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

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 5alpha-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. 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-N[G]-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. 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. It appears that alterations of the NO metabolism are implicated in the azelaic acid- and finasteride-mediated survival of the skin flaps

BCL-2 and bax expression in skin flaps treated with finasteride or azelaic acid

Despite all modern surgical techniques, skin flap that is considered as the main method in most reconstructive surgeries puts the skin tissue at danger of necrosis and apoptosis derived from ischemia. Therefore, finding a treatment for decreasing the apoptosis derived from flap ischemia will be useful in clinic. In present study, we evaluated the effect of azelaic acid 20% and finasteride on expression of BCL-2 and bax proteins after the skin flap surgery. For this purpose, 21 rats were entered in three groups including control, azelaic acid 20% and finasteride, all experienced skin flap surgery and then flap tissue was assessed for determining the expression of proteins in 5 slices prepared from each rat that were graded between - to +++ scales. Both azelaic acid and finasteride increased the expression of BCL-2 protein [p < 0.05] and decrease the expression of bax protein [p < 0.05]. These results suggested an antiapoptotic role for finasteride and azelaic acid in preserving the flap after the ischemia reperfusion insult