Deferoxamine modulates cytokines and growth factors to accelerate cutaneous wound healing in diabetic rats

Deferoxamine has shown cutaneous wound healing potential by increased neovascularization. We hypothesized that topically applied deferoxamine facilitates wound healing in diabetic rats by modulating important cytokines and growth factors that take part in healing processes in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin and wound was created under pentobarbitone anesthesia. The diabetic rats were divided into two groups, of which one (control) was treated with ointment base and other with deferoxamine ointment (0.1%). Wound closure measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor 1-alpha (SDF-1α), transforming growth factor beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-9 (MMP-9), interleukin-1 beta (IL-1β) and interleukin-10 (IL-10) mRNA and proteins were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histological changes were assessed by H&E staining. The per cent wound closure was significantly higher from day 7 onwards in deferoxamine-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and their protein levels were significantly higher on days 3, 7 and 14 in deferoxamine-treated rats. The mRNA expression and protein levels of TNF-α, MMP-9 and IL-1β were progressively and markedly reduced in deferoxamine-treated rats. The collagen deposition and formation of blood vessels were greater in deferoxamine-treated rats. It is suggested that topical application of deferoxamine ointment might be useful in cutaneous wound healing in diabetic patients.