FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms

Gwen Lagoda, Liming Jin, Todd J. Lehrfeld, Tongyun Liu, Arthur Burnett

Research output: Contribution to journalArticle

Abstract

Introduction. Immunophilin ligands and phosphodiesterase type 5 (PDE5) inhibitors are touted to promote erectile function recovery after cavernous nerve (CN) injury. However, the mechanisms for their effects remain unclear. Aim. To compare the erection recovery effects of the immunophilin ligand FK506 and the PDE5 inhibitor sildenafil after CN injury and determine whether they involve antioxidative and/or antiapoptotic mechanisms. Methods. Initial experiments established conditions of our CN injury model in adult male Sprague-Dawley rats. Subsequently, we evaluated treatment effects 14 days after: (i) unilateral CN injury (UNI) + saline (vehicle control); (ii) UNI + FK506 (5mg/kg once daily, subcutaneous ×5 days); (iii) UNI + sildenafil (20 mg/kg every 8 hours, subcutaneous ×7 days); (iv) UNI + FK506/sildenafil; and (v) sham surgery. Main Outcome Measures. Intracavernous pressure (ICP) measurement after CN electrical stimulation to assess erectile function and Western blot analysis of expressions of glutathione peroxidase (GPX; antioxidant enzyme), nitrotyrosine (NT; oxidative stress marker), and phosphorylated and total Akt (antiapoptotic factor) in penes. Results. In the UNI model, GPX expression was increased at Days 1 and 7, while p-Akt expression decreased at Day 1 and returned to baseline at Day 7. GPX expression was significantly higher in the UNI + FK506 group compared with the saline-treated group (P

Original languageEnglish (US)
Pages (from-to)908-916
Number of pages9
JournalJournal of Sexual Medicine
Volume4
Issue number4 I
DOIs
StatePublished - Jul 2007

Fingerprint

Recovery of Function
Tacrolimus
Wounds and Injuries
Immunophilins
Phosphodiesterase 5 Inhibitors
Ligands
Sildenafil Citrate
Glutathione Peroxidase
Electric Stimulation
Sprague Dawley Rats
Oxidative Stress
Antioxidants
Western Blotting
Outcome Assessment (Health Care)
Pressure
Enzymes

Keywords

  • Antiapoptotic
  • Antioxidant enzyme
  • Cavernous nerve
  • FK506
  • Oxidative stress

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynecology

Cite this

FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. / Lagoda, Gwen; Jin, Liming; Lehrfeld, Todd J.; Liu, Tongyun; Burnett, Arthur.

In: Journal of Sexual Medicine, Vol. 4, No. 4 I, 07.2007, p. 908-916.

Research output: Contribution to journalArticle

Lagoda, Gwen ; Jin, Liming ; Lehrfeld, Todd J. ; Liu, Tongyun ; Burnett, Arthur. / FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. In: Journal of Sexual Medicine. 2007 ; Vol. 4, No. 4 I. pp. 908-916.
@article{a241c220949f43018986684271104cf4,
title = "FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms",
abstract = "Introduction. Immunophilin ligands and phosphodiesterase type 5 (PDE5) inhibitors are touted to promote erectile function recovery after cavernous nerve (CN) injury. However, the mechanisms for their effects remain unclear. Aim. To compare the erection recovery effects of the immunophilin ligand FK506 and the PDE5 inhibitor sildenafil after CN injury and determine whether they involve antioxidative and/or antiapoptotic mechanisms. Methods. Initial experiments established conditions of our CN injury model in adult male Sprague-Dawley rats. Subsequently, we evaluated treatment effects 14 days after: (i) unilateral CN injury (UNI) + saline (vehicle control); (ii) UNI + FK506 (5mg/kg once daily, subcutaneous ×5 days); (iii) UNI + sildenafil (20 mg/kg every 8 hours, subcutaneous ×7 days); (iv) UNI + FK506/sildenafil; and (v) sham surgery. Main Outcome Measures. Intracavernous pressure (ICP) measurement after CN electrical stimulation to assess erectile function and Western blot analysis of expressions of glutathione peroxidase (GPX; antioxidant enzyme), nitrotyrosine (NT; oxidative stress marker), and phosphorylated and total Akt (antiapoptotic factor) in penes. Results. In the UNI model, GPX expression was increased at Days 1 and 7, while p-Akt expression decreased at Day 1 and returned to baseline at Day 7. GPX expression was significantly higher in the UNI + FK506 group compared with the saline-treated group (P",
keywords = "Antiapoptotic, Antioxidant enzyme, Cavernous nerve, FK506, Oxidative stress",
author = "Gwen Lagoda and Liming Jin and Lehrfeld, {Todd J.} and Tongyun Liu and Arthur Burnett",
year = "2007",
month = "7",
doi = "10.1111/j.1743-6109.2007.00519.x",
language = "English (US)",
volume = "4",
pages = "908--916",
journal = "Journal of Sexual Medicine",
issn = "1743-6095",
publisher = "Wiley-Blackwell",
number = "4 I",

}

TY - JOUR

T1 - FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms

AU - Lagoda, Gwen

AU - Jin, Liming

AU - Lehrfeld, Todd J.

AU - Liu, Tongyun

AU - Burnett, Arthur

PY - 2007/7

Y1 - 2007/7

N2 - Introduction. Immunophilin ligands and phosphodiesterase type 5 (PDE5) inhibitors are touted to promote erectile function recovery after cavernous nerve (CN) injury. However, the mechanisms for their effects remain unclear. Aim. To compare the erection recovery effects of the immunophilin ligand FK506 and the PDE5 inhibitor sildenafil after CN injury and determine whether they involve antioxidative and/or antiapoptotic mechanisms. Methods. Initial experiments established conditions of our CN injury model in adult male Sprague-Dawley rats. Subsequently, we evaluated treatment effects 14 days after: (i) unilateral CN injury (UNI) + saline (vehicle control); (ii) UNI + FK506 (5mg/kg once daily, subcutaneous ×5 days); (iii) UNI + sildenafil (20 mg/kg every 8 hours, subcutaneous ×7 days); (iv) UNI + FK506/sildenafil; and (v) sham surgery. Main Outcome Measures. Intracavernous pressure (ICP) measurement after CN electrical stimulation to assess erectile function and Western blot analysis of expressions of glutathione peroxidase (GPX; antioxidant enzyme), nitrotyrosine (NT; oxidative stress marker), and phosphorylated and total Akt (antiapoptotic factor) in penes. Results. In the UNI model, GPX expression was increased at Days 1 and 7, while p-Akt expression decreased at Day 1 and returned to baseline at Day 7. GPX expression was significantly higher in the UNI + FK506 group compared with the saline-treated group (P

AB - Introduction. Immunophilin ligands and phosphodiesterase type 5 (PDE5) inhibitors are touted to promote erectile function recovery after cavernous nerve (CN) injury. However, the mechanisms for their effects remain unclear. Aim. To compare the erection recovery effects of the immunophilin ligand FK506 and the PDE5 inhibitor sildenafil after CN injury and determine whether they involve antioxidative and/or antiapoptotic mechanisms. Methods. Initial experiments established conditions of our CN injury model in adult male Sprague-Dawley rats. Subsequently, we evaluated treatment effects 14 days after: (i) unilateral CN injury (UNI) + saline (vehicle control); (ii) UNI + FK506 (5mg/kg once daily, subcutaneous ×5 days); (iii) UNI + sildenafil (20 mg/kg every 8 hours, subcutaneous ×7 days); (iv) UNI + FK506/sildenafil; and (v) sham surgery. Main Outcome Measures. Intracavernous pressure (ICP) measurement after CN electrical stimulation to assess erectile function and Western blot analysis of expressions of glutathione peroxidase (GPX; antioxidant enzyme), nitrotyrosine (NT; oxidative stress marker), and phosphorylated and total Akt (antiapoptotic factor) in penes. Results. In the UNI model, GPX expression was increased at Days 1 and 7, while p-Akt expression decreased at Day 1 and returned to baseline at Day 7. GPX expression was significantly higher in the UNI + FK506 group compared with the saline-treated group (P

KW - Antiapoptotic

KW - Antioxidant enzyme

KW - Cavernous nerve

KW - FK506

KW - Oxidative stress

UR - http://www.scopus.com/inward/record.url?scp=34447498964&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447498964&partnerID=8YFLogxK

U2 - 10.1111/j.1743-6109.2007.00519.x

DO - 10.1111/j.1743-6109.2007.00519.x

M3 - Article

C2 - 17627738

AN - SCOPUS:34447498964

VL - 4

SP - 908

EP - 916

JO - Journal of Sexual Medicine

JF - Journal of Sexual Medicine

SN - 1743-6095

IS - 4 I

ER -