Montelukast Protects Axial Pattern Rat Skin Flaps Against Ischemia/reperfusion Injury

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.