Improvement of Tissue Survival of Skin Flaps by 5α-Reductase Inhibitors: Possible Involvement of Nitric Oxide and Inducible Nitric Oxide Synthase

Authors
Ali Asghar Karimi
Marjan Ajami
Yasin Asadi
Nahid Aboutaleb
Fazel Gorjipour
Roya Malekloo
Hamidreza Pazoki-Toroudi
10.6091/ibj.1408.2015
Abstract
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
Nitric oxide synthase Type II