Improvement of tissue survival of skin flaps by 5α-reductase inhibitors: possible involvement of nitric oxide and inducible nitric oxide synthase

Iran Biomed J. 2015;19(2):111-6. doi: 10.6091/ibj.1408.2015.


Background: Skin flap grafting is a popular approach for reconstruction of critical skin and underlying soft tissue injuries. In a previous study, we demonstrated the beneficial effects of two 5α-reductase inhibitors, azelaic acid and finasteride, on tissue survival in a rat model of skin flap grafting. In the current study, we investigated the involvement of nitric oxide and inducible nitric oxide synthase (iNOS) in graft survival mediated by these agents.

Methods: A number of 42 male rats were randomly allocated into six groups: 1, normal saline topical application; 2, azelaic acid (100 mg/flap); 3, finasteride (1 mg/flap); 4, injection of L-NG-nitroarginine methyl ester (L-NAME) (i.p., 20 mg/kg); 5, L-NAME (20 mg/kg, i.p.) + azelaic acid (100 mg/flap, topical); 6, L-NAME (20 mg/kg, i.p.) + finasteride (1 mg/flap, topical). Tissue survival, level of nitric oxide, and iNOS expression in groups were measured.

Results: Our data revealed that azelaic acid and finasteride significantly increased the expression of iNOS protein and nitric oxide (NO) levels in graft tissue (P < 0.05). These increases in iNOS expression and NO level were associated with higher survival of the graft tissue.

Conclusion: It appears that alterations of the NO metabolism are implicated in the azelaic acid- and finasteride-mediated survival of the skin flaps.

Keywords: Finasteride; Azelaic acid; Surgical flaps; Nitric oxide synthase Type II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-alpha Reductase Inhibitors / pharmacology*
  • Animals
  • Cholestenone 5 alpha-Reductase / metabolism
  • Dicarboxylic Acids / pharmacology
  • Finasteride / pharmacology
  • Graft Survival / drug effects
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type II / metabolism*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reconstructive Surgical Procedures / methods*
  • Skin / metabolism
  • Skin Transplantation / methods
  • Soft Tissue Injuries / surgery
  • Surgical Flaps / surgery*
  • Tissue Survival / drug effects


  • 5-alpha Reductase Inhibitors
  • Dicarboxylic Acids
  • Nitric Oxide
  • Finasteride
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Cholestenone 5 alpha-Reductase
  • azelaic acid
  • NG-Nitroarginine Methyl Ester