期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 764, 期 -, 页码 9-21出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2015.06.029
关键词
Deferoxamine; Cytokines; Growth factors; Angiogenesis; Diabetic rats; Wound healing
Deferoxamine has shown cutaneous wound healing potential by increased neovascularizat on. 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-clepenclent 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-1 alpha), vascular endothelial growth factor (VEGF), stromal cell derived factor 1-alpha (SDF-1 alpha), transforming growth factor beta 1 (TGF-beta(1)), tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-9 (MMP-9), interleukin-1 beta (IL-1 beta) and interleukin-10 (IL-10) mRNA and proteins were determined in the wound tissues. CD 31 staining and collagen content were evaluated by immunohistochernistry and picrosirius red staining, respectively. Histological changes were assessed by H&E staining. The per cent wound closure was significantly higher from clay 7 onwards in deferoxamine-treated rats. HIF-1 alpha, VEGF, SDF-1 alpha, TGF-beta(1), IL-10 mRNA and their protein levels were significantly higher on days 3, 7 and 14 in deferoxarnine-treated rats. The rnRNA expression and protein levels of TNF-alpha, MMP-9 and IL-1 beta were progressively and markedly reduced in deferoxaminc-treated rats. The collagen deposition and formation of blood vessels were greater in deferoxaminc-treated rats. It is suggested that topical application of deferoxamine ointment might be useful in cutaneous wound healing in diabetic patients. (C) 2015 Elsevier B.V. All rights reserved.
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