N-acetylcysteine Maintains Penile Length and Erectile Function in Bilateral Cavernous Nerve Crush Rat Model by Reducing Penile Fibrosis

Overview

Journal Asian J Androl

Specialty Urology

Date 2020 May 13

PMID 32394901

Authors

Ming Ma

Chang-Jing Wu

Peng Zhang

Tao Li

Shan-Zun Wei

Bo-Tao Yu

Feng Qin

Jiu-Hong Yuan

Affiliations

Soon will be listed here.

Abstract

Penile length shortening and erectile dysfunction are common complications after radical prostatectomy. Various methods have been used to maintain erectile function, but less attention has been paid to preserving penis length. N-acetylcysteine (NAC) has the effect of antioxidation and antifibrotic, which may be beneficial to improve those postoperative complications. This study investigated the effect of NAC on maintaining the penile length and the erectile function after bilateral cavernous nerve crush (BCNC) and its underlying mechanism. Twenty-four male rats were randomly divided into three groups: control group, BCNC group, and BCNC + NAC group. NAC or equal volume of saline was daily administrated by intragastric gavage for 4 weeks. The initial and end penile lengths were measured. Intracavernosal pressure/mean arterial pressure (ICP/MAP) ratio was calculated to assess erectile function. Hematoxylin-eosin staining, Masson's trichrome staining, immunohistochemistry, and Western blot were performed to explore cellular and molecular changes of the penis. Compared to the BCNC group, the penile length, ICP/MAP ratio and smooth muscle/collagen ratio in the BCNC + NAC group were improved significantly (all P < 0.05), and the expressions of endothelial nitric oxide synthase, α-smooth muscle actin, glutathione, and glutathione peroxidase 1 were significantly increased after NAC treated (all P < 0.05), along with the decreased expressions of hypoxia-inducible factor-1α, transforming growth factor-β1, collagen I, collagen III, collagen IV, malonaldehyde, and lysine oxidase (all P < 0.05). This study demonstrated that NAC could maintain penile length and partly improve erectile function. Possible mechanism is directly and/or indirectly related to antihypoxic and antifibrosis.

References

Heil J, Schultze D, Schemmer P, Bruns H . N-acetylcysteine protects hepatocytes from hypoxia-related cell injury. Clin Exp Hepatol. 2019; 4(4):260-266. PMC: 6311746. DOI: 10.5114/ceh.2018.80128. View

Jan Y, Lai T, Yang C, Lin Y, Huang M, Hsiao M . Adenylate kinase 4 modulates oxidative stress and stabilizes HIF-1α to drive lung adenocarcinoma metastasis. J Hematol Oncol. 2019; 12(1):12. PMC: 6352453. DOI: 10.1186/s13045-019-0698-5. View

Nave A, Mizikova I, Niess G, Steenbock H, Reichenberger F, Talavera M . Lysyl oxidases play a causal role in vascular remodeling in clinical and experimental pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol. 2014; 34(7):1446-58. DOI: 10.1161/ATVBAHA.114.303534. View

Montorsi F, Oelke M, Henneges C, Brock G, Salonia A, dAnzeo G . Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy. Eur Urol. 2016; 70(3):529-37. PMC: 5478190. DOI: 10.1016/j.eururo.2016.02.036. View

Raina R, Pahlajani G, Agarwal A, Jones S, Zippe C . Long-term potency after early use of a vacuum erection device following radical prostatectomy. BJU Int. 2010; 106(11):1719-22. DOI: 10.1111/j.1464-410X.2010.09360.x. View

Liao W, Xiang W, Wang F, Wang R, Ding Y . Curcumin inhibited growth of human melanoma A375 cells via inciting oxidative stress. Biomed Pharmacother. 2017; 95:1177-1186. DOI: 10.1016/j.biopha.2017.09.026. View

Ozbey H, Temiz A, Salman T . A simple method for measuring penile length in newborns and infants. BJU Int. 1999; 84(9):1093-4. DOI: 10.1046/j.1464-410x.1999.00366.x. View

Kopp J, Seyhan H, Muller B, Lanczak J, Pausch E, Gressner A . N-acetyl-L-cysteine abrogates fibrogenic properties of fibroblasts isolated from Dupuytren's disease by blunting TGF-beta signalling. J Cell Mol Med. 2006; 10(1):157-65. PMC: 3933108. DOI: 10.1111/j.1582-4934.2006.tb00297.x. View

Wolf A, Wender R, Etzioni R, Thompson I, DAmico A, Volk R . American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin. 2010; 60(2):70-98. DOI: 10.3322/caac.20066. View

10.

Montorsi F, McCullough A . Efficacy of sildenafil citrate in men with erectile dysfunction following radical prostatectomy: a systematic review of clinical data. J Sex Med. 2006; 2(5):658-67. DOI: 10.1111/j.1743-6109.2005.00117.x. View

11.

Coombs P, Heck M, Guhring P, Narus J, Mulhall J . A review of outcomes of an intracavernosal injection therapy programme. BJU Int. 2012; 110(11):1787-91. DOI: 10.1111/j.1464-410X.2012.11080.x. View

12.

Gao L, Wu C, Fu F, You X, Ma X, Qin F . Effect of lysyl oxidase (LOX) on corpus cavernous fibrosis caused by ischaemic priapism. J Cell Mol Med. 2017; 22(3):2018-2022. PMC: 5824375. DOI: 10.1111/jcmm.13411. View

13.

Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen H . High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005; 353(21):2229-42. DOI: 10.1056/NEJMoa042976. View

14.

Garcia-Trevijano E, Iraburu M, Fontana L, Dominguez-Rosales J, Auster A, Rojkind M . Transforming growth factor beta1 induces the expression of alpha1(I) procollagen mRNA by a hydrogen peroxide-C/EBPbeta-dependent mechanism in rat hepatic stellate cells. Hepatology. 1999; 29(3):960-70. DOI: 10.1002/hep.510290346. View

15.

Saporito-Magrina C, Musacco-Sebio R, Andrieux G, Kook L, Orrego M, Tuttolomondo M . Copper-induced cell death and the protective role of glutathione: the implication of impaired protein folding rather than oxidative stress. Metallomics. 2018; 10(12):1743-1754. DOI: 10.1039/c8mt00182k. View

16.

OLeary A, Drummond S, Edge D, OHalloran K . Diaphragm Muscle Weakness Following Acute Sustained Hypoxic Stress in the Mouse Is Prevented by Pretreatment with N-Acetyl Cysteine. Oxid Med Cell Longev. 2018; 2018:4805493. PMC: 5836441. DOI: 10.1155/2018/4805493. View

17.

Ahmed K, Hatzimouratidis K, Muneer A . Male Sexual Dysfunction and Hypogonadism Guidelines for the Aging Male. Eur Urol Focus. 2018; 3(4-5):514-516. DOI: 10.1016/j.euf.2017.12.004. View

18.

Kim N, Vardi Y, Padma-Nathan H, Daley J, Goldstein I, Saenz de Tejada I . Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection. J Clin Invest. 1993; 91(2):437-42. PMC: 287949. DOI: 10.1172/JCI116220. View

19.

White A, Maloney E, Lee S, Lanzillo J, Fanburg B . Reduction of endothelial cell related TGFbeta activity by thiols. Endothelium. 1999; 6(3):231-9. DOI: 10.3109/10623329909053413. View

20.

Huang K, Wu C, Huang K, Lin W, Chen C, Guan S . Titanium nanoparticle inhalation induces renal fibrosis in mice via an oxidative stress upregulated transforming growth factor-β pathway. Chem Res Toxicol. 2014; 28(3):354-64. DOI: 10.1021/tx500287f. View