Protective effects of licofelone on experimental skin flap survival rat model via cyclooxygenase and lipoxygenase inhibition: involvement of inflammatory cytokines and nitric oxide.

Ischemia-reperfusion injury remains a critical challenge in reconstructive surgery, often leading to extensive tissue necrosis and compromised skin flap survival. This study investigated the protective effects of licofelone, a dual cyclooxygenase and lipoxygenase inhibitor, in a rat model of random-pattern skin flap ischemia. Forty male Wistar rats underwent skin flap surgery following ischemia induction and were administered licofelone at doses of 1, 5, 10, or 20 mg/kg, with treatment given 30 min before surgery. The extent of flap necrosis was quantified 7 days postoperatively, while inflammatory markers, nitric oxide levels, and the expression of cyclooxygenase-2 and lipoxygenase-5 were assessed through enzyme-linked immunosorbent assay and western blotting. Histological evaluations were performed using hematoxylin and eosin and Masson's trichrome staining. Licofelone at 10 mg/kg significantly reduced necrosis, with a median necrotic area of 18.15% compared to 44% in the control group (p < 0.001). Treatment also markedly decreased interleukin-6, tumor necrosis factor-α, and interleukin-1β levels, as well as nitric oxide accumulation in skin tissue. Western blot analysis confirmed a significant reduction in cyclooxygenase-2 and lipoxygenase-5 expression. Histopathological analysis demonstrated reduced inflammation, epithelial degeneration, edema, and fibrosis in licofelone-treated groups. These findings highlight licofelone as a promising therapeutic agent for improving skin flap viability by modulating inflammatory and nitrergic pathways, suggesting its potential as a preoperative intervention to enhance reconstructive surgery outcomes.