The regulatory mechanism of deferoxamine spray in promoting the healing of chronic wounds in third-degree burns

Abstract

Objective To explore the effects and its mechanism of deferoxamine spray on the healing process of chronic wounds from third-degree burns. Methods Screening the concentration of deferoxamine spray suitable for subsequent experiments through cytotoxicity testing. The tube formation assay was used to assess the effect of deferoxamine spray on the angiogenic ability of human umbilical vein endothelial cells (HUVECs). The FerroOrange detection probe kit, reactive oxygen species (ROS) detection kit, and malondialdehyde (MDA) measurement kit were used to evaluate the effects of deferoxamine spray on intracellular ferrous ion (Fe2+) accumulation, intracellular reactive oxygen generation, and lipid oxidation reactions. The male SD rats were randomly divided into a control group and a deferoxamine spray treatment group. A chronic wound model of third-degree burns was established using a desktop hyperthermic burn machine, and the healing of the wounds was recorded through timed observations. Hematoxylin-Eosin and Masson staining were used to assess the re- epithelialization of the wound tissue and local collagen deposition, respectively. Immunohistochemical staining was performed to observe the expression of PECAM-1 (CD31), ferritin, and long-chain acyl-Coa synthetase 4 (ACSL4) proteins. Results A 5 μg/mL concentration of deferoxamine spray could significantly promote the angiogenesis of HUVECs, and significantly inhibited intracellular Fe2+ accumulation (P<0.001), reduced intracellular ROS generation (P<0.01), and decreased intracellular lipid oxidation reactions (P<0.001). In the chronic wounds of third-degree burn rats treated with deferoxamine spray, the restoration of skin integrity was faster (P<0.05), and more collagen was deposited (P<0.001). Compared to the control group, the expression of CD31 in the wound tissue of the deferoxamine spray treatment group was significantly increased (P<0.001), while ferritin expression and ACSL4 expression were significantly decreased (P<0.001). Conclusion Deferoxamine spray significantly promotes the healing of chronic wounds from third-degree burns in SD rats, and its mechanism may involve promoting angiogenesis, preventing intracellular iron accumulation, reducing ROS generation, decreasing lipid peroxidation reactions, and inhibiting the expression of ferroptosis pathways, thereby facilitating wound healing.

Keywords

• deferoxamine
• third-degree burns
• chronic wound healing
• ferroptosis