Rosmarinus Improved Skin Flap Survival Through mTOR Dependent Pathway

Introduction: Skin flap application in the clinical practice is restricted due to the ischemic damage and flap necrosis. Rosmarinus oil has been shown to improve a skin flap survival. In the present work we studied the role of mammalian target of rapamycin (mTOR) signaling on rosmarinus-induced flap protection. Methods: A flap surgery was performed on Sprauge-Dawley rats (8 cm in by 3 cm). A week before and a week after the surgery the flaps were treated with topical rosmarinus oil (twice per day). Rapamycin (m-TOR inhibitor) was administered 30 minutes before the flap surgery in rosmarinus-treated or not treated groups. A week after the surgery the malondialdehyde (MDA) contents, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, expression of Bax, Bcl-2, mTOR and p-mTOR were measured in the flap tissue. Results: Topical application of the rosmarinus increased the flap survival (p<0.05), anti-oxidative enzyme activity (SOD, p<0.05) and anti-apoptotic protein Bcl-2 expression. Rosmarinus treatment decreased the flap MDA content, MPO activity, and pro-apoptotic protein Bax expression (p<0.05). Rosmarinus topical application did not change mTOR expression and phosphorylation in the flap tissue. Expression of p-mTOR in rosmarinus treated group was suppressed by rapamycin pre-treatment, which also abolished rosmarinus effects on the flap survival (p<0.05). Conclusion: These data suggested p-mTOR dependent mechanism in rosmarinus-induced flap survival.