The Promising Effect of Colchicine on Random-Pattern Skin Flap Survival in Rats: Glutamate Pathway.

Abstract

Random-pattern skin flap is a conventional procedure in reconstructive surgery, yet partial or complete flap necrosis has remained a major issue. Herein, we investigated the potential effects of colchicine on skin flap survival through the glutamate pathway and N-methyl-D-aspartate (NMDA) receptors. Wistar male rats were injected multiple doses of colchicine intraperitoneally (0.02, 0.05, 0.1, and 0.4mg/kg) before the surgery. MK-801 (a noncompetitive NMDA receptor antagonist) was administered in combination with colchicine to assess the role of glutamate. Histopathological evaluation; quantitative assessment of glutamate, IL-6, and TNF-α; and the expression of NR2A-type NMDA receptors were performed in the skin tissue. Colchicine 0.05mg/kg could significantly promote flap survival compared to the control group (P<0.001), while administration of MK-801 (0.05mg/kg) reversed the effect of colchicine (0.05mg/kg) (P<0.001). Levels of IL-6 and TNF-α decreased, and the expression of NR2A-type NMDA receptors was enhanced in the flap tissue of colchicine 0.05mg/kg group compared to the controls. Also, glutamate level significantly increased after the administration of colchicine 0.05mg/kg compared to the controls (P<0.05). We found that colchicine could improve skin flap survival remarkably in rats that have undergone skin flap surgery through the glutamate pathway and NMDA receptors.