5α-reductase Inhibitors Research Articles

Intraoperative floppy iris syndrome: an updated review of literature.

Intraoperative Floppy iris syndrome(IFIS) remains a challenge for surgeons during phacoemulsification. Initially, it was related to the use of tamsulosin, an alpha adrenergic receptor blocker used in benign prostatic hyperplasia. Subsequently, other alpha adrenergic receptor such as alfuzosin, terazosin and doxazosin alongwith different other class of medications and systemic risk factors were identified. Other class of medications includes 5-alpha reductase inhibitor, angiotensin receptor antagonist, benzodiazepines, antipsychotics and antidepressants. Other risk factors include increasing age, male gender, diabetes, hypertension and decreased preoperative pupil diameter. It is very important for surgeons to identify these risk factors preoperatively and take appropriate preoperative and intraoperative measures to tackle the dreaded complications of IFIS. Sometimes, it is important for an ophthalmologist to work in cooperation with physician and urologist to minimize the complications. In conclusion, awareness of the risk factors associated with IFIS, their detailed preoperative assessment and intraoperative measures and surgical intervention is crucial in addressing IFIS. Lack of awareness can turn a routine, uneventful surgery into one with significant visual morbidity.

Therapeutic effect of iodised serum milk protein, lycopene and their combination on benign prostatic hyperplasia induced in rats.

Benign prostatic hyperplasia (BPH) is a common chronic disease in ageing men. Synthetic inhibitors of 5α-reductase commonly used in BPH treatment have limited effectiveness and may cause side effects. Evaluation of iodised serum milk protein and lycopene therapeutic effect in rat BPH model was the aim of the present study. BPH was induced in male Wistar rats by surgical castration and subsequent testosterone administrations (25mg/kg, 7 injections). Rats with induced BPH received lycopene (5mg/kg), iodised serum milk protein (200µg/kg) or their combination for 1month daily. The efficacy of the treatment was evaluated by the prostate weight, prostatic index and ventral lobe epithelium thickness. In lycopene and iodised serum milk protein-treated rats, prostate weight and prostatic index were significantly reduced compared to control group; and lycopene and iodised serum milk protein used in combination yielded an additive effect. Thus, further investigation of combined supplementation with micronutrients and plant-derived substances in BPH models may help to find new opportunities or its safe and effective treatment.

Change in hair growth-related gene expression profile in human isolated hair follicles induced by 5-alpha reductase inhibitors - dutasteride and finasteride - in the presence of testosterone.

Change in hair growth-related gene expression profile in human isolated hair follicles induced by 5-alpha reductase inhibitors - dutasteride and finasteride - in the presence of testosterone.

Inhibitory Activities of Dimeric Ellagitannins Isolated from Cornus alba on Benign Prostatic Hypertrophy.

Benign prostatic hypertrophy (BPH) is an intractable chronic inflammatory disease. We studied the efficacy of two ellagitannins, namely camptothin B (1) and cornusiin A (2) that were isolated from Cornus alba (CA) for the treatment of BPH, which is a common health issue in older men. The ellagitannins (1 and 2) were evaluated on its inhibitory activities of the enzyme 5α-reductase and tumor necrosis factor (TNF)-α, its interleukin (IL)-1β, IL-6, and IL-8 production, and its anti-proliferation and apoptosis induction in prostate cells that show hypertrophy (RWPE-1 cell). In inhibition of 5α-reductase, the ellagitannins (1 and 2) showed potential effects, compared to the positive control, finasteride. In the case of IL-1β, IL-6, IL-8, and TNF-α, 1 and 2 showed good inhibitory effects as compared to the control group treated with LPS. The ellagitannins (1 and 2) were also shown to inhibit proliferation of, and induce apoptosis in, the RWPE-1 cell. These results suggest that the ellagitannins (1 and 2) may be good candidates for the treatment of BPH.

Clinical characteristics and oncological outcomes in negative multiparametric MRI patients undergoing robot-assisted radical prostatectomy.

Efforts are ongoing to try and find ways to reduce the number of unnecessary prostate biopsies without missing clinically significant prostate cancers (csPCa). The utility of multiparametric magnetic resonance imaging (mpMRI) in detecting prostate cancer (PCa) shows promise to be used as triage test for systematic prostate biopsy. Our aim is to Study clinical parameters and oncological outcomes in men with negative mpMRI (nMRI; PI-RADS v2 scores of ≤ 2) who underwent robot-assisted radical prostatectomy (RARP) to evaluate nMRI's practicality as a biopsy triage test. Retrospective analysis of 331 men with nMRI who underwent RARP between 2014 and 2020 compared with men with positive mpMRI (pMRI; PI-RADS v2 scores ≥ 3, N = 1770). csPCa was defined as Gleason score ≥ 3 + 4 and biochemical recurrence (BCR) was defined as PSA > 0.2 ng/ml on two occasions. Biopsies were graded with the International Society of Urologic Pathology [ISUP] grade. Descriptive statistics for nMRI and pMRI were performed. Mann-Whitney U test was used for continuous variables and χ 2 for categorical variables. Univariable and multivariable regression analyses were performed. Univariable analysis shows statistically significant difference (p < .05) between median age (nMRI-61 years vs. pMRI 63 years), race (higher incidence of nMRI in African American men), use of 5-alpha reductase inhibitors (higher rate in nMRI). While incidence rates of family history of PCa, suspicious digital rectal examination (DRE) findings, median PSA levels and 4Kscore, were lower in nMRI versus pMRI. Rates of positive surgical margins and BCR were comparable in nMRI versus pMRI. Biopsy ISUP Grades I and II upgraded by 51% and 12%, respectively in final pathology. African American race and no history of the prior negative biopsy were significant predictors for upgrading. Men with nMRI pose diagnostic challenges as they tend to be younger patients with lower rates of suspicious DRE findings and lower 4K scores, yet comparable oncological outcomes in csPCa rates, positive surgical margins, and BCR rates.

A phase 2 study of berzosertib (M6620) in combination with carboplatin compared with docetaxel in combination with carboplatin in metastatic castration-resistant prostate cancer.

5034 Background: Alterations in DNA damage repair (DDR) genes are common in metastatic castration-resistant prostate cancer (mCRPC), and are implicated in responses to carboplatin [carbo], PARP inhibitors and immunotherapeutics. Inhibitors of the ATR kinase, which is involved in the DDR response, have been demonstrated to have synergistic activity with platinum compounds in preclinical models. We therefore conducted a phase 2 study of the ATR inhibitor berzosertib [berzo]+carbo vs. docetaxel [doce]+carbo in mCRPC. Methods: Patients (pts) previously treated with at least one secondary hormonal therapy and taxane underwent mandatory pre-treatment biopsy and were randomized 1:1 to receive Arm A (doce 60 mg/m2 day 1 + carbo AUC 4 day 1) or Arm B (berzo 90 mg/m2 days 2,9 + carbo AUC 5 day 1) every 21 days. Pts randomized to Arm A who were not candidates for doce received carbo AUC 5 monotherapy. Stratification factors were 1) prior PARP inhibitor (yes vs. no) and 2) evaluable disease by RECIST 1.1 (yes vs. no). Pts on Arm A crossed over to Arm B (berzo+carbo) at the earlier of PSA or radiographic progression. The primary endpoint was overall response rate (ORR; PSA reduction by ≥ 50% or radiographic response by RECIST 1.1). Secondary endpoints included time to PSA progression, radiographic PFS (rPFS), PFS by PCWG3 criteria, and adverse events (AEs) in each arm. Planned enrollment was 136 pts (for 130 to be treated), with interim analysis for futility after 65 pts were treated. Results: 73 pts were randomized between 6/2019 and 7/2020; 34 pts were treated on Arm A (26 carbo+doce; 8 carbo alone) and 31 on Arm B. Median number of prior systemic therapies (excluding ADT, 5α-reductase inhibitors, 1st generation antiandrogens) was 4 (range 2-8). Median treatment duration was 3 cycles, and 4 pts in each arm discontinued for AEs. Grade 3 or higher treatment-related AEs (TrAE) were seen in 13(38%) pts in Arm A and 21(68%) in Arm B. Pts in Arm B had greater frequency of grade 3-4 thrombocytopenia (8[26%] vs. 3[9%]). 1 pt in Arm B had grade 5 sepsis attributed to study treatment. ORR was 15% in Arm A (5/34; 5/26[19%] in pts who received carbo+doce) and 0% in Arm B (0/31). 14 pts in Arm A crossed over, with no subsequent responses seen. Median rPFS was 2.1(95% CI:2.0,3.2) mo in Arm A and 2.4(1.9,4.2) mo in Arm B. At planned interim analysis, trial enrollment and crossover to Arm B were halted due to futility. Conclusions: Carbo+berzo led to fewer overall responses and a higher rate of grade 3 or higher TrAEs compared to carbo+doce. All responses seen were in pts who received carbo+doce despite requirement for prior progression on taxane, suggesting that this combination is favored over carbo+berzo or carbo monotherapy in a heavily pre-treated biomarker-unselected population. Extensive genetic and molecular studies for DDR assessment from tissue and cfDNA are in progress. Clinical trial information: NCT03517969.

The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder.

Opioid use disorder (OUD) has become a leading cause of death in the United States, yet current therapeutic strategies remain highly inadequate. To identify potential treatments for OUD, we screened a targeted selection of over 100 drugs using a recently developed opioid self-administration assay in zebrafish. This paradigm showed that finasteride, a steroidogenesis inhibitor approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia, reduced self-administration of multiple opioids without affecting locomotion or feeding behavior. These findings were confirmed in rats; furthermore, finasteride reduced the physical signs associated with opioid withdrawal. In rat models of neuropathic pain, finasteride did not alter the antinociceptive effect of opioids and reduced withdrawal-induced hyperalgesia. Steroidomic analyses of the brains of fish treated with finasteride revealed a significant increase in dehydroepiandrosterone sulfate (DHEAS). Treatment with precursors of DHEAS reduced opioid self-administration in zebrafish in a fashion akin to the effects of finasteride. These results highlight the importance of steroidogenic pathways as a rich source of therapeutic targets for OUD and point to the potential of finasteride as a new treatment option for this disorder.

Efficacy of Minoxidil Combined With Photobiomodulation for the Treatment of Male Androgenetic Alopecia. A Double-Blind Half-Head Controlled Trial.

Androgenetic alopecia (AGA) is a hair loss disorder that frequently affects the male population. Conventional treatment modalities are limited to minoxidil, 5α reductase inhibitors, and hair transplantation procedures. The efficacy of low-level laser therapy (LLLT), also known as photobiomodulation, in the treatment of AGA has been reported, yet little is known about the outcomes of combining photobiomodulation with other conventional therapies. To evaluate hair growth improvement in males with AGA, during the administration of minoxidil with and without photobiomodulation, using a half-head model. Twenty-one men with AGA agreed to undergo 12 minutes of low-level laser irradiation (using a modified Capellux®), followed by topical minoxidil application (1 mlof 5% solution), to the affected scalp two times per day for 6 months. The photobiomodulation devices were modified such that the left half emitted light, and the right half did not. Efficacy was assessed by blinded analyses of clinical photos and automated phototrichograms (Trichoscan®) taken before treatment and after 3 and 6 months of therapy. None of the study participants experienced any adverse events. All patients showed improvements in hair coverage on both sides of the scalp at 3 and 6 months. On the side with combined treatments, the number of total hairs was significantly increased after 3 (P < 0.001) and 6 months (P = 0.001). A similar increase was also observed on theminoxidil-only side, at both 3 (P < 0.001) and 6 months (P < 0.001). No statistically significant differences were detected between sides (P > 0.05). Additional improvement was not observed with the association of photobiomodulation to topical minoxidil in male AGA. Differences from previous studies that might have influenced our result includenon-collimated light source, higher dosimetry, and a cohort with darker skin phototype and more severe alopecia. Lasers Surg. Med. 2021. © 2021 Wiley Periodicals LLC.

A COST VARIATION ANALYSIS STUDY OF DRUGS USED IN THE MANAGEMENT OF BENIGN PROSTATIC HYPERPLASIA AVAILABLE IN THE INDIAN MARKET

Objectives: The objectives of the study are to evaluate the cost variation and cost ratio of different brands of the drugs used in the treatment of benign prostatic hyperplasia (BPH).&#x0D; Methods: The cost of alpha-blockers and 5 alpha-reductase inhibitors used in the treatment of BPH was noted from CIMS (Oct 2019–Jan 2020), Drugs Update, and Medline. The differences between the maximum and minimum cost of various brands of the same drug were analyzed and percentage variation in the cost was calculated. The results of the study were expressed in absolute numbers and percentages.&#x0D; Results: All the drugs used in the treatment of BPH are only available in tablet and capsule forms, in 10 different dosages and in 242 different brand names, of which 10 mg alfuzosin and 2.5 mg finasteride have the highest (518) and lowest (14) percentage of cost variation, while 0.4 mg tablet form of tamsulosin is available in the maximum number of brands-41.&#x0D; Conclusion: This pharmacoeconomic study reveals that there is wide variation in the cost of most of the drugs used in the treatment of BPH. Therefore, it is very much essential for both government and pharmaceutical companies to make combined efforts to reduce the cost of these drugs, which will reduce the economic burden on the patients and also reduce the overall health care costs.

Assessment of progesterone synthesis and its regulation role on dihydrotestosterone secretion in sheep epididymis.

Progesterone (P4) is an anti-androgen compound whose role in sperm maturation and functionality remains unclear in sheep. Here, we aimed to investigate the regulation mechanism of P4 on the epididymal secretion of dihydrotestosterone (DHT). To this end, we performed enzyme-linked immunosorbent assays, immunohistochemical staining, western blotting, and quantitative real-time polymerase chain reaction to detect P4 concentration as well as StAR, P450scc, and 3β-HSD expression in sheep epididymis. Besides, cauda epithelial cells were cultured at different concentrations of P4 (10-9-10-5 g ml-1) as well as with or without the P4 receptor (PGR) inhibitor RU486 (10-7 M) or the PI3K-AKT inhibitor LY294006 (10-7 M) to explore the effect of P4 on DHT secretion and the underlying regulatory mechanism. The results showed that the caput, corpus, and cauda of sheep epididymis could synthesize P4 but had different synthesis ability. The PGR expression levels were the highest in the cauda, followed by the corpus. In vitro cell culture showed that P4 inhibition of DHT secretion and 5α-reductase 1 and 2 expression in epididymal epithelial cells could be moderately mitigated by RU486 but not by LY294002. Our results indicated that the paracrine and autocrine P4 could affect the secretion of DHT in epididymal cells through PGR. Overall, this study provides new data regarding the involvement of P4 in sperm maturation and functionality in sheep.

Use of Topical Finasteride Vs Systemic Finasteride in Male Pattern Baldness

In this study we have analyzed the use of finasteride which is a type P-selective 5a-reductase inhibitor. By decreasing dihydroxytestestrone (DHT) level, it is found to be effective in the treatment of male androgenic alopecia. In this study, we compared the effect of topical vs. systemic finasteride in the treatment of androgenic alopecia. Our study is a randomized clinical trial study having 30 male patients. They have come for alopecia treatment at Nesam hospital, Coimbatore, India. We have selected male patients with androgenic alopecia and divided them into two groups (A, B), randomly having 15 patients in each group. For group A, Topical finasteride (0.1%) with minoxidil (5%) solution was given. Group B patients received topical minoxidil with oral finasteride (1mg) tablets. All patients were regularly followed up till the end of 6 months. A Patient had a first review in the first week followed by monthly follow up. Following parameters were taken into account: size of bald area, total hair count, and terminal hair. Data was analyzed by Chi-square statistical test. Each month the terminal hair, size of bald area and hair count between the two groups were compared. In the initial few months group, A showed good improvement. But Serial measurements indicated that a significant increase in hair counts and terminal hair counts is seen in both groups. This study showed that on long term follow-up of more than 3 months, both topical and systemic finasteride groups had similar results.

Frontal Fibrosing Alopecia: A Review.

Frontal fibrosing alopecia is a scarring alopecia, the prevalence of which is increasing worldwide since its first description in 1994. The reason for this emerging epidemic may be a higher exposure to an unknown trigger, although its aethiology and pathogenesis still remain enigmatic. Clinical, trichoscopic, sonographic, and histopathologic findings are allowing clinicians to understand more aspects about this type of cicatricial alopecia. Several treatments have been used in frontal fibrosing alopecia, although the 5-alpha reductase inhibitors seem to be the most promising. The aim of this report is to provide a compilation about the published data regarding frontal fibrosing alopecia in a narrative review.

Hong Kong Geriatrics Society and Hong Kong Urological Association consensus on personalised management of male lower urinary tract symptoms in the era of multiple co-morbidities and polypharmacy.

Lower urinary tract symptoms (LUTS) are common complaints of adult men. Benign prostatic hyperplasia (BPH) represents the most common underlying cause. As the incidence of BPH increases with age, and pharmacological treatment is a major part of the disease's management, the majority of patients with LUTS are managed by primary care practitioners. There are circumstances in which specialist care by urologists or geriatricians is required, such as failure of medical treatment, adverse effects from medical treatment, or complications from BPH. Referral choices can be confusing to patients and even practitioners in different specialties under such circumstances. There is currently no local consensus about the diagnosis, medical management, or referral mechanism of patients with BPH. A workgroup was formed by members of The Hong Kong Geriatrics Society (HKGS) and the Hong Kong Urological Association (HKUA) to review evidence for the diagnosis and medical treatment of LUTS. A consensus was reached by HKGS and HKUA on an algorithm for the flow of male LUTS care and the use of uroselective alpha blockers, antimuscarinics, beta-3 adrenoceptor agonists, and 5α-reductase inhibitors in the primary care setting. This consensus by HKGS and HKUA provides a new management paradigm of male LUTS.

Transurethral Resection of Prostate and Blood loss: Efficacy of Dutasteride in reducing perioperative blood loss.

Background: Benign Prostatic Hyperplasia (BPH) is the most common urological cause of urinary obstruction, affecting men above 50 years of age. Medical therapy used for managing BPH includes various medical regimes, including 5-alpha reductase inhibitors (5ARI), namely Dutasteride and more. The study aimed to evaluate the efficacy of four weeks' prior treatment with dutasteride on per-operative blood loss in patients of BPH undergoing transurethral resection of the prostate.&#x0D; Methodology: A prospective observational study was conducted from January to December 2019 at the Kidney Centre, Karachi, Pakistan. A total of 64 patients were included and divided into two groups. Group A patients were those who had been taking dutasteride (0.5 mg/day) for four weeks or more before surgery, and group B patients were not taking dutasteride drug before surgery. All patients underwent standard TURP, and the intra-operative blood loss was calculated. The collected data was analyzed using SPSS version 22.0.&#x0D; Results: In our study, there was a significantly less hemoglobin drop (1.2 gm vs. 2.2 gm) during prostate surgery in patients using dutasteride than those who were not using dutasteride.&#x0D; Conclusion: This study has revealed that the use of dutasteride four weeks before surgery significantly reduces intra-operative bleeding.

Three-Dimensional Proteome-Wide Scale Screening for the 5-Alpha Reductase Inhibitor Finasteride: Identification of a Novel Off-Target.

Finasteride, a 5-alpha reductase (5α-R) inhibitor, is a widely used drug for treating androgen-dependent conditions. However, its use is associated with sexual, psychological, and physical complaints, suggesting that other mechanisms, in addition to 5α-R inhibition, may be involved. Here, a multidisciplinary approach has been used to identify potential finasteride off-target proteins. SPILLO-PBSS software suggests an additional inhibitory activity of finasteride on phenylethanolamine N-methyltransferase (PNMT), the limiting enzyme in formation of the stress hormone epinephrine. The interaction of finasteride with PNMT was supported by docking and molecular dynamics analysis and by in vitro assay, confirming the inhibitory nature of the binding. Finally, this inhibition was also confirmed in an in vivo rat model. Literature data indicate that PNMT activity perturbation may be correlated with sexual and psychological side effects. Therefore, results here obtained suggest that the binding of finasteride to PNMT might have a role in producing the side effects exerted by finasteride treatment.

5α-Reductase Inhibitors Could Prevent the Clinical and Pathological Progression of Prostate Cancer: A Meta-analysis.

To explore the efficacy of 5-ARIs in PCA (Prostate Cancer). Searching through the major medical databases such as PubMed, Science Citation Index, EMBASE, Medline, Web of Science, Cochrane Library for all published studies in English until 2018. The following search terms were used: "Finasteride", "dutasteride", "5α reductase inhibitors", "5-ARIs", "prostate cancer", "prostate neoplasm" and the additional related studies were manually searched. Newcastle-Ottawa Scale (NOS) assessed the qualities of studies, and the outcome measures were observed by RR or OR with 95% CIs. We included 9 eligible studies for analyses from 2011 to 2017. We found that 5-ARIs group may have fewer progression (OR = 0.48 95%CI: 0.37-0.61 P < 0.00001, I2=4% p = 0.39) and lower pathological progression (OR = 0.46; 95%CI: 0.29-0.73; p = 0.001, I2=0% p = 0.45), compared with control groups. However, the OS did not show significant difference between two groups (OR=1.10; 95%CI:0.90-1.35; P = 0.35, I2 = 93% P < .00001 ). The use of 5-ARIs could prevent progression in PCA patients both clinical and pathological.

Cardiac and Brainstem Neuroinflammatory Pathways Account for Androgenic Incitement of Cardiovascular and Autonomic Manifestations in Endotoxic Male Rats.

Inconsistent reports are available on the role of testosterone in end-organ damage caused by endotoxemia. Here, pharmacologic, surgical, and molecular studies were employed to assess the testosterone modulation of cardiovascular, autonomic, and peripheral and central inflammatory derangements caused by endotoxemia. Studies were performed in conscious male rats preinstrumented with femoral indwelling catheters for the measurement of blood pressure and subjected to castration or pharmacologic interventions that interrupt the biosynthetic cascade of testosterone. Compared with the effects of lipopolysaccharide (10 mg/kg intravenously) in sham operated rats, 2-week castration reduced the lipopolysaccharide-evoked (1) falls in blood pressure, (2) decreases in time- and frequency-domain indices of heart rate variability, (3) shifts in spectral measures of cardiac sympathovagal balance toward parasympathetic dominance, and (4) increases in protein expressions of toll-like receptor-4 and monocyte chemoattractant protein-1 in heart and medullary neurons of the nucleus tractus solitarius and rostral ventrolateral medulla. While the ameliorating actions of castration on endotoxic cardiovascular manifestations were maintained after testosterone replacement, the concomitant inflammatory signals were restored to near-sham levels. The favorable influences of castration on inflammatory and cardiovascular abnormalities of endotoxemia were replicated in intact rats pretreated with degarelix (gonadotropin-releasing hormone receptor blocker) or finasteride (5α-reductase inhibitor) but not formestane (aromatase inhibitor). The data signifies the importance of androgens and its biosynthetic enzymes in cardiovascular and autonomic insults induced by the endotoxic inflammatory response. Clinically, the interruption of testosterone biosynthesis could offer a potential strategy for endotoxemia management.

Restorative effects of red onion (Allium cepa L.) juice on erectile function after-treatment with 5α-reductase inhibitor in rats.

Benign prostatic hyperplasia (BPH) is one of the most prevalent conditions among aged men. The use of 5α-reductase inhibitors (5-ARIs) to treat BPH was linked to erectile dysfunction (ED). Many medicinal plants and secondary metabolites are used in the management of ED. Onion (Allium cepa L.) is an economically affordable vegetable with vital phytochemicals and biological functions. The study aimed to identify the beneficial effects of onion juice on dutasteride (a 5-ARI)-induced ED. Rats were divided into two groups (n = 5 per group): control and dutasteride-treated rats (0.5 mg/kg/day). Dutasteride was administered in drinking water for 12 weeks. Experiments were performed at the end of the 12th week. In vivo erectile responses were measured before and after intracavernosal injection of onion. Relaxant responses to onion juice were examined in the corpus cavernosum (CC). Acetylcholine (ACh)-, electrical field stimulation (EFS)-, sodium nitroprusside (SNP)-induced relaxation responses in CC tissues were evaluated in the absence and presence of onion juice. Total intracavernosal pressure (ICP) and ICP/ mean arterial pressure were significantly reduced in dutasteride-treated rats (1881.14 ± 249.72 mmHg, P < 0.001;0.26 ± 0.03, P < 0.01) as compared to control rats (4542.60 ± 429.19 mmHg, 0.51 ± 0.05), which was normalized after the intracavernous administration of onion (3288.60 ± 185.45 mmHg, 0.58 ± 0.04). Onion markedly induced relaxant responses in control (72.5 ± 4.7) and dutasteride-treated (66.5 ± 2.7) groups after precontraction with phenylephrine. Relaxation responses to onion were partially inhibited after precontraction with KCl (32.5 ± 3.1, P < 0.001). The relaxant responses to ACh (14.9 ± 4.2, P < 0.01) were diminished in dutasteride-treated CC) compared to control CC(59.8 ± 3.4), which was enhanced after the incubation with onion (36.6 ± 4.8). There were no differences in relaxation response to SNP among all groups. However, relaxation response to SNP was reduced in dutasteride-treated CC at 1 μM(P < 0.05) and 10 μM dosages (P < 0.001), which was partially increased after the incubation with onion at 10 μM dosage (P < 0.01). The presence of onion did not change the reduction in EFS-caused relaxation in the dutasteride-treated group. The current data suggest that red onion juice has a restorative effect on erectile function and endothelium-dependent relaxation response following the treatment of dutasteride.

Highlights on Steroidal Arylidene Derivatives as a Source of Pharmacologically Active Compounds: A Review.

Steroids constitute a unique class of chemical compounds, playing an important role in physiopathological processes, and have high pharmacological interest. Additionally, steroids have been associated with a relatively low toxicity and high bioavailability. Nowadays, multiple steroidal derivatives are clinically available for the treatment of numerous diseases. Moreover, different structural modifications on their skeleton have been explored, aiming to develop compounds with new and improved pharmacological properties. Thus, steroidal arylidene derivatives emerged as a relevant example of these modifications. This family of compounds has been mainly described as 17β-hydroxysteroid dehydrogenase type 1 and aromatase inhibitors, as well as neuroprotective and anticancer agents. Besides, due to their straightforward preparation and intrinsic chemical reactivity, steroidal arylidene derivatives are important synthetic intermediates for the preparation of other compounds, particularly bearing heterocyclic systems. In fact, starting from arylidenesteroids, it was possible to develop bioactive steroidal pyrazolines, pyrazoles, pyrimidines, pyridines, spiro-pyrrolidines, amongst others. Most of these products have also been studied as anti-inflammatory and anticancer agents, as well as 5α-reductase and aromatase inhibitors. This work aims to provide a comprehensive overview of steroidal arylidene derivatives described in the literature, highlighting their bioactivities and importance as synthetic intermediates for other pharmacologically active compounds.

PROSTATOPROTECTIVE EFFECT OF MACLURA POMIFERA OIL EXTRACT AND THE WAY IT IS IMPLEMENTED

Relevance. In the experiment, it was shown that in rats with a sulpiride induced prostate hyperplasia (SGP) which was treated by the Maclura Pomifera oil extract (OEM), a prostatic index is normalized, biochemical indicators and morphofunctional state of the prostate are improved. However, the mechanism of implementing corrective influence remains unknown. Objective: to exam the contribution of hormonally mediated signaling pathways of the mechanism of pharmacological effect of oil extract in the form of rectal suppositories at the experimental hyperplasia of the prostate in rats. Materials and methods. On 60 rats of both sexes, acute toxicity of the active substance was studied with intragastric administration of OEM (dose on the active substance 5000 mg/kg, n = 12) or suppositories mass with OEM (dose for the active substance of 1500 mg/kg, n = 12). Under rectal administration, toxicity was investigated with the introduction of OEM (dose of the active substance 1000 mg/kg, n = 12) or suppositories mass with OEM (dose for the active substance 300 mg/kg, n = 12). A group of intact control amounted to 12 rats. The SGP model was created in rats (age 9-11 months, body mass 330-360 g, n = 18) by sulpiride (40 mg / kg, i.p., 30 days). The rats of the control group (n = 6) were obtained with 0.5 ml of 0.9% NaCl, i.m. From 31 to 51 days of the experiment, rats in the therapeutic mode were treated with OEM suppositories (380 mg/kg, n = 12) or a reference drag Prostaplant Forte (35 mg/kg, n = 6) once a day. The testosterone (Tc) and E2 content, level 5α-dihydrotestosterone (5α-DHT) were determined by the immunoferment method in serum. In the prostate homogenate, the content of 5α-reductase (5αR) was studied, as well as the concentration of androgenic (AR) and estrogenic (Erα) receptors. Results. Toxic influence on the internal organs and deaths of animals after the introduction of the maximum possible amounts of OEM was not observed. The use of suppositories with OEM in rats with SGP normalized the content of sex hormones. Significant inhibition of 5αR activity and a decrease in the content of AR, as well as an increase in the content of ERα, were detected. The group with the introduction of the Prostaplant forte was observed similar improvements. It was assumed that the implementation of the antiproliferative effect of the MEM is carried out due to the coexpression of the ERα and ERβ, which leads to the blocking of the ERα ability to react to the ligand (estrogen) and to a decrease in cell proliferation. Conclusions. 1. Extract of Maclura refers to the ІV class of toxicity with intragastric and rectal administration (low-toxic substances). 2. The use of suppositories with OEM in rats with SGPH normalizes the functional activity of the prostate, which is confirmed by the normalization of the content of sex hormones. 3. Extract of Maclura in the prostate cells inhibits 5α-reductase activity, reduces androgen receptors and the testosterone ratio/androgen receptors as the same to drugs with 5α-reductase inhibition action. 4. Phytosuppositories with OEM in a dose of 380 mg/kg do not inferior on the efficiency of the prostatoprotective action of the referens drag Prostaplant forte in a dose of 35 mg/kg.