at 100 mg/kg per day. In case of p,p ′-DDE, seminal vesicle weights were significantly decreased at 50 (to 66% of the control) and 100 mg/kg per day (to 58% of the control). In addition, ventral prostate (to 79% of the control), LABC (to 75% of the control), and Cowper’s gland (to 82% of the control) weights were reduced, but only at 100 mg/kg per day. On the contrary, no statistically significant differences in serum testosterone or LH levels were observed versus the control. p,p′-DDE significantly increased liver weight in a dose-dependent manner, without affecting on body weights. Our results indicate that procymidone may act as a stronger androgen receptor (AR) antagonist than vinclozolin, linuron, or p,p′-DDE. We conclude that the 10-day Hershberger assay is a sensitive method for detecting potential anti-androgenic compounds.

Safety evaluation (acute and sub-acute studies) of the aqueous extract of the leaves of Myrianthus arboreus P. Beauv. (Cecropiaceae) in Wistar rats

Ethnopharmacological relevanceMyrianthus arboreus P. Beauv (Cecropiaceae) is a medicinal plant distributed in forests and damp places of tropical Africa. Its leaves are widely used as food and/or for the treatment of various ailments including dysmenorrhoea, female infertility, tumors and diarrhea. However, to the best of our knowledge, no safety assessment of this plant has been reported yet. Aim of studyThe present study aimed at evaluating the safety of the aqueous extract of leaves of Myrianthus arboreus (MAA) in Wistar rats through an acute and sub-acute oral administration. Material and methodsIn acute oral toxicity, the test was performed according to the Organization for Economic Cooperation and Development (OECD) guidelines Nr. 423 (acute toxicity class method, ATC) with slight modifications. Female Wistar rats were orally treated with the aqueous extract of M. arboreus at the doses of 2000 and 5000mg/kg. In sub-acute toxicity study, using the OECD guidelines Nr. 407, the extract was administered by gavage at the doses of 20, 110 and 200mg/kg/day for 28 consecutive days. ResultsA single oral administration of 2000 or 5000mg/kg of the extract induced neither mortality nor exterior signs of toxicity indicating a LD50 >5000mg/kg. In sub-acute study, the extract decreased triglycerides, total cholesterol/high density lipoproteins ratio and atherogenic index of plasma in both sexes at all tested doses. Alanine transaminase decreased in both sexes at 200mg/kg and serum creatinine levels decreased at all tested doses in females. Moreover, significant increases in ovarian and uterine wet weights, red blood cell count, hematocrit, mean corpuscular hemoglobin and hemoglobin were observed at 200mg/kg in females. In males, this extract decreased white blood cell count, lymphocytes and relative weight of seminal vesicles and ventral prostate at 200mg/kg. ConclusionThe aqueous extract of Myrianthus arboreus leaves was non-toxic in acute administration and exhibited a relatively low toxicity potential on accessory sex organs in both sexes, and leukocytes in males following the repeated 28-days oral administration of the dose 200mg/kg.

Long-term adverse effects on reproductive function in male rats exposed prenatally to the glucocorticoid betamethasone.

Betamethasone is the drug of choice for antenatal treatment, promoting fetal lung maturation, decreasing the incidence of respiratory distress syndrome and neonatal mortality. Previous studies reported that prenatal treatment with this drug reduced testosterone levels, sperm quality and fertility in adult rats. We aimed to further evaluate the reproductive consequences of prenatal betamethasone exposure in male rats. Pregnant Wistar rats (n=13/group) were separated into two groups: control (vehicle) and betamethasone- treated (0.1mg/kg IM) and rats were injected on gestational days 12, 13, 18 and 19. Body weight, sexual behavior, reproductive organ weights, serum hormone levels, accessory glands contractility, sperm parameters, and fertility after in utero artificial insemination were evaluated. Our results showed that prenatal betamethasone exposure provoked a significant reduction in body weight at PND 01 and, at adulthood, decrease in FSH levels, sperm motility and production. Furthermore, seminal vesicle weight was decreased while testicular and ventral prostate weights were increased. Serum LH levels and the percentage of abnormal sperm were significantly increased. Although sexual behavior was not altered, a significant reduction in fertility in the adult rats exposed prenatally to betamethasone was noted. We concluded that prenatal betamethasone exposure leads to long-term reproductive impairment in male rats. These results may have important implications for humans, considering the use of this glucocorticoid in pregnant women.

Effect of gamma irradiation on phenol content, antioxidant activity and biological activity of black maca and red maca extracts (Lepidium meyenii walp)

This study was performed to determine the effects of gamma irradiation on UV spectrum on maca, total content of polyphenols, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activities and in vivo biological activities of red and black maca extracts (Lepidium meyenii).Adult mice of the strain Swiss aged 3 months and weighing 30–35 g in average were used to determine biological activities. Daily sperm production, effect on testosterone-induced prostate hyperplasia and forced swimming test were used to determine the effect of irradiation on biological activities of maca extracts.Irradiation did not show differences in UV spectrum but improves the amount of total polyphenols in red maca as well as in black maca extracts. In both cases, black maca extract has more content of polyphenols than red maca extract (p < 0.01). Gamma irradiation significantly increased the antioxidant capacity (p < 0.05).No difference was observed in daily sperm production when irradiated and nonirradiated maca extract were administered to mice (p > 0.05). Black maca extract but not red maca extract has more swimming endurance capacity in the forced swimming test. Irradiation of black maca extract increased the swimming time to exhaustion (p < 0.05). This is not observed with red maca extract (p > 0.05). Testosterone enanthate (TE) increased significantly the ventral prostate weight. Administration of red maca extract in animals treated with TE prevented the increase in prostate weight. Irradiation did not modify effect of red maca extract on prostate weight (p > 0.05).In conclusion, irradiation does not alter the biological activities of both black maca and red maca extracts. It prevents the presence of microorganisms in the extracts of black or red maca, but the biological activities were maintained.

Abstract 827: Analysis of p63 protein expression in rat ventral prostate submitted to intrauterine undernutrition associated to hormonal exposure in adult life

Abstract Basal cells expressing p63 contain multipotent stem cells that can efficiently differentiate during postnatal prostate morphogenesis, adult prostate epithelial homeostasis and carcinogenesis. Our project aim is to investigate p63 expression by focusing on the rates of basal epithelial cell proliferation/differentiation in the ventral prostate after intrauterine undernutrition (IUN) associated with or without hormonal exposure in adult life. Briefly, 20 Sprague Dawley dams were distributed equally into two groups during gestation: control diet (NP; fed a normal diet containing 17% protein) and restricted protein diet (RP, fed a diet containing 6% protein). After birth, all animals were maintained on the control diet. Experiment 1: To analyze p63 expression during prostate development, NP and RP animals were euthanized at postnatal day (PND) 3, 10, 21 and 35. The ventral prostate (VP) was dissected, weighed and processed for IHC (Ki67, p63 and AR) and Western blot (WB) analysis (PCNA, p63 and AR). Experiment 2: To analyze p63 expression in adults after hormonal exposure, 14 week-old NP and RP animals were subjected to 17-beta estradiol+testosterone administration (subcutaneous implant) for 16 weeks. The animals were killed at 35 weeks old and the VP was excised, weighed and processed for IHC and WB analysis. RP treated animals showed lower body weight compared to NP control treated animals. Reductions of testosterone plasma levels as well as the absolute and relative values of VP weights from the RP animals compared to the NP animals were observed. Normal glandular architecture was observed in both groups at PND 3, 10, 21 and 35. There was a reduction of AR expression in VP from RP animals at all ages analyzed. However, the proliferation rate and p63+ cells were higher in the RP group indicating that the low androgenic stimulation induced by IUN promoted a delay in VP development. As a consequence, the proliferation/differentiation cell dynamic was impaired, leading to an increase in basal cell number and damaging their differentiation into secretory luminal cells. We observed in hormone exposed adults that prostatitis aggressiveness and prostatic intraepithelial neoplasia (PIN) incidence were higher in the RP compared to NP animals. These results were followed by a decrease in apoptosis index and increases in proliferation rate and p63+ cells. It is clear that IUN alters adult prostate response to androgen/estrogen exposure and interferes in adult prostate susceptibility to diseases. In conclusion, IUN-induced fetal programming impairs ventral prostate growth, maturation and homeostasis highlighting the importance of adequate nutritional status during embryonic/fetal development. Note: This abstract was not presented at the meeting. Citation Format: Jaqueline C. Rinaldi, Caroline N. Barquilha, Sergio AA Santos, Ana C. Camargo, Ketlin T. Colombelli, Sergio L. Felisbin, Luis A. Justulin. Analysis of p63 protein expression in rat ventral prostate submitted to intrauterine undernutrition associated to hormonal exposure in adult life. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 827. doi:10.1158/1538-7445.AM2015-827

Effect of etodolac hydrazone, a new compound synthesised from etodolac, on spermatozoon quality, testicular lipid peroxidation, apoptosis and spermatozoon DNA integrity

The aim of this study was to investigate the effect of etodolac hydrazone (EH), a new compound synthesised from etodolac, on spermatozoon quality, testicular lipid peroxidation, apoptosis and spermatozoon DNA integrity in rats. Group 1 (n=8) received 1ml dimethyl sulfoxide (DMSO) daily (Control); group 2 (n=8) was treated with 5mgkg(-1) day(-1) EH, dissolved in 1ml DMSO (EH-5); and group 3 (n=8) was treated with 10 mg kg(-1) day(-1) EH, dissolved in 1ml DMSO (EH-10). All administrations were performed by gavage and maintained for 8weeks. Both doses of EH administration caused significant decreases in absolute and relative weights of testis, whole epididymis, right cauda epididymis, and spermatozoon motility, spermatozoon count in comparison with the control group. Only 10mgkg(-1) day(-1) EH administration caused significant decreases in absolute and relative weights of seminal vesicles and serum testosterone level, and significant increases in testicular lipid peroxidation level, and numbers of TUNEL+ apoptotic germ cells and spermatozoa with damaged DNA along with some histopathological damages when compared to the control group. However, body and ventral prostate weight, and testicular antioxidant markers (glutathione, glutathione-peroxidase and catalase), were unaffected significantly by both doses of EH administration. In conclusion, two different doses of EH, in particular its high dose, damage to testicular spermatogenic cells and spermatozoon DNA and, it decreases spermatozoon motility, count and testosterone level in healthy rats.

Effects of the 5α-reductase Inhibitor Dutasteride on Rat Prostate α1A-adrenergic Receptor and Its Mediated Contractility

To clarify the possible interference of the 5α-reductase inhibitor dutasteride with α-adrenergic blockers, whose action is mainly mediated by α1A-adrenergic receptor. Male rats were divided into dutasteride and vehicle-treated groups. The drug treatment group was treated with oral dutasteride 0.5 mg/kg/d, and the control group received vehicle only for 2 months. After the 2-month treatment, the rats' ventral prostate weight changes and the testosterone and dihydrotestosterone levels in the serum were measured. In vitro organ-bath studies, real-time polymerase chain reaction, and tissue-segment binding were performed to determine the expression of α1A-adrenergic receptors and its mediated contractility. Dutasteride treatment significantly decreased the rats' ventral prostate weight, increased their testosterone levels, and decreased the dihydrotestosterone levels in their serum. There were no marked changes in the α1A-adrenergic receptor messenger ribonucleic acid expression, relative phenylephrine-induced contractility, or nerve-mediated contractility between the groups. Dutasteride treatment caused no marked changes in the relative binding capacity of α1A-adrenergic receptor, whereas it greatly decreased the total protein expression of this subtype and its mediated maximal contraction in the whole ventral prostate. These results suggest that dutasteride does not interfere with α-adrenergic blockers but otherwise has beneficial effects on their actions. Therefore, the long-term administration of the combination of dutasteride with an α-adrenergic blocker might be a better choice for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia.