N-acetylcysteine maintains penile length and erectile function in bilateral cavernous nerve crush rat model by reducing penile fibrosis

Asian J Androl. 2021 Mar-Apr;23(2):215-221. doi: 10.4103/aja.aja_17_20.


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.

Keywords: N-acetylcysteine; erectile dysfunction; penile fibrosis; penile length.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Actins / drug effects
  • Actins / metabolism
  • Animals
  • Collagen / drug effects
  • Collagen / metabolism
  • Crush Injuries / metabolism*
  • Crush Injuries / pathology
  • Crush Injuries / physiopathology
  • Disease Models, Animal
  • Erectile Dysfunction / prevention & control
  • Fibrosis
  • Free Radical Scavengers / pharmacology*
  • Glutathione / drug effects
  • Glutathione / metabolism
  • Glutathione Peroxidase / drug effects
  • Glutathione Peroxidase / metabolism
  • Glutathione Peroxidase GPX1
  • Hypoxia-Inducible Factor 1, alpha Subunit / drug effects
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Nitric Oxide Synthase Type III / drug effects
  • Nitric Oxide Synthase Type III / metabolism
  • Organ Size
  • Penile Erection / drug effects*
  • Penis / drug effects*
  • Penis / innervation
  • Penis / pathology
  • Peripheral Nerve Injuries / metabolism*
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / physiopathology
  • Postoperative Complications / prevention & control
  • Prostatectomy
  • Prostatic Neoplasms / surgery
  • Protein-Lysine 6-Oxidase / drug effects
  • Protein-Lysine 6-Oxidase / metabolism
  • Rats
  • Transforming Growth Factor beta1 / drug effects
  • Transforming Growth Factor beta1 / metabolism


  • Actins
  • Free Radical Scavengers
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • smooth muscle actin, rat
  • Malondialdehyde
  • Collagen
  • Glutathione Peroxidase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Protein-Lysine 6-Oxidase
  • Glutathione
  • Acetylcysteine
  • Glutathione Peroxidase GPX1
  • Gpx1 protein, rat