Objective: Erectile dysfunction is commonly encountered after radical prostatectomy due to cavernous nerve injury (CNI). We investigated the effects of riboflavin (Rb) on bilateral CNI in a rat model. Materials and Methods: Twenty-four male rats were divided into four groups: control (C), patients with bilateral CNI, those with CNI receiving postoperative Rb treatment (CNI+Rb), and those with CNI receiving pre- and post-operative Rb treatment (Rb+CNI+Rb). Bilateral CNI was performed in all groups except for C. The CNI+Rb group was treated with 30 mg/kg Rb daily after CNI for two weeks; the Rb+CNI+Rb group was treated with 30 mg/kg Rb daily one week before CNI and then for two weeks after injury. Mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured 14 days after CNI in all groups. Tissue malondialdehyde, cyclic guanosine monophosphate, nerve growth factor, superoxide dismutase and total nitric oxide synthase (NOS) activities, neuronal NOS (nNOS) and inducible NOS (iNOS) were analyzed. Results: ICP/MAP ratio was significantly lower in the CNI (p
Amaç: Çalışmamızın amacı radikal prostatektomi modelinde erektil disfonksiyon tedavisinde riboflavinin (Rb) olası etkilerinin araştırılmasıdır. Gereç ve Yöntem: Yirmi dört erkek sıçan kontrol (K), bilateral kavernoz sinir hasarı (KSH), KSH+Rb ve Rb +KSH+ Rb olmak üzere 4 gruba ayrıldı. Ön-tedavili KSH grubunda cerrahiden 1 hafta önce başlayarak toplam 3 hafta ve KSH+Rb grubuna ise cerrahiden sonra 2 hafta süreyle 30 mg/kg dozunda Rb uygulandı. Deney sonunda intrakavernosal basınç (İKB) ve ortalama arteryel basınç (OAB) ölçümü yapıldı. Kavernoz doku örneklerinde malondialdehit (MDA), siklik guanozin monofosfat (c-GMP) ve sinir büyüme faktörü (NGF) düzeyleri ile süperoksid dismutaz (SOD) ve total nitrik oksit sentaz (NOS) aktiviteleri ölçüldü. Dokuların indüklenebilir NOS ve nöronal NOS protein ekspresyonları Western blot yöntemi ile tayin edildi. Bulgular: KSH, İKB/OAB değerlerinde anlamlı azalmaya (p
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:359386.
Cai LY, Kato T, Ito K, Nakayama M, Susa T, Aikawa S, Maeda K, Tsukamura H, Ohta A, Izumi S, Kato Y. Expression of porcine FSHbeta subunit promoterdriven herpes simplex virus thymidine kinase gene in transgenic rats. J Reprod Dev 2007;53:201-209.
Podlasek CA, Gonzalez CM, Zelner DJ, Jiang HB, McKenna KE, McVary KT. Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction. Int J Impot Res 2001;13(Suppl 5):1-15.
Salonia A, Burnett AL, Graefen M, Hatzimouratidis K, Montorsi F, Mulhall JP, Stief C. Prevention and management of postprostatectomy sexual dysfunctions. Part 1: choosing the right patient at the right time for the right surgery. Eur Urol 2012;62:261-272.
Agarwal A, Nandipati KC, Sharma RK, Zippe CD, Raina R. Role of oxidative stress in the pathophysiological mechanism of erectile dysfunction. J Androl 2006;27:335-347.
. Ferrini MG, Davila HH, Kovanecz I, Sanchez SP, Gonzalez-Cadavid NF, Rajfer J. Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat. Urology 2006;68:429-435.
Lagoda G, Jin L, Lehrfeld TJ, Liu T, Burnett AL. FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. J Sex Med 2007;4:908-916.
User HM, Hairston JH, Zelner DJ, McKenna KE, McVary KT. Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction. J Urol 2003;169:1175-1179.
Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996;271:1424-1437.
Walsh PC. The discovery of the cavernous nerves and development of nerve sparing radical retropubic prostatectomy. J Urol 2007;177:1632-1635.
Burnett AL. Strategies to promote recovery of cavernous nerve function after radical prostatectomy. World J Urol 2003;20:337-342.
Miyamoto K, Inoue S, Kobayashi K, Kajiwara M, Teishima J, Matsubara A. Rat cavernous nerve reconstruction with CD133+ cells derived from human bone marrow. J Sex Med 2014;11:1148-1158.
Sezen SF, Hoke A, Burnett AL, Snyder SH. Immunophilin ligand FK506 is neuroprotective for penile innervation. Nat Med 2001;7:1073-1074.
Burnett AL, Allaf ME, Bivalacqua TJ. Erythropoietin promotes erection recovery after nerve-sparing radical retropubic prostatectomy: a retrospective analysis. J Sex Med 2008;5:2392-2398.
Jung GW, Kwak JY, Yoon S, Yoon JH, Lue TF. IGF-I and TGF-beta2 have a key role on regeneration of nitric oxide synthase (NOS)-containing nerves after cavernous neurotomy in rats. Int J Impot Res 1999;11:247-259.
Sezen SF, Blackshaw S, Steiner JP, Burnett AL. FK506 binding protein 12 is expressed in rat penile innervation and upregulated after cavernous nerve injury. Int J Impot Res 2002;14:506-512.
Kato R, Wolfe D, Coyle CH, Huang S, Wechuck JB, Goins WF, Krisky DM, Tsukamoto T, Nelson JB, Glorioso JC, Chancellor MB, Yoshimura N. Herpes simplex virus vector-mediated delivery of glial cell line-derived neurotrophic factor rescues erectile dysfunction following cavernous nerve injury. Gene Ther 2007;14:1344-1352.
Kim Y, de Miguel F, Usiene I, Kwon D, Yoshimura N, Huard J, Chancellor MB. Injection of skeletal muscle-derived cells into the penis improves erectile function. Int J Impot Res 2006;18:329-334.
Bochinski D, Lin GT, Nunes L, Carrion R, Rahman N, Lin CS, Lue TF. The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury. BJU Int 2004;94:904-909.
Lin G, Qiu X, Fandel T, Banie L, Wang G, Lue TF, Lin CS. Tracking intracavernously injected adipose-derived stem cells to bone marrow. Int J Impot Res 2011;23:268-275.
Chen KC, Minor TX, Rahman NU, Ho HC, Nunes L, Lue TF. The additive erectile recovery effect of brain-derived neurotrophic factor combined with vascular endothelial growth factor in a rat model of neurogenic impotence. BJU Int 2005;95:1077-1080.
Bochinski D, Hsieh PS, Nunes L, Lin GT, Lin CS, Spencer EM, Lue TF. Effect of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 complex in cavernous nerve cryoablation. Int J Impot Res 2004;16:418-423.
Marashly ET, Bohlega SA. Riboflavin has neuroprotective potential: focus on Parkinson’s disease and migraine. Front Neurol 2017;8:333.
Sakarcan S, Erşahin M, Eminoğlu ME, Çevik Ö, Ak E, Ercan F, Şener G. Riboflavin treatment reduces apoptosis and oxidative DNA damage in a rat spinal cord injury model. Clin Exp Healh Sci 2017;7:55-63.
Bertollo CM, Oliveira AC, Rocha LT, Costa KA, Nascimento EB Jr, Coelho MM. Characterization of the antinociceptive and anti-inflammatory activities of riboflavin in different experimental models. Eur J Pharmacol 2006;547:184191.
Mullerad M, Donohue JF, Li PS, Scardino PT, Mulhall JP. Functional sequelae of cavernous nerve injury in the rat: is there model dependency? J Sex Med 2006;3:77-83.
Mylroie AA, Collins H, Umbles C, Kyle J. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol 1986;82:512-520.
Tavukcu HH, Sener TE, Tinay I, Akbal C, Ersahin M, Cevik O, Cadirci S, Reiter RJ, Sener G. Melatonin and tadalafil treatment improves erectile dysfunction after spinal cord injury in rats. Clin Exp Pharmacol Physiol 2014;41:309-316.
. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-254.
Cevik O, Ersahin M, Sener TE, Tinay I, Tarcan T, Cetinel S, Sener A, Toklu HZ, Sener G. Beneficial effects of quercetin on rat urinary bladder after spinal cord injury. J Surg Res 2013;183:695-703.
Mulhall JP, Muller A, Donohue JF, Mullerad M, Kobylarz K, Paduch DA, Tal R, Li PS, Cohen-Gould L, Scardino PT. The functional and structural consequences of cavernous nerve injury are ameliorated by sildenafil citrate. J Sex Med 2008;5:1126-1136.
Hsieh PS, Bochinski DJ, Lin GT, Nunes L, Lin CS, Lue TF. The effect of vascular endothelial growth factor and brain-derived neurotrophic factor on cavernosal nerve regeneration in a nerve-crush rat model. BJU Int 2003;92:470-475.
Fiore M, Chaldakov GN, Aloe L. Nerve growth factor as a signaling molecule for nerve cells and also for the neuroendocrine-immune systems. Rev Neurosci 2009;20:133-145.
Blecher G, Almekaty K, Kalejaiye O, Minhas S. Does penile rehabilitation have a role in the treatment of erectile dysfunction following radical prostatectomy? F1000Res 2017;6:1923.
Tavukcu HH, Akbal C, Tinay I, Simsek F, Türkeri L. Outcome of preemptive penile rehabilitation before bilateral cavernosal nerve injury in rats. World J Urol 2010;28:735-740.