Effects and mechanisms of action of sildenafil citrate in human chorionic arteries

Objectives Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. Study Design Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. Results Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. Conclusion Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO

Conglomerateness: Size and Monopoly Control

The aim of this study is to evaluate the effects of sildenafil citrate on cisplatin-induced ovarian toxicity. Thirty-two female rats were divided into four groups. Group 1: saline control; group 2: cisplatin; group 3: sildenafil citrate; and group 4: cisplatin plus sildenafil citrate group. In groups 2 and 4, the rats were injected with 5 mg/kg cisplatin intraperitoneally (i.p.). In groups 3 and 4, the rats were injected with 1.4 mg/kg sildenafil citrate i.p. The ovaries were removed two weeks later in all groups. Histopathologic examination, follicle counting and classification were performed. The expression of anti-Mullerian hormone (AMH) was detected immunohistochemically in the ovarian tissues. Sildenafil alleviated cisplatin-induced histopathological changes in the ovarian tissue. Primordial, secondary and tertiary follicles were diminished in group 2 compared with group 1 (p <0.05). Pretreatment with sildenafil citrate preserved primordial follicle count in group 4 compared with group 2, and the difference was statistically significant (p <0.05). According to our results, immunoreactivity intensity of AMH was lower in group 2 compared with group 1 (92.4 +/- 3.97 versus 88.8 +/- 1.77) but not significantly, whereas immunoreactivity intensity of AMH was higher in group 4 compared with group 2 (88.8 +/- 1.77 versus 94.1 +/- 2.36; p<0.05). Our results demonstrated that pretreatment with sildenafil citrate is beneficial for protecting the ovaries from cisplatin-induced damage. Sildenafil citrate can be a choice for fertility preservation

Ventricular tachycardia after administration of sildenafil citrate: a case report

<p>Abstract</p> <p>Background</p> <p>It has not previously been reported that sildenafil citrate causes malignant arrhythmias in humans.</p> <p>Case presentation</p> <p>A 41-year-old man developed sustained ventricular tachycardia following sildenafil citrate administration.</p> <p>Conclusion</p> <p>It cannot be dismissed that this patient experienced ventricular tachycardia as an adverse effect of sildenafil citrate administration.</p

Haematological changes and wound healing effects of sildenafil citrate in diabetic albino rats

This study presents baseline data on the effect of sildenafil citrate on some of the haematological and biochemical parameters in wistar rats with diabetes and wound formation. Forty two albino rats weighing between 139 and 225 g were separated at random into seven groups (A, B, C, D, E, F and G) of six rats per group. Type 1 diabetes mellitus was induced in groups A, B, C and D by a single intra-peritoneal injection of 130 mg/kg Alloxan. Rats in group A were treated with orally dose of 50 mg/kg sildenafil citrate for 21 days and rats in group B were administered 10 IU of insulin intramuscularly once and sildenafil citrate as in Group A. The rats in group C were treated with a single dose of 10 IU of insulin intramuscularly, and rats in group D with only distilled water. Groups E and F were normal rats with wounds similar to those of diabetic rats in the previous groups and each rat in group E was also treated with sildenafil citrate as in Group A and those in group F were treated with only distilled water. Group G were normal rats without wound treated with sildenafil citrate as in Group A. Blood samples were taken before (day 0) and after the administration of the sildenafil citrate on day 7, 14 and 21. The results of the study showed significant decreased in red blood cells count from 6.28 ± 0.46 × 106 to 2.81 ± 0.46 × 106 in diabetic rats during the 14 days of treatment with sildenafil citrate, however, there was an indication that continues treatment for up to 21 days reduced the blood glucose and increased the red blood cells count and this may be an indication that sildenafil citrate improves insulin mediated glucose pathways.Keywords: Diabetes, Haematological parameters, Rats, Red blood cells, Sildenafil citrat

UV-ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF DAPOXETINE HYDROCHLORIDE AND SILDENAFIL CITRATE IN TABLET DOSAGE FORM

Objective: The objective of this research was to develop and validate a simple ultraviolet (UV) spectrophotometric method for simultaneous determination of sildenafil citrate and dapoxetine hydrochloride in a pharmaceutical formulation.Methods: Two simple UV spectrophotometric methods have been developed for simultaneous determination of sildenafil citrate and dapoxetine hydrochloride. For both methods, stock solutions were prepared in methanol followed by the further required dilutions with methanol. Proposed dual-wavelength method and ratio derivative method, the wavelength of maximum absorption for sildenafil citrate and dapoxetine hydrochloride was 292 nm and 231 nm, respectively.Results: In both methods, the linearity range lies between 10 and 60 μg/ml for sildenafil citrate and 2–12 μg/mL for dapoxetine hydrochloride with their respective wavelengths. By dual-wavelength method, the percentage of sildenafil citrate and dapoxetine hydrochloride was found to be 101.3% and 100.3%, respectively.Conclusion: Result obtained in this research work clearly indicated that both these methods were found to be accurate, precise, stable, and robust as indicated by low values of percentage relative standard deviation. Thus, the present study gives an excellent method for the determination of both the drugs in combined tablet formulation

Validasi Metode Identifikasi Sildenafil Sitrat, Tadalafil dan Fenilbutazon dalam Jamu Obat Kuat Secara Kromatografi Lapis Tipis – Densitometri

Jamu/Herbal Medicine that contain chemical compounds/Pharmaceutical compounds has been banned by The National Agency of Drug and Food Control in Indonesia, but in December 2017, BPOM released a public warning about aphrodisiac herbal medicine that contain chemical compound like sildenafil citrate and phenylbutazone in the market. The aim of this study was to find out the valid method for identification of sildenafil citrate and phenylbutazone in aphrodisiac herbal medicine. In this study, the developed method was applied to 22 brands of aphrodisiac herbal medicine sample. Sample was extracted with methanol, then 5 µl of sample spotted on silica gel plate 60 F 254 and eluated by chloroform : methanol : amonia (70 : 3 : 1.5, v/v/v). The spots were analyzed by TLC scanner at λ 286 nm. Sildenafil citrate was appeared at Rf 0.76; tadalafil at 0.6 and phenylbutazone at Rf 0.12 with resolution (Rs) value of sildenafil and tadalafil was 1.1 meanwhile tadalafil and phenylbutazone was 5.4. Limit of detection of sildenafil citrate was 8.552 µg/ml (2.053 mg/600 mg capsul), tadalafil was 1.629 µg/ml (0.391 mg/600 mg capsul), and phenylbutazone was 7.877 µg/ml (1.890 mg/600 mg capsul). This study found 14 brands that gave a positive result containing sildenafil citrate and no sample contain tadalafil and phenylbutazone

VALIDASI METODE KLT-DENSITOMETRI UNTUK ANALISIS SILDENAFIL SITRAT DALAM SUPLEMEN KESEHATAN STAMINA PRIA

VALIDATION OF THIN LAYER CHROMATOGRAPHY-DENSITOMETRY FOR ANALYSIS OF SILDENAFIL CITRATE IN MEN’S HEALTH SUPPLEMENTS STAMINA Ririz Yudha Zuhriyah Sildenafil citrate is a chemical drug which is forbidden by National Agency of Food and Drug Control (BPOM) to be added into men’s health supplements stamina. Recently, some men’s health supplements stamina had been found containing sildenafil citrate by BPOM. The aim of this study is to validate a TLC-Densitometry method used in the quantitative analysis of sildenafil citrate. Validation of the method that were determined i.e., selectiviy, detection limit, quantitation limit, linearity, accuracy and precision. A good solvent for extracting sildenafil citrate from matrix sample is methanol. Sildenafil citrate was separated from matrix’s component on silica gel F 254 using MeOH-EA (1:2) v/v as eluent. Retardation factor (Rf) of sildenafil citrate was 0.41, resolution factor between sildenafil citrate and the nearest matrix compound was 3.0. Sildenafil citrate spectrum showed maximum wavelength at 304 nm. The respond was to be linear at the range of sildenafil citrate concentration 500-1500 ppm. Linearity test results given linear correlation 0.9989 and Vxo 2.02% . The result showed that the detection limit of sildenafil citrate was 4.96 and quantitation limit was 15.03 ppm. Recovery of sildenafil citrate were found 98.46-101.09% with average of 99.83% and the precision result was 0.99%. Therefore, this method can be used for quantitative analysis of sildenafil citrate as the parameters of validation has meet the requirement. Keywords : Sildenafil Citrate, TLC-Densitometry, validation metho

The effects of sildenafil ciltrate on the lateral geniculate body of adult Wistar rats (Rattus norvegicus)- A histological study

The histological effect of oral administration of sildenafil citrate (Viagra), commonly used as an aphrodisiac and for the treatment of erectile dysfunction on one of the visual relay centres namely the lateral geniculate body (LGB) of adult Wistar rat was carefully studied. The rats of both sexes (n=24), average weight of 202g were randomly assigned into three treatment (n=18) and control (n=6) groups. The rats in the treatment groups ‘A’, ‘B’ and ‘C’ received respectively, 0.25mg/kg, 0.70mg/kg and 1.43mg/kg body weight of sildenafil citrate base dissolved in distilled water daily for 30 days, through orogastric feeding tube, while that of the control group D, received equal volume of distilled water daily during the period of the experiment. The rats were fed with growers’ mash obtained from Edo Feeds and Flour Mill Ltd, Ewu, Edo State, Nigeria and were given water liberally. The rats were sacrificed on day thirty-one of the experiment. The lateral geniculate body (LGB) was carefully dissected out and quickly fixed in 10% formal saline for histological studies. The histological findings after H&E method indicated that the treated section of the lateral geniculate body (LGB) showed some varying degree of reduced cellular population based on its sparse distribution, degenerative changes, cellular hypertrophy, and intercellular vacuolations appearing in the stroma. Varying dosage and long administration of sildenafil citrate may have some deleterious effects on the neurons of the intracranial visual relay centre and this may probably have some adverse effects on visual sensibilities by its deleterious effects on the cells of the lateral geniculate body (LGB) of adult Wistar rats. It is therefore recommended that further studies aimed at corroborating these observations be carried out

Protective effect of sildenafil citrate on contralateral testis injury after unilateral testicular torsion/detorsion

OBJECTIVES: This study was designed to investigate prevention of contralateral testicular injury with sildenafil citrate after unilateral testicular torsion/detorsion. METHODS: Thirty-seven adult male rats were divided into four groups: sham operated (group 1, n = 7), torsion/detorsion + saline (group 2, n = 10), torsion/detorsion + 0.7 mg of sildenafil citrate (group 3, n = 10) and torsion/detorsion + 1.4 mg of sildenafil citrate (group 4, n = 10). Unilateral testicular torsion was created by rotating the right testis 720º in a clockwise direction for 2 h in other groups, except for group 1, which was served as sham group. After torsion (2 h) and detorsion (2 h) periods, rats were killed. RESULTS: The level of reduced glutathion (GSH) (p<0.05) and the activities of catalase (p<0.01) and glutathione peroxidase (p<0.05) in the contralateral testis from group 2 were significantly lower and nitric oxide (NO) (p<0.05) level in the contralateral testis were significantly higher than those of group 1. Administration of low-dose sildenafil citrate (group 3) prevented the increases in malondialdehyde and NO levels and decreases in glutathione peroxidase activities and GSH values induced by testicular torsion. However, administration of high-dose sildenafil citrate (group 4) had no effect on these testicular parameters (p>0.05). Histopathological changes were detected in groups 2, 3 and 4. CONCLUSION: These results suggest that biochemically and histologically torsion/detorsion injury occurs in the contralateral testis following 2-h torsion and 2-h detorsion and that administration of low-dose sildenafil citrate before detorsion prevents ischemia/reperfusion cellular damage in testicular tissue