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<p>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 (<i>p</i> &lt; 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年6月6日

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  • Mahla Masoumi,
  • Saba Ahmadi,
  • Razieh Mohammad Jafari,
  • Mohammad Amin Manavi,
  • Seyed Mohammad Tavangar,
  • Ahmad Reza Dehpour

摘要

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.