Montelukast protects axial pattern rat skin flaps against ischemia/reperfusion injury

J Surg Res. 2009 Dec;157(2):181-6. doi: 10.1016/j.jss.2008.07.031. Epub 2008 Aug 27.


Background: Recent studies have shown that neutrophils play an important role in the pathogenesis of reperfusion injury. Using an inferior epigastric artery skin flap as a flap ischemia/reperfusion (I/R) injury model, we investigated whether the administration of montelukast sodium, a selective reversible cysteinyl leukotriene 1 (CysLT1) receptor antagonist, decreases neutrophil infiltration and promotes flap survival.

Methods: Eighteen rats were used and randomly divided into three groups (n=6 for each group). Group I was the sham group and did not undergo ischemic insult; rather, normal saline (1 mL) was administrated intraperitonealy (i.p.) 30 min before surgery and continued for 6 d. Group II (control) and Group III (montelukast) underwent 12 h of ischemic insult. For Group II, normal saline (1 mL) was injected i.p. 30 min before the surgery and immediately before reperfusion, and this continued for 6 d. In Group III, 1 mL of montelukast (10mg/kg) was injected i.p. and continued for 6 d. Malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) enzyme activities were investigated. Histological evaluation was made to investigate the tissue neutrophil count. Survival areas were assessed at 7 d postoperatively.

Results: Group III (montelukast- treated) showed a significantly higher survival rate than Group II (control) (P=0.029) but a lower survival rate than Group I (sham). Histological and biochemical assays corroborated this data.

Conclusion: This study suggests that montelukast CysLT1 receptor antagonist montelukast reversed I/R-induced oxidant responses and improved flap survival by inhibiting neutrophil infiltration and balancing oxidant and antioxidant status.

MeSH terms

  • Acetates / administration & dosage
  • Acetates / therapeutic use*
  • Animals
  • Cell Movement / physiology
  • Glutathione / metabolism
  • Graft Survival / physiology*
  • Injections, Intraperitoneal
  • Leukotriene Antagonists / administration & dosage
  • Leukotriene Antagonists / therapeutic use*
  • Male
  • Malondialdehyde / metabolism
  • Models, Animal
  • Neutrophils / pathology
  • Peroxidase / metabolism
  • Quinolines / administration & dosage
  • Quinolines / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Skin Transplantation / pathology
  • Skin Transplantation / physiology*
  • Surgical Flaps / pathology
  • Surgical Flaps / physiology*
  • Treatment Outcome


  • Acetates
  • Leukotriene Antagonists
  • Quinolines
  • Malondialdehyde
  • Peroxidase
  • Glutathione
  • montelukast