scholarly journals Effect of sildenafil citrate on prediabetic and diabetic albino rats treated with metformin

2021 ◽  
Author(s):  
Ahmed mohmed Taha ◽  
Haredy Hassan Haredy ◽  
Ahmed Ghareip ◽  
Ahmed El sayed Nour El-deen ◽  
Yasser M Ashour
Keyword(s):  
Diabetic Complications ◽  
Initial Period ◽  
Pde5 Inhibitor ◽  
Cyclic Guanosine Monophosphate ◽  
Diabetic Rats ◽  
Guanosine Monophosphate ◽  
Sildenafil Citrate ◽  
Albino Rats ◽  
Epidemic Disease ◽  
Beneficial Effects

Diabetes Miletus (DM) is a global epidemic disease. It is estimated that there are already 415 million adults aged 20–79 years diabetics worldwide. Sildenafil citrate is a phosphodiesterase type 5 (PDE5) inhibitor, which increases cyclic guanosine monophosphate (cGMP) and metformin (MET) is a biguanide used for the treatment of type 2 diabetes which increases peripheral insulin sensitivity. Aim: This study aims to assess the effect of sildenafil citrate and metformin on lipid profile and glycemic control in diabetic and prediabetic albino rats. Materials and methods: Adult male albino rats are used and divided into nine groups each group consists of 10 rats, diabetes is induced by feeding a high-fat diet (HFD) for an initial period of 2 weeks followed by a single intraperitoneal injection of (35 mg/kg) Streptozotocin. Prediabetes is induced by feeding (HFD) and glucose in water for a period of 2 weeks. Sildenafil was given in a dose of (5 &10 mg/kg/day orally for 4 weeks), metformin was given in a dose of (50 &100 mg/kg/day orally for 4 weeks) using oral gavages to normal healthy rats, diabetic and prediabetic rats. Blood samples were collected after 4 weeks of treatment in all experimental groups. Results: Combined administration of sildenafil and metformin on diabetic rats improving hyperglycemia, oxidative stress, and hyperlipidemia induced by streptozotocin than the administration of metformin or sildenafil alone. Conclusion: Sildenafil has beneficial effects against some diabetic complications. The present study showed that sildenafil with metformin has beneficial effects against diabetic complications.

scholarly journals Angiotensin-(1-7) Downregulates Diabetes-Induced cGMP Phosphodiesterase Activation in Rat Corpus Cavernosum

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Gursev S. Dhaunsi ◽  
Mariam Yousif ◽  
Batoul Makki ◽  
Saghir Akhtar ◽  
Ibrahim F. Benter
Keyword(s):  
Gene Expression ◽  
Vascular Reactivity ◽  
Molecular Mechanisms ◽  
Corpus Cavernosum ◽  
Cyclic Guanosine Monophosphate ◽  
Diabetic Rats ◽  
Guanosine Monophosphate ◽  
Cgmp Phosphodiesterase ◽  
Beneficial Effects ◽  
Expression And Activity

Molecular mechanisms of the beneficial effects of angiotensin-(1-7), Ang-(1-7), in diabetes-related complications, including erectile dysfunction, remain unclear. We examined the effect of diabetes and/or Ang-(1-7) treatment on vascular reactivity and cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE) in corpus cavernosum. Male Wistar rats were grouped as (1) control, (2) diabetic (streptozotocin, STZ, treated), (3) control + Ang-(1-7), and (4) diabetic + Ang-(1-7). Following 3 weeks of Ang-(1-7) treatment subsequent to induction of diabetes, rats were sacrificed. Penile cavernosal tissue was isolated to measure vascular reactivity, PDE gene expression and activity, and levels of p38MAP kinase, nitrites, and cGMP. Carbachol-induced vasorelaxant response after preincubation of corpus cavernosum with PE was significantly attenuated in diabetic rats, and Ang-(1-7) markedly corrected the diabetes-induced impairment. Gene expression and activity of PDE and p38MAP kinase were significantly increased in cavernosal tissue of diabetic rats, and Ang-(1-7) markedly attenuated STZ-induced effects. Ang-(1-7) significantly increased the levels of nitrite and cGMP in cavernosal tissue of control and diabetic rats. Cavernosal tissue of diabetic rats had significantly reduced cGMP levels and Ang-(1-7) markedly prevented the STZ-induced cGMP depletion. This study demonstrates that attenuation of diabetes-induced PDE activity might be one of the key mechanisms in the beneficial effects of Ang-(1-7).

The nitric oxide–cGMP signaling pathway plays a significant role in tolerance to the analgesic effect of morphine

2011 ◽  
Vol 89 (2) ◽  
pp. 89-95 ◽  
Author(s):  
Ercan Ozdemir ◽  
Ihsan Bagcivan ◽  
Nedim Durmus ◽  
Ahmet Altun ◽  
Sinan Gursoy
Keyword(s):  
Nitric Oxide ◽  
Analgesic Effect ◽  
Soluble Guanylate Cyclase ◽  
Morphine Tolerance ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Albino Rats ◽  
Tail Flick ◽  
Analgesic Effects ◽  
Cgmp Signaling

Although the phenomenon of opioid tolerance has been widely investigated, neither opioid nor nonopioid mechanisms are completely understood. The aim of the present study was to investigate the role of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway in the development of morphine-induced analgesia tolerance. The study was carried out on male Wistar albino rats (weighing 180–210 g; n = 126). To develop morphine tolerance, animals were given morphine (50 mg/kg; s.c.) once daily for 3 days. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), BAY 41-2272, S-nitroso-N-acetylpenicillamine (SNAP), NG-nitro-l-arginine methyl ester (L-NAME), and morphine were considered at 15 or 30 min intervals (0, 15, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests (n = 6 in each study group). The results showed that YC-1 and BAY 41-2272, a NO-independent activator of soluble guanylate cyclase (sGC), significantly increased the development and expression of morphine tolerance, and L-NAME, a NO synthase (NOS) inhibitor, significantly decreased the development of morphine tolerance. In conclusion, these data demonstrate that the nitric oxide–cGMP signal pathway plays a pivotal role in developing tolerance to the analgesic effect of morphine.

scholarly journals Aphrodisiac Activity of Eulophia macrobulbon Extract on Erectile Dysfunction in Male Aged Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Watcharaporn Preedapirom ◽  
Kanokwan Changwichit ◽  
Piyarat Srisawang ◽  
Kornkanok Ingkaninan ◽  
Pornnarin Taepavarapruk
Keyword(s):  
Erectile Dysfunction ◽  
Serum Testosterone ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Sildenafil Citrate ◽  
Male Rats ◽  
Cgmp Level ◽  
Seminiferous Tubules ◽  
Aged Rats ◽  
Sexual Performance

This study investigated the effect of Eulophia macrobulbon (EM) extract on sexual performance in aged-related erectile dysfunction (ED) rats. The ethanol EM extract at the doses of 15, 150, and 450 and sildenafil citrate at the dose of 5 mg/kg body weight (BW) were administered orally to the aged male rats once daily for 21 days. Mating parameters and intracavernosal pressure (ICP) were measured to evaluate their sexual and erection functions. Numbers of sperm and sperm motility as well as the diameter of seminiferous tubules were observed. The serum testosterone and 3’,5’-cyclic guanosine monophosphate (cGMP) concentration in the rat penile tissue were analyzed. The results showed the significant increased sexual motivation, copulatory performance, and ICP of aged rats treated with sildenafil citrate and all doses of EM extract as compared to control aged rats. Moreover, their serum testosterone levels were slightly increased and significant increase in penile cGMP concentration was observed in these aged rats treated with sildenafil citrate and EM extract. The results suggest that treatment with EM could inhibit activity of PDE5 in penile tissue resulting in the increased cGMP level and bring to the improvement of erectile function and sexual performance.

scholarly journals L-Arginine Supplementation in Type II Diabetic Rats Preserves Renal Function and Improves Insulin Sensitivity by Altering the Nitric Oxide Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Taylor Claybaugh ◽  
Sarah Decker ◽  
Kelly McCall ◽  
Yuriy Slyvka ◽  
Jerrod Steimle ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Renal Dysfunction ◽  
Cell Damage ◽  
Cyclic Guanosine Monophosphate ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Rats ◽  
Guanosine Monophosphate ◽  
No Production ◽  
Type Ii

Rat studies demonstrated that type II diabetes mellitus (T2DM) decreases both the production and bioavailability of nitric oxide (NO). L-arginine (LA) provides the precursor for the production of NO. We hypothesized that LA dietary supplementation will preserve NO production via endothelial nitric oxide synthase (eNOS) causing renal microvascular vasodilation and increased glomerular blood flow and thus increasing glomerular filtration rate (GFR). This would impede the formation of reactive oxygen species which contributes to cell damage and death. LA supplementation preserved GFR in the treated diabetic rats compared to untreated diabetic rats. We provide evidence that this effect may be due to increased levels of eNOS and urinary cyclic guanosine monophosphate, which leads to renal microvascular vasodilation. Plasma nitrotyrosine was decreased in the LA treated rats; however, plasma nitrite levels remained unaffected as expected. Marked improvements in glucose tolerance were also observed in the LA treated diabetic rats. These results demonstrate that LA supplementation preserves NO activity and may delay the onset of insulin resistance and renal dysfunction during hyperglycemic stress. These results suggest the importance of the NO pathway in consequent renal dysfunction and in the development of insulin resistance in diabetic rats.

scholarly journals New Approaches in Oncology for Repositioning Drugs: The Case of PDE5 Inhibitor Sildenafil

2021 ◽  
Vol 11 ◽  
Author(s):  
Marian Cruz-Burgos ◽  
Alberto Losada-Garcia ◽  
Carlos D. Cruz-Hernández ◽  
Sergio A. Cortés-Ramírez ◽  
Ignacio Camacho-Arroyo ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Pde5 Inhibitor ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Systemic Hypertension ◽  
Pde5 Inhibitors ◽  
Development Costs ◽  
Cgmp Signaling ◽  
Molecular Effects ◽  
Approved Drugs

The use of already-approved drugs to treat new or alternative diseases has proved to be beneficial in medicine, because it reduces both drug development costs and timelines. Most drugs can be used to treat different illnesses, due their mechanisms of action are not restricted to one molecular target, organ or illness. Diverging from its original intent offers an opportunity to repurpose previously approved drugs to treat other ailments. This is the case of sildenafil (Viagra), a phosphodiesterase-5 (PDE5) inhibitor, which was originally designed to treat systemic hypertension and angina but is currently commercialized as erectile dysfunction treatment. Sildenafil, tadalafil, and vardenafil are PDE5 inhibitors and potent vasodilators, that extend the physiological effects of nitric oxide and cyclic guanosine monophosphate (cGMP) signaling. Although most of the biological implications of these signaling regulations remain unknown, they offer a large therapeutic potential for several diseases. In addition, some PDE5 inhibitors’ molecular effects seem to play a key role in different illnesses such as kidney disease, diabetes mellitus, and cancer. In this review, we discuss the molecular effects of PDE5 inhibitors and their therapeutic repurposing in different types of cancer.

scholarly journals Nitric oxide — soluble guanylate cyclase — cyclic guanosine monophosphate signaling pathway in the pathogenesis of heart failure and search for novel therapeutic targets

2021 ◽  
Vol 20 (6) ◽  
pp. 3035
Author(s):  
Zh. D. Kobalava ◽  
P. V. Lazarev
Keyword(s):  
Heart Failure ◽  
Signaling Pathway ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Severe Disease ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Phase Iii ◽  
Beneficial Effects ◽  
Stimulation Of

Heart failure is a severe disease with an unfavorable prognosis, which requires intensification of therapy and the search for novel approaches to treatment. In this review, the physiological significance of soluble guanylate cyclase-related signaling pathway, reasons for decrease in its activity in heart failure and possible consequences are discussed. Pharmacological methods of stimulating the production of cyclic guanosine monophosphate using drugs with different mechanisms of action are considered. Data from clinical studies regarding their effectiveness and safety are presented. A promising approach is stimulation of soluble guanylate cyclase, which showed beneficial effects in preclinical studies, as well as in the recently completed phase III VICTORIA study.

scholarly journals Multifunctional Isosteric Pyridine Analogs-Based 2-Aminothiazole: Design, Synthesis, and Potential Phosphodiesterase-5 Inhibitory Activity

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 902
Author(s):  
Abdel Haleem M. Hussein ◽  
Ahmed A. Khames ◽  
Abu-Bakr A. El-Adasy ◽  
Ahmed A. Atalla ◽  
Mohamed Abdel-Rady ◽  
...  
Keyword(s):  
Pde5 Inhibitor ◽  
Docking Study ◽  
Cyclic Guanosine Monophosphate ◽  
Molecular Shape ◽  
Guanosine Monophosphate ◽  
Molecular Docking Study ◽  
Reference Drug ◽  
Arterial Blood ◽  
Severe Hypotension

The elaboration of new small molecules that target phosphodiesterase enzymes (PDEs), especially those of type 5 (PDE5), is an interesting and emerging topic nowadays. A new series of heterocycle-based aminothiazoles were designed and synthesized from the key intermediate, 3-oxo-N-(thiazol-2-yl)butanamide (a PDE5 inhibitor that retains its amidic function), as an essential pharmacophoric moiety. The PDE5 inhibitors prevent the degradation of cyclic guanosine monophosphate, thereby causing severe hypotension as a marked side effect. Hence, an in vivo testing of the target compounds was conducted to verify its relation with arterial blood pressure. Utilizing sildenafil as the reference drug, Compounds 5, 10a, and 11b achieved 100% inhibitions of PDE5 without significantly lowering the mean arterial blood pressures (115.95 ± 2.91, 110.3 ± 2.84, and 78.3 ± 2.57, respectively). The molecular docking study revealed that the tested compounds exhibited docking poses that were similar to that of sildenafil (exploiting the amide functionality that interacted with GLN:817:A). The molecular shape and electrostatic similarity revealed a comparable physically achievable electrostatic potential with the reference drug, sildenafil. Therefore, these concomitant results revealed that the tested compounds exerted sildenafil-like inhibitory effects (although without its known drawbacks) on blood circulation, thus suggesting that the tested compounds might represent a cornerstone of beneficial drug candidates for the safe treatment for erectile dysfunction.

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