Female, but not male, mice show delayed cutaneous wound healing following aspirin administration

Abstract

Cyclo-oxygenase (COX) is an enzyme that participates in the wound healing process. Aspirin, a non-steroidal anti-inflammatory drug, simultaneously inhibits the aromatase activity of COX-1 and COX-2 isoforms, which is needed for prostaglandin synthesis. The aim of the present study was to determine whether aspirin, and thus COX inhibition, distinctly affects cutaneous wound healing in female and male mice. Female and male BALB/c mice were treated with aspirin (25 mg/kg per day) for 16 days until they were killed. The control group received vehicle (saline) only. A full-thickness excisional lesion was made on the back, 2 days after aspirin administration started, and macroscopic, histological and biochemical parameters were evaluated. Sections were stained and immunostained for microscopic analysis. Myeloperoxidase (MPO) activity, hydroxyproline quantity and the protein expression of von Willebrand factor (vWF) and vascular endothelial growth factor (VEGF) were also determined. Female control and aspirin-treated groups exhibited delayed wound closure and re-epithelization compared with the male control and aspirin-treated groups, respectively. The female control group exhibited reduced MPO activity and a decreased number of macrophage inhibitory factor-positive cells compared with the male control group. In the female aspirin-treated group, MPO activity and the number of F4/80-positive macrophages was higher than in the control group. Collagen was reduced only in the female aspirin-treated group. The expression of vWF and VEGF protein was increased in the female aspirin-treated group. In conclusion, aspirin administration impaired the wound healing process in BALB/c female, but not male, mice.