Hydroxytyrosol promotes random skin flap survival by activating SIRT1-mediated enhancement of autophagy

Abstract

Surgical tissue reconstruction often uses random skin flaps, but ischemic necrosis at the distal end remains a problem. Hydroxytyrosol, a phenolic compound from olive oil, has anti-inflammatory and antioxidative properties. This study investigated whether hydroxytyrosol could promote flap survival and its underlying mechanisms using a mouse model with random skin flaps. Flap necrosis was assessed seven days after surgery, with angiogenesis, apoptosis, oxidative stress, and autophagy evaluated in flap specimens. Compared to controls, the hydroxytyrosol-treated group showed reduced necrotic areas and edema. Immunohistochemistry and Western blotting revealed decreased oxidative stress and apoptosis, with increased angiogenesis. Laser Doppler imaging confirmed enhanced angiogenesis with hydroxytyrosol treatment. The reversal of hydroxytyrosol’s effects by 3-methyladenine underscores autophagy’s role, mediated by SIRT1 activation. Our research indicates that hydroxytyrosol enhances random skin flap survival by activating SIRT1-mediated autophagy.

Keywords

• Autophagy
• Oxidative stress
• Apoptosis
• Hydroxytyrosol
• Random flap