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1.
Urologiia ; (4): 175-179, 2019 Sep.
Artigo em Russo | MEDLINE | ID: mdl-31535827

RESUMO

The results of studies comparing the therapy of benign prostatic hyperplasia with 5-reductase inhibitors and 1-blockers are presented in the article. Benign prostatic hyperplasia is a common disease in older men. Pathogenetic treatment allows to block a progression of prostatic hyperplasia and is of greatest interest in the treatment of this disease. The obtained data reliably demonstrate the advantage and safety of long-term pathogenetic therapy with dutasteride compared with symptomatic tamsulosin monotherapy with regard to quality of life and subjective symptoms. In addition, pathogenetic therapy provides better results in preventing the progression of benign prostatic hyperplasia.


Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Idoso , Azasteroides , Quimioterapia Combinada , Dutasterida , Humanos , Masculino , Oxirredutases , Qualidade de Vida , Sulfonamidas , Resultado do Tratamento
3.
ACS Comb Sci ; 21(1): 11-27, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30576125

RESUMO

Herein, we report the synthesis of a novel class of substituted androst[17,16- b]pyridines (pyridosteroids) from the reaction of ß-formyl enamides with alkynes in high yields. The optimized reaction protocol was extended to acyclic and cyclic ß-formyl enamides to afford nonsteroidal pyridines. Cell survival assay of all compounds were carried against prostate cancer PC-3 cells wherein 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine showed the highest cytotoxic activity. Phase contrast microscopy and flow cytometry studies exhibited marked morphological features characteristic of apoptosis in 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine and abiraterone treated PC-3 cells. The treatment of 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine induces G2/M phase cell cycle arrest in prostate cancer PC-3 cells. Enhancement of apoptotic inductions of PC-3 cells by 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine and abiraterone through the activation of caspases-6, -7, and -8 pathways were supported by qRT-PCR. In silico study of the compound 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine showed stable and promising interaction with the key caspase proteins. Our studies revealed that the pyridosteroid 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine, bearing pyridine-2,3-dicarbethoxy pharmacophore, facilitated initiation of caspase-8 and activates downstream effectors caspase-6 and caspase-7 and thereby triggering apoptosis of PC-3 cancer cells.


Assuntos
Antineoplásicos/síntese química , Inibidores de Caspase/síntese química , Piridinas/síntese química , Esteroides/síntese química , Alquinos/química , Androstenos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Azasteroides/química , Inibidores de Caspase/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Piridinas/farmacologia , Esteroides/farmacologia , Relação Estrutura-Atividade , Termodinâmica
5.
Nat Commun ; 9(1): 934, 2018 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-29507290

RESUMO

Ring expansion provides a powerful way of introducing a heteroatom substituent into a carbocyclic framework. However, such reactions are often limited by the tendency of a given substrate to afford only one of the two rearrangement products or fail to achieve high selectivity at all. These limitations are particularly acute when seeking to carry out late-stage functionalization of natural products as starting points in drug discovery. In this work, we present a stereoelectronically controlled ring expansion sequence towards selective and flexible access to complementary ring systems derived from common steroidal substrates. Chemical diversification of the reaction intermediate affords over 100 isomerically pure analogs with spatial and functional diversity. This regiodivergent rearrangement, and the concept of using chiral reagents to affect regiocontrol in chiral natural products, should be broadly applicable to late-stage natural product diversification programs.


Assuntos
Azasteroides/síntese química , Estrutura Molecular , Estereoisomerismo
6.
J Biomed Mater Res B Appl Biomater ; 106(3): 1329-1338, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28688149

RESUMO

Clinical data show that in vitro contact lens friction is related to in vivo comfort. Solutions of biological lubricants hyaluronan (HA) and proteoglycan 4 (PRG4, also known as lubricin) reduce friction at a cornea-polydimethylsiloxane (PDMS) interface. The purpose of this study was to (1) determine if PRG4 can sorb to and lubricate model contact lens materials and (2) assess the boundary lubricating ability of PRG4 and HA compared to saline on model contact lens materials. PRG4 was obtained from bovine cartilage culture and suspended in saline at 300 µg/mL. N,N-Dimethylacrylamidetris (trimethylsiloxy) silane, (DMAA/TRIS) and methacryloxypropyltris (trimethylsiloxy) silane (pHEMA/TRIS) silicone hydrogels were prepared. A previously described in vitro eyelid-hydrogel and cornea-hydrogel biomechanical friction test was used to determine boundary lubricant effect. PRG4 sorption to the hydrogels was assessed using a soak-rinse protocol and western blotting. PRG4 effectively lubricated both silicone hydrogel materials and HA effectively lubricated pHEMA/TRIS, as indicated by a statistically significant reduction in friction compared to the saline control lubricant. An HA and PRG4 combination showed a synergistic effect for pHEMA/TRIS and effectively lubricated DMAA/TRIS. Biological boundary lubricants HA and PRG4 were shown to effectively lubricate silicone hydrogels when in solution. Additionally, HA and PRG4 showed synergistic lubrication for pHEMA/TRIS. The purpose of this study was not to replicate the friction coefficients of contact lenses, but rather to investigate lubricant-surface interactions for common contact lens constituents. These findings contribute to the potential development of biomolecule based lubricant drops for contact lens wearers. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1329-1338, 2018.


Assuntos
Soluções para Lentes de Contato , Ácido Hialurônico/farmacologia , Hidrogéis , Lubrificantes/farmacologia , Proteoglicanas/farmacologia , Idoso , Idoso de 80 Anos ou mais , Animais , Azasteroides/química , Fenômenos Biomecânicos , Bovinos , Córnea/efeitos dos fármacos , Di-Hidrotestosterona/análogos & derivados , Di-Hidrotestosterona/química , Pálpebras/efeitos dos fármacos , Fricção , Humanos , Pessoa de Meia-Idade , Poli-Hidroxietil Metacrilato , Silicones
8.
Bioorg Med Chem ; 25(16): 4452-4463, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28693914

RESUMO

Breast cancer cell proliferation is promoted by a variety of mitogenic signals. Classically estrogen is considered as most predominant mitogenic signal in hormone-dependent breast cancer and progesterone is primarily considered to have protective effect. However, it is suggested that some progesterone metabolite may promote breast cancer and progesterone metabolites like 5α-pregnane and 4-pregnene could serve as regulators of estrogen-responsiveness of breast cancer cells. Here, we estimated the potential of alternate targeting of breast cancer via progesterone signalling. l-Proline derived novel 14-azasteroid compounds were screened against MCF-7 and MDA-MB-231 cell lines using MTT assay. In silico studies, cell cycle, Annexin-V-FITC/PI, JC-1 mitochondrial assay, ROS analysis were performed to analyse the impact of hit compound 3b on breast cancer cells. Further, we analysed the impact of hit 3b on the progesterone, its metabolites and enzymes responsible for the conversion of progesterone and its metabolites using ELISA. Data suggests that compound 3b binds and down regulates of 5α-reductase by specifically inhibiting production of progesterone metabolites that are capable of promoting breast cancer proliferation, epithelial mesenchymal transition and migration. This study establishes the proof of concept and generation of new leads for additional targeting of breast cancer.


Assuntos
Antineoplásicos/farmacologia , Azasteroides/farmacologia , Neoplasias da Mama/tratamento farmacológico , Progesterona/antagonistas & inibidores , Prolina/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Azasteroides/síntese química , Azasteroides/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Modelos Moleculares , Estrutura Molecular , Progesterona/metabolismo , Prolina/química , Relação Estrutura-Atividade
9.
PLoS One ; 11(12): e0169116, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28036382

RESUMO

The food- and airborne fungal genus Wallemia comprises seven xerophilic and halophilic species: W. sebi, W. mellicola, W. canadensis, W. tropicalis, W. muriae, W. hederae and W. ichthyophaga. All listed species are adapted to low water activity and can contaminate food preserved with high amounts of salt or sugar. In relation to food safety, the effect of high salt and sugar concentrations on the production of secondary metabolites by this toxigenic fungus was investigated. The secondary metabolite profiles of 30 strains of the listed species were examined using general growth media, known to support the production of secondary metabolites, supplemented with different concentrations of NaCl, glucose and MgCl2. In more than two hundred extracts approximately one hundred different compounds were detected using high-performance liquid chromatography-diode array detection (HPLC-DAD). Although the genome data analysis of W. mellicola (previously W. sebi sensu lato) and W. ichthyophaga revealed a low number of secondary metabolites clusters, a substantial number of secondary metabolites were detected at different conditions. Machine learning analysis of the obtained dataset showed that NaCl has higher influence on the production of secondary metabolites than other tested solutes. Mass spectrometric analysis of selected extracts revealed that NaCl in the medium affects the production of some compounds with substantial biological activities (wallimidione, walleminol, walleminone, UCA 1064-A and UCA 1064-B). In particular an increase in NaCl concentration from 5% to 15% in the growth media increased the production of the toxic metabolites wallimidione, walleminol and walleminone.


Assuntos
Basidiomycota/genética , Basidiomycota/metabolismo , Ambientes Extremos , Micotoxinas/metabolismo , Metabolismo Secundário/genética , Cloreto de Sódio/metabolismo , Azasteroides/metabolismo , Basidiomycota/classificação , Colestadienóis/metabolismo , Cromatografia Líquida de Alta Pressão , Contaminação de Alimentos , Microbiologia de Alimentos , Glucose/metabolismo , Cloreto de Magnésio/metabolismo , Metabolismo Secundário/fisiologia , Sesquiterpenos/metabolismo
10.
J Steroid Biochem Mol Biol ; 163: 88-97, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27106747

RESUMO

The androgen receptor (AR) is a member of the nuclear hormone receptor super family of transcription factors. Androgens play an essential role in the development, growth, and maintenance of male sex organs, as well as the musculoskeletal and central nervous systems. Yet with advancing age, androgens can drive the onset of prostate cancer, the second leading cause of cancer death in males within the United States. Androgen deprivation therapy (ADT) by pharmacologic and/or surgical castration induces apoptosis of prostate cells and subsequent shrinkage of the prostate and prostate tumors. However, ADT is associated with significant musculoskeletal and behavioral adverse effects. The unique pharmacological activity of selective androgen receptor modulator (SARM) MK-4541 recently has been reported as an AR antagonist with 5α-reductase inhibitor function. The molecule inhibits proliferation and induces apoptosis in AR positive, androgen dependent prostate cancer cells. Importantly, MK-4541 inhibited androgen-dependent prostate growth in male rats yet maintained lean body mass and bone formation following ovariectomy in female rats. In the present study, we evaluated the effects of SARM MK-4541 in the androgen-dependent Dunning R3327-G prostate carcinoma xenograft mouse model as well as on skeletal muscle mass and function, and AR-regulated behavior in mice. MK-4541 significantly inhibited the growth of R3327-G prostate tumors, exhibited anti-androgen effects on the seminal vesicles, reduced plasma testosterone concentrations in intact males, and inhibited Ki67 expression. MK-4541 treated xenografts appeared similar to xenografts in castrated mice. Importantly, we demonstrate that MK-4541 exhibited anabolic activity in androgen deficient conditions, increasing lean body mass and muscle function in adult castrated mice. Moreover, MK-4541 treatment restored general activity levels in castrated mice. Thus, MK-4541 exhibits an optimum profile as an adjuvant therapy to ADT which may provide potent anti-androgenic activity at the prostate yet protective activity on skeletal muscle and behavior in patients.


Assuntos
Anabolizantes/farmacologia , Antagonistas de Androgênios/farmacologia , Antineoplásicos/farmacologia , Azasteroides/farmacologia , Carbamatos/farmacologia , Carcinoma/tratamento farmacológico , Músculo Esquelético/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Animais , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patologia , Quimioterapia Adjuvante/métodos , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Músculo Esquelético/metabolismo , Orquiectomia , Próstata/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Testosterona/antagonistas & inibidores , Testosterona/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Prostate ; 75(13): 1492-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26184556

RESUMO

BACKGROUND: To evaluate whether baseline acute and chronic prostate inflammation among men with initial negative biopsy for prostate cancer (PC) is associated with PC volume at the 2-year repeat prostate biopsy in a clinical trial with systematic biopsies. METHODS: Retrospective analysis of 886 men with negative baseline prostate biopsy and positive 2-year repeat biopsy in the Reduction by Dutasteride of PC Events (REDUCE) study. Acute and chronic inflammation and tumor volume were determined by central pathology. The association of baseline inflammation with 2-year repeat biopsy cancer volume was evaluated with linear and Poisson regressions controlling for demographics and laboratory variables. RESULTS: Chronic, acute inflammation, and both were detected in 531 (60%), 12 (1%), and 84 (9%) baseline biopsies, respectively. Acute and chronic inflammation were significantly associated with each other (P < 0.001). Chronic inflammation was associated with larger prostate (P < 0.001) and lower pre-repeat biopsy PSA (P = 0.01). At 2-year biopsy, baseline chronic inflammation was associated with lower mean tumor volume (2.07 µl vs. 3.15 µl; P = 0.001), number of biopsy cores involved (1.78 vs. 2.19; P < 0.001), percent of cores involved (17.8% vs. 22.8%; P < 0.001), core involvement (0.21 µl vs. 0.31 µl; P < 0.001), and overall percent tumor involvement (1.40% vs. 2.01%; P < 0.001). Results were unchanged in multivariable analysis. Baseline acute inflammation was not associated with any tumor volume measurement. CONCLUSION: In a cohort of men with 2-year repeat prostate biopsy positive for PC after a negative baseline biopsy, baseline chronic inflammation was associated with lower PC volume.


Assuntos
Inflamação/patologia , Próstata/patologia , Neoplasias da Próstata/patologia , Prostatite/patologia , Inibidores de 5-alfa Redutase/uso terapêutico , Idoso , Azasteroides/uso terapêutico , Biópsia , Dutasterida , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/tratamento farmacológico , Carga Tumoral
15.
Eur J Cancer ; 51(12): 1555-69, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26048455

RESUMO

BACKGROUND: Bicalutamide blocks androgen action and is frequently used in men with non-metastatic, castration-resistant prostate cancer (CRPC). By reducing intracellular dihydrotestosterone, dutasteride (dual 5-alpha reductase inhibitor) could increase the effectiveness of bicalutamide in this setting. The objective of the study is therefore to prospectively evaluate dutasteride plus bicalutamide in men with asymptomatic, non-metastatic CRPC with rising prostate-specific antigen (PSA). METHODS: Prostate cancer patients with rising PSA whilst on first-line androgen deprivation therapy (ADT) were randomised (1:1) in a double-blind trial to receive bicalutamide 50mg plus placebo or bicalutamide 50mg plus dutasteride 3.5mg once daily for 18 months. Randomisation was stratified by centre; treatment assignments were generated using GlaxoSmithKline's RandAll System. Subjects who completed 18 months could participate in the 2-year extension. Central laboratory and study sites/monitors remained treatment-blinded. Primary end-point was time to disease progression (TDP) up to 42 months (defined as PSA progression from baseline or nadir, radiographic disease progression, death from prostate cancer or receipt of rescue medication). FINDINGS: There was no statistically significant difference in TDP in 127 men treated with bicalutamide/dutasteride (n=62) compared with bicalutamide/placebo (n=65) (hazard ratio (HR)=0.94 [95% confidence interval (CI) 0.61, 1.46]; p=0.79). The estimated median TDP was 425 days (95% CI 302, 858) in the bicalutamide/placebo group and 623 days (95% CI 369, 730) in the bicalutamide/dutasteride group. There was no statistically significant difference between the treatment groups for any secondary efficacy end-points, including time to treatment failure or PSA response. In the multivariate analysis, age, non-White race, higher baseline testosterone and lower baseline PSA were associated with longer TDP. Adverse events were comparable between treatment groups. INTERPRETATION: In men with non-metastatic CRPC, adding dutasteride to bicalutamide did not significantly prolong TDP. Prospective data are provided concerning the common practice of using bicalutamide in this setting.


Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Azasteroides/uso terapêutico , Hormônio Liberador de Gonadotropina/uso terapêutico , Nitrilos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Compostos de Tosil/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Método Duplo-Cego , Dutasterida , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos
17.
Urology ; 85(3): 704.e9-14, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25733305

RESUMO

OBJECTIVE: To clarify the possible interference of the 5α-reductase inhibitor dutasteride with α-adrenergic blockers, whose action is mainly mediated by α1A-adrenergic receptor. METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Assuntos
Inibidores de 5-alfa Redutase/farmacologia , Azasteroides/farmacologia , Contração Muscular/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/fisiologia , Receptores Adrenérgicos alfa 1/efeitos dos fármacos , Animais , Dutasterida , Masculino , Contração Muscular/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa 1/fisiologia
18.
Urology ; 85(5): 1151-1155, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25770728

RESUMO

OBJECTIVE: To evaluate the clinical response and adverse events (AEs) of solifenacin (SOL) or mirabegron (MIR) in benign prostatic hyperplasia patients with persistent overactive bladder (OAB) symptoms after dutasteride (DUT) treatment. METHODS: Fifty cases with residual OAB symptom score (OABSS) ≥ 5 and OABSS Q3 ≥ 2 after at least 6 months treatment of DUT were included in this study. Patients were administered 5 mg/d of SOL (N = 25) or 50 mg/d of MIR (N = 25), and International Prostate Symptom Score (IPSS) and OABSS were prospectively collected at 4 and 12 weeks. The safety was evaluated by changes in postvoided residual urine volume and the incidence of AEs. RESULTS: After DUT administration, the mean prostate volume, IPSS, and OABSS were 39.0 mL, 17.6, and 8.1, respectively. SOL 5 mg significantly reduced the IPSS, OABSS, and OABSS Q3 at 4 and at 12 weeks (-3.1, -2.7, -1.3; P <.05); however, 4 patients could not continue the SOL treatment owing to AEs. All patients could continue the 12 weeks of MIR treatment, and MIR 50 mg reduced IPSS and OABSS at 4 weeks and reduced IPSS, OABSS, and the OABSS Q3 (-3.0, -2.5, -0.9; P <.05) at 12 weeks. Postvoided residual urine volume increased by ≥ 100 mL after treatment in 2 cases in the SOL group but not in any patient in the MIR group. CONCLUSION: Additional SOL or MIR might result in amelioration of the persistent OAB symptom after DUT treatment in patients with an enlarged prostate.


Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Acetanilidas/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Azasteroides/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Quinuclidinas/uso terapêutico , Tetra-Hidroisoquinolinas/uso terapêutico , Tiazóis/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Dutasterida , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Hiperplasia Prostática/complicações , Succinato de Solifenacina , Bexiga Urinária Hiperativa/etiologia
20.
Zhonghua Nan Ke Xue ; 21(1): 17-22, 2015 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-25707134

RESUMO

OBJECTIVE: To explore the molecular mechanism of dutasteride inhibiting fertility by studying its effects on the expressions of the epididymal epithelial junction proteins Claudin1 and ß-catenin in rats. METHODS: Sixteen 3-month-old SD male rats were equally divided into an experimental and a negative control group to be treated intragastrically with dutasteride at 40 mg/kg per day and the same dose of solvent, respectively, for 14 consecutive days. Then, the sperm motility and morphology of the rats were detected by computer-assisted sperm analysis, the serum levels of testosterone (T) and dihydrotestosterone (DHT) measured by ELISA, changes in the tight junction of epididymal cells observed under the transmission electron microscope, the protein and gene expressions of Claudin1 and ß-catenin determined by RT-PCR and immunohistochemistry, and the conception rate of the mated female rats calculated. RESULTS: Dutasteride significantly suppressed the serum DHT level, sperm motility, and fertility of the rats (P <0.05). Interspaces between epididymal epithelial cell tight junctions were observed, the volume of epididymal fluid obviously increased, and the expressions of Claudin1 and ß-catenin gene and protein remarkably downregulated in the experimental rats (P <0.05). CONCLUSION: Dutasteride can significantly inhibit the fertility of male rats by reducing the serum DHT level, suppressing Claudin1 and ß-catenin expressions, and damaging epididymal epithelial cell junctions.


Assuntos
Azasteroides/farmacologia , Claudina-1/metabolismo , Epididimo/efeitos dos fármacos , Agentes Urológicos/farmacologia , beta Catenina/metabolismo , Animais , Di-Hidrotestosterona/sangue , Dutasterida , Epididimo/metabolismo , Feminino , Fertilidade/efeitos dos fármacos , Humanos , Junções Intercelulares/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Motilidade Espermática/efeitos dos fármacos , Testosterona/sangue
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