Tirotoksikoz nedenli erektil disfonksiyon üzerine sildenafil etkisinin histopatolojik olarak değerlendirilmesi
Öz
Amaç: Tirotoksikoz, periferik kan ve dokulardaki tiroit hormonu fazlalığından kaynaklı tüm klinik tabloları karşılayan bir çatı terimdir. Tirotoksikoz tablosu birçok organ ve metabolik süreci olumsuz yönde etkilemektedir. Bunlardan biri de erkek üreme sistemidir. Bu deneysel çalışmada tirotoksikoz nedenli erektil disfonksiyonda sildenafil tedavisinin disfonksiyonu önleyebilme etkisinin histopatolojik olarak değerlendirilmesi amaçlanmıştır.
Gereç ve Yöntem: Her biri 8 sıçandan oluşan 4 çalışma grubu oluşturuldu. Bu deneysel gruplar; Kontrol, Tirotoksikoz (Deney grubu), Tirotoksikoz + sildenafil uygulanan grup (Tedavi grubu) ve Tirotoksikoz oluşturulan + sildenafil çözücü solüsyon uygulanan grup (plasebo) grubu şeklindedir. Tirotoksikoz grubu erkek sıçanlara 0,2 mg/kg/gün dozunda ile 7 gün boyunca L-tiroksin enjekte edildi. Tedavi grubuna ise L- tiroksin uygulamasını takiben 10 mg/kg/gün dozda sildenafil, 24 gün boyunca intraperitoneal olarak uygulandı. Deneysel model tamamlanınca penis dokusu histokimyasal ve immünohistokimyasal incelemeler için %4’lük paraformaldehit içine alındı. Rutin immünohistokimyasal takip ve boyamalar yapılarak tüm örnekler ışık mikroskobunda değerlendirildi.
Bulgular: Deney grubuna ait deneklerde kavernöz boşluklarda dejenerasyon, daralma ve endotel hücrelerinde kayıp olduğu saptandı. Fibroelastik bağ doku ve düz kas dağılımı açısından tirotoksikoza maruz kalan sıçanlarda elastik lifler ve düz kaslarda belirgin azalma, kollajen liflerde ise artış olduğu saptandı. Tedavi grubunda tunica albuginea, corpus cavernosum, venöz sinüsler, kavernozal trabeküler düz kas ve ince fibröz bağ doku normal histolojik yapıya yakın olduğu görüldü. Kavernöz cisimlerin çapları istatistiksel olarak anlamlı bulundu (p<0,001). Kavernöz yapılarda fibrozis, dejenerasyon ve daralma sonuçlarında benzer farklılıklar gözlenmiştir.
İkili analizlere göre kontrol- tedavi ve deney- plasebo grupları arasındaki farklılıklar istatistiksel olarak anlamlı değilken, diğer tüm ikili farklılıklar anlamlı bulunmuştur (p<0,05). Periferik sinir dejenerasyonu açısından ise sadece kontrol grubunun deney ve plasebo grubu ile olan farklılıkları anlamlı bulundu (p<0,05).
Sonuç: Deneysel tirotoksikoz modelinin penil kavernöz dokuda histolojik hasara neden olduğu tespit edilmiştir. Ekzojen sildenafil uygulamasının histopatolojik olarak dejeneratif etkileri azalttığı saptanmıştır.
Anahtar Kelimeler
Kaynakça
- Moon JH, Yi KH. The Diagnosis and Management of Hyperthyroidism in Korea: Consensus Report of the Korean Thyroid Association. Endocrinol Metab. 2013; 28 (4): 275.
- Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct 1; 26 (10): 1343–421.
- Bahn RS, Burch HB, Cooper DS, Garber JR, Carol Greenlee M, Klein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: Management guidelines of the american thyroid association and American association of clinical endocrinoloigists. Endocr Pract. 2011 May 1; 17 (3): 456–520.
- Carani C, Isidori AM, Granata A, Carosa E, Maggi M, Lenzi A, et al. Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients. J Clin Endocrinol Metab. 2005 Dec; 90 (12): 6472–9.
- Krassas GE, Poppe K, Glinoer D. Thyroid Function and Human Reproductive Health. Endocr Rev. 2010 Oct 1; 31 (5): 702–55.
- Patel N, Kashanian J. Thyroid Dysfunction and Male Reproductive Physiology. Semin Reprod Med. 2016 Oct 14;34(06):356–60.
- Gong B, Ma M, Xie W, Yang X, Huang Y, Sun T, et al. Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis. Int Urol Nephrol. 2017 Oct 1; 49 (10): 1731–40.
- Scaglione F, Donde S, Hassan TA, Jannini EA. Phosphodiesterase Type 5 Inhibitors for the Treatment of Erectile Dysfunction: Pharmacology and Clinical Impact of the Sildenafil Citrate Orodispersible Tablet Formulation. Clin Ther. 2017 Feb 1; 39 (2): 370–7.
- Makay O, Yenisey C, Icoz G, Genc Simsek N, Ozgen G, Akyildiz M, Yetkin E. The role of allopurinol on oxidative stress in experimental hyperthyroidism. J Endocrinol Invest. 2009 Sep; 32 (8): 641-6.
- Çekmen, M. B., Turgut, M., Türköz, Y., Aygün, A. D., & Gözükara, E. M. Nitrik Oksit (NO) ve Nitrik Oksit Sentaz (NOS)'ın Fizyolojik ve Patolojik Özellikleri. Turkiye Klinikleri Journal of Pediatrics, 2001; 10 (4), 226-235.
- Thomas, D., et al. The chemical biology of nitric oxide: implications in cellular signaling. Free Radical Biology and Medicine, 2008, 45.1: 18-31.
- Bianchi G, Solaroli E, Zaccheroni V, Grossi G, Bargossi AM, Melchionda N, et al. Oxidative stress and anti-oxidant metabolites in patients with hyperthyroidism: Effect of treatment. Horm Metab Res. 1999; 31 (11): 620–4.
- Venditti, P., et al. Effect of thyroid state on lipid peroxidation, antioxidant defences, and susceptibility to oxidative stress in rat tissues. Journal of Endocrinology, 1997, 155: 151-157.
- Makay, B., et al. The interaction of oxidative stress response with cytokines in the thyrotoxic rat: is there a link?. Mediators of inflammation, 2009, 2009.
- Goldstein, A. M. B., et al. New observations on microarchitecture of corpora cavernosa in man and possible relationship to mechanism of erection. Urology, 1982, 20.3: 259-266.
- Costa WS, Carrerete FB, Horta WG, Sampaio FJB. Comparative analysis of the penis corpora cavernosa in controls and patients with erectile dysfunction. BJU Int. 2006 Mar; 97 (3): 567–9.
- Burnett, A. L., et al. Nitric oxide: a physiologic mediator of penile erection. Science, 1992, 257.5068: 401-403.
- Bassenge E. Coronary vasomotor responses: Role of endothelium and nitrovasodilators. Cardiovasc Drugs Ther. 1994 Aug; 8 (4): 601–10.
- Andersson KE, Wagner G. Physiology of penile erection. Physiol Rev. 1995; 75 (1): 191.
- Gur S, Kadowitz PJ, Gurkan L, Chandra S, Dewitt SY, Harbin A, et al. Chronic inhibition of nitric-oxide synthase induces hypertension and erectile dysfunction in the rat that is not reversed by sildenafil. BJU Int. 2010 Jul; 106 (1): 78–83.
- Ferraz, M., et al. The effects of sildenafil after chronic L-NAME administration in male rat sexual behavior. Pharmacology Biochemistry and Behavior, 2016, 146: 13-20.
- Cashen DE, MacIntyre DE, Martin WJ. Effects of sildenafil on erectile activity in mice lacking neuronal or endothelial nitric oxide synthase. Br J Pharmacol. 2002; 136 (5): 693–700.
- Salonia A, Castagna G, Saccà A, Ferrari M, Capitanio U, Castiglione F, et al. Is Erectile Dysfunction a Reliable Proxy of General Male Health Status? The Case for the International Index of Erectile Function-Erectile Function Domain. J Sex Med. 2012; 9 (10): 2708–15.
- Rajfer J, Aronson WJ, Dorey FJ, Bush PA, Ignarro LJ. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med. 1992 Jan 9; 326 (2): 90–4. 25. Försterrmann, U., et al. Isoforms of nitric oxide synthase: functions in the cardiovascular system.
- European heart journal, 1993, 14: 10-15. 26. Ahn, G. J., et al. Increased expression of the nitric oxide synthase gene and protein in corpus cavernosum by repeated dosing of udenafil in a rat model of chemical diabetogenesis. Asian journal of andrology, 2009, 11.4: 435.
- Angulo J, González-Corrochano R, Cuevas P, Fernández A, Fuente JML, Rolo F, et al. Diabetes exacerbates the functional deficiency of NO/cGMP pathway associated with erectile dysfunction in human corpus cavernosum and penile arteries. J Sex Med. 2010; 7: 758–68.
- Tuncayengin A, Biri H, Onaran M, Şen I, Tuncayengin Ö, Polat F, et al. Cavernosal tissue nitrite, nitrate, malondialdehyde and glutathione levels in diabetic and non-diabetic erectile dysfunction. Int J Androl. 2003 Aug; 26 (4): 250–4.
- Hirata H, Kawamoto K, Kikuno N, Kawakami T, Kawakami K, Saini S, et al. Restoring Erectile Function by Antioxidant Therapy in Diabetic Rats. J Urol. 2009 Nov;182 (5): 2518–25.
- Shukla N, Rossoni G, Hotston M, Sparatore A, Del Soldato P, Tazzari V, et al. Effect of hydrogen sulphide-donating sildenafil (ACS6) on erectile function and oxidative stress in rabbit isolated corpus cavernosum and in hypertensive rats. BJU Int. 2009 Jun; 103 (11): 1522–9. 31. Bai, Y., & An, R. Resveratrol and sildenafil synergistically improve diabetes-associated erectile dysfunction in streptozotocin-induced diabetic rats. Life sciences, 2015, 135: 43-48.
- Han J, Kim N, Joo H, Kim E, Earm YE. ATP-sensitive K+ channel activation by nitric oxide and protein kinase G in rabbit ventricular myocytes. Am J Physiol - Hear Circ Physiol. 2002 Oct; 283 (4 52-4).
- Zusman, R. M., et al. Overall cardiovascular profile of sildenafil citrate. The American journal of cardiology, 1999, 83.5: 35-44.
- Vignozzi L, Filippi S, Morelli A, Ambrosini S, Luconi M, Vannelli GB, et al. Effect of chronic tadalafil administration on penile hypoxia induced by cavernous neurotomy in the rat. J Sex Med. 2006; 3 (3): 419–31.
- Lucas, K. A., et al. Guanylyl cyclases and signaling by cyclic GMP. Pharmacological reviews, 2000, 52.3: 375-414.
- Medina, P., et al. Effects of sildenafil on human penile blood vessels. Urology, 2000, 56.3: 539-543.
- Ferrini, M. G., et al. Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat. Urology, 2006, 68.2: 429-435.
- Ferrini, M. G., et al. Long-term continuous treatment with sildenafil ameliorates aging-related erectile dysfunction and the underlying corporal fibrosis in the rat. Biology of reproduction, 2007, 76.5: 915-923.
- Xu Y, Xin H, Wu Y, Guan R, Lei H, Fu X, et al. Effect of icariin in combination with daily sildenafil on penile atrophy and erectile dysfunction in a rat model of bilateral cavernous nerves injury. Andrology. 2017 May 1; 5 (3): 598–605.
- Özden E, Öztürk B, Koşan M, et al. Effect of sildenafil citrate on penile weight and physiology of cavernous smooth muscle in a post-radical prostatectomy model of erectile dysfunction in rats. Urology. 2011; 77 (3): 761.e1–761.e7617.
- De Young LX, Domes T, Lim K Bin, Carson J, Brock GB. Endothelial Rehabilitation: The Impact of Chronic PDE5 Inhibitors on Erectile Function and Protein Alterations in Cavernous Tissue of Diabetic Rats. Eur Urol. 2008 Jul 1; 54 (1): 213–20.
- Bivalacqua TJ, Champion HC, Usta MF, Cellek S, Chitaley K, Webb RC, et al. RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: A mechanism for diabetes-associated erectile dysfunction. Proc Natl Acad Sci U S A. 2004 Jun 15; 101 (24): 9121–6.
- Behr-Roussel, D., et al. Chronic sildenafil improves erectile function and endothelium-dependent cavernosal relaxations in rats: lack of tachyphylaxis. European urology, 2005, 47.1: 87-91.
- Chen, G., et al. Pancreatic kininogenase improves erectile function in streptozotocin-induced type 2 diabetic rats with erectile dysfunction. Asian journal of andrology, 2018, 20.5: 448.
- De Souza DB, Silva D, Cortez CM, Costa WS, Sampaio FJB. Effects of Chronic Stress on Penile Corpus Cavernosum of Rats. J Androl. 2012 Jul 1; 33 (4): 735–9.
- Pinheiro ACAD, Costa WS, Cardoso LEM, Sampaio FJB. Organization and relative content of smooth muscle cells, collagen and elastic fibers in the corpus cavernosum of rat penis. J Urol. 2000; 164: 1802–6.
Öz
Aim: Thyrotoxicosis is a term that meets all clinical pictures caused by excessive thyroid hormone in peripheral blood and tissues. The thyrotoxicosis table negatively affects many organs and metabolic processes. One of them is the male reproductive system. In this experimental study, the histopathological evaluation of the effect of preventing dysfunction of sildenafil treatment in erectile dysfunction due to thyrotoxicosis is aimed.
Materials and Methods: Four study groups were formed, each consisting of 8 rats. These experimental groups: The control group, Thyrotoxicosis (Experimental) group, Thyrotoxicosis+ sildenafil applied group (Treatment group) and Thyrotoxicosis+ sildenafil solvent applied group (Placebo). Male rats in the thyrotoxicosis group were injected with a dose of 0.2 mg / kg / day for 7 days with L-thyroxine. Following the application of L-thyroxine to the treatment group, sildenafil at a dose of 10 mg/kg/day was administered intraperitoneally for 24 days. When the experimental model was completed, 4% paraformaldehyde was taken for histochemical and immunohistochemical examinations. Routine immunohistochemical monitoring and staining were done, and all samples were evaluated under a light microscope.
Results: In the subjects belonging to the experimental group, degeneration in the cavernous spaces, narrowing and loss of endothelial cells were determined. In the rats exposed to thyrotoxicosis in terms of fibroelastic connective tissue and smooth muscle distribution, there was a significant decrease in elastic fibers and smooth muscles and an increase in collagen fibers. In the treatment group, tunica albuginea, corpus cavernosum, venous sinuses, cavernosal trabecular smooth muscle and thin fibrous connective tissue were found to be close to normal histological structure. Diameters of cavernous bodies were found statistically significant (p <0.001). Similar differences were observed in fibrosis, degeneration, and contraction results in cavernous structures. According to the bilateral analysis, while the differences between the control-treatment and experimental-placebo groups were not statistically significant, all other binary differences were found significant (p <0.05). In terms of peripheral nerve degeneration, only the control group's differences with the experimental and placebo groups were found to be significant (p <0.05).
Conclusion: It has been determined that the experimental model of thyrotoxicosis caused histological damage in penile cavernosae. It has been provided that exogenous sildenafil application reduces histopathological degenerative effects.
Anahtar Kelimeler
Kaynakça
- Moon JH, Yi KH. The Diagnosis and Management of Hyperthyroidism in Korea: Consensus Report of the Korean Thyroid Association. Endocrinol Metab. 2013; 28 (4): 275.
- Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct 1; 26 (10): 1343–421.
- Bahn RS, Burch HB, Cooper DS, Garber JR, Carol Greenlee M, Klein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: Management guidelines of the american thyroid association and American association of clinical endocrinoloigists. Endocr Pract. 2011 May 1; 17 (3): 456–520.
- Carani C, Isidori AM, Granata A, Carosa E, Maggi M, Lenzi A, et al. Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients. J Clin Endocrinol Metab. 2005 Dec; 90 (12): 6472–9.
- Krassas GE, Poppe K, Glinoer D. Thyroid Function and Human Reproductive Health. Endocr Rev. 2010 Oct 1; 31 (5): 702–55.
- Patel N, Kashanian J. Thyroid Dysfunction and Male Reproductive Physiology. Semin Reprod Med. 2016 Oct 14;34(06):356–60.
- Gong B, Ma M, Xie W, Yang X, Huang Y, Sun T, et al. Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis. Int Urol Nephrol. 2017 Oct 1; 49 (10): 1731–40.
- Scaglione F, Donde S, Hassan TA, Jannini EA. Phosphodiesterase Type 5 Inhibitors for the Treatment of Erectile Dysfunction: Pharmacology and Clinical Impact of the Sildenafil Citrate Orodispersible Tablet Formulation. Clin Ther. 2017 Feb 1; 39 (2): 370–7.
- Makay O, Yenisey C, Icoz G, Genc Simsek N, Ozgen G, Akyildiz M, Yetkin E. The role of allopurinol on oxidative stress in experimental hyperthyroidism. J Endocrinol Invest. 2009 Sep; 32 (8): 641-6.
- Çekmen, M. B., Turgut, M., Türköz, Y., Aygün, A. D., & Gözükara, E. M. Nitrik Oksit (NO) ve Nitrik Oksit Sentaz (NOS)'ın Fizyolojik ve Patolojik Özellikleri. Turkiye Klinikleri Journal of Pediatrics, 2001; 10 (4), 226-235.
- Thomas, D., et al. The chemical biology of nitric oxide: implications in cellular signaling. Free Radical Biology and Medicine, 2008, 45.1: 18-31.
- Bianchi G, Solaroli E, Zaccheroni V, Grossi G, Bargossi AM, Melchionda N, et al. Oxidative stress and anti-oxidant metabolites in patients with hyperthyroidism: Effect of treatment. Horm Metab Res. 1999; 31 (11): 620–4.
- Venditti, P., et al. Effect of thyroid state on lipid peroxidation, antioxidant defences, and susceptibility to oxidative stress in rat tissues. Journal of Endocrinology, 1997, 155: 151-157.
- Makay, B., et al. The interaction of oxidative stress response with cytokines in the thyrotoxic rat: is there a link?. Mediators of inflammation, 2009, 2009.
- Goldstein, A. M. B., et al. New observations on microarchitecture of corpora cavernosa in man and possible relationship to mechanism of erection. Urology, 1982, 20.3: 259-266.
- Costa WS, Carrerete FB, Horta WG, Sampaio FJB. Comparative analysis of the penis corpora cavernosa in controls and patients with erectile dysfunction. BJU Int. 2006 Mar; 97 (3): 567–9.
- Burnett, A. L., et al. Nitric oxide: a physiologic mediator of penile erection. Science, 1992, 257.5068: 401-403.
- Bassenge E. Coronary vasomotor responses: Role of endothelium and nitrovasodilators. Cardiovasc Drugs Ther. 1994 Aug; 8 (4): 601–10.
- Andersson KE, Wagner G. Physiology of penile erection. Physiol Rev. 1995; 75 (1): 191.
- Gur S, Kadowitz PJ, Gurkan L, Chandra S, Dewitt SY, Harbin A, et al. Chronic inhibition of nitric-oxide synthase induces hypertension and erectile dysfunction in the rat that is not reversed by sildenafil. BJU Int. 2010 Jul; 106 (1): 78–83.
- Ferraz, M., et al. The effects of sildenafil after chronic L-NAME administration in male rat sexual behavior. Pharmacology Biochemistry and Behavior, 2016, 146: 13-20.
- Cashen DE, MacIntyre DE, Martin WJ. Effects of sildenafil on erectile activity in mice lacking neuronal or endothelial nitric oxide synthase. Br J Pharmacol. 2002; 136 (5): 693–700.
- Salonia A, Castagna G, Saccà A, Ferrari M, Capitanio U, Castiglione F, et al. Is Erectile Dysfunction a Reliable Proxy of General Male Health Status? The Case for the International Index of Erectile Function-Erectile Function Domain. J Sex Med. 2012; 9 (10): 2708–15.
- Rajfer J, Aronson WJ, Dorey FJ, Bush PA, Ignarro LJ. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med. 1992 Jan 9; 326 (2): 90–4. 25. Försterrmann, U., et al. Isoforms of nitric oxide synthase: functions in the cardiovascular system.
- European heart journal, 1993, 14: 10-15. 26. Ahn, G. J., et al. Increased expression of the nitric oxide synthase gene and protein in corpus cavernosum by repeated dosing of udenafil in a rat model of chemical diabetogenesis. Asian journal of andrology, 2009, 11.4: 435.
- Angulo J, González-Corrochano R, Cuevas P, Fernández A, Fuente JML, Rolo F, et al. Diabetes exacerbates the functional deficiency of NO/cGMP pathway associated with erectile dysfunction in human corpus cavernosum and penile arteries. J Sex Med. 2010; 7: 758–68.
- Tuncayengin A, Biri H, Onaran M, Şen I, Tuncayengin Ö, Polat F, et al. Cavernosal tissue nitrite, nitrate, malondialdehyde and glutathione levels in diabetic and non-diabetic erectile dysfunction. Int J Androl. 2003 Aug; 26 (4): 250–4.
- Hirata H, Kawamoto K, Kikuno N, Kawakami T, Kawakami K, Saini S, et al. Restoring Erectile Function by Antioxidant Therapy in Diabetic Rats. J Urol. 2009 Nov;182 (5): 2518–25.
- Shukla N, Rossoni G, Hotston M, Sparatore A, Del Soldato P, Tazzari V, et al. Effect of hydrogen sulphide-donating sildenafil (ACS6) on erectile function and oxidative stress in rabbit isolated corpus cavernosum and in hypertensive rats. BJU Int. 2009 Jun; 103 (11): 1522–9. 31. Bai, Y., & An, R. Resveratrol and sildenafil synergistically improve diabetes-associated erectile dysfunction in streptozotocin-induced diabetic rats. Life sciences, 2015, 135: 43-48.
- Han J, Kim N, Joo H, Kim E, Earm YE. ATP-sensitive K+ channel activation by nitric oxide and protein kinase G in rabbit ventricular myocytes. Am J Physiol - Hear Circ Physiol. 2002 Oct; 283 (4 52-4).
- Zusman, R. M., et al. Overall cardiovascular profile of sildenafil citrate. The American journal of cardiology, 1999, 83.5: 35-44.
- Vignozzi L, Filippi S, Morelli A, Ambrosini S, Luconi M, Vannelli GB, et al. Effect of chronic tadalafil administration on penile hypoxia induced by cavernous neurotomy in the rat. J Sex Med. 2006; 3 (3): 419–31.
- Lucas, K. A., et al. Guanylyl cyclases and signaling by cyclic GMP. Pharmacological reviews, 2000, 52.3: 375-414.
- Medina, P., et al. Effects of sildenafil on human penile blood vessels. Urology, 2000, 56.3: 539-543.
- Ferrini, M. G., et al. Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat. Urology, 2006, 68.2: 429-435.
- Ferrini, M. G., et al. Long-term continuous treatment with sildenafil ameliorates aging-related erectile dysfunction and the underlying corporal fibrosis in the rat. Biology of reproduction, 2007, 76.5: 915-923.
- Xu Y, Xin H, Wu Y, Guan R, Lei H, Fu X, et al. Effect of icariin in combination with daily sildenafil on penile atrophy and erectile dysfunction in a rat model of bilateral cavernous nerves injury. Andrology. 2017 May 1; 5 (3): 598–605.
- Özden E, Öztürk B, Koşan M, et al. Effect of sildenafil citrate on penile weight and physiology of cavernous smooth muscle in a post-radical prostatectomy model of erectile dysfunction in rats. Urology. 2011; 77 (3): 761.e1–761.e7617.
- De Young LX, Domes T, Lim K Bin, Carson J, Brock GB. Endothelial Rehabilitation: The Impact of Chronic PDE5 Inhibitors on Erectile Function and Protein Alterations in Cavernous Tissue of Diabetic Rats. Eur Urol. 2008 Jul 1; 54 (1): 213–20.
- Bivalacqua TJ, Champion HC, Usta MF, Cellek S, Chitaley K, Webb RC, et al. RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: A mechanism for diabetes-associated erectile dysfunction. Proc Natl Acad Sci U S A. 2004 Jun 15; 101 (24): 9121–6.
- Behr-Roussel, D., et al. Chronic sildenafil improves erectile function and endothelium-dependent cavernosal relaxations in rats: lack of tachyphylaxis. European urology, 2005, 47.1: 87-91.
- Chen, G., et al. Pancreatic kininogenase improves erectile function in streptozotocin-induced type 2 diabetic rats with erectile dysfunction. Asian journal of andrology, 2018, 20.5: 448.
- De Souza DB, Silva D, Cortez CM, Costa WS, Sampaio FJB. Effects of Chronic Stress on Penile Corpus Cavernosum of Rats. J Androl. 2012 Jul 1; 33 (4): 735–9.
- Pinheiro ACAD, Costa WS, Cardoso LEM, Sampaio FJB. Organization and relative content of smooth muscle cells, collagen and elastic fibers in the corpus cavernosum of rat penis. J Urol. 2000; 164: 1802–6.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Eylül 2020 |
| Gönderilme Tarihi | 8 Mayıs 2020 |
| Yayımlandığı Sayı | Yıl 2020 |