Dexamethasone Improves Wound Healing by Decreased Inflammation and Increased Vasculogenesis in Mouse Skin Frostbite Model

Abstract

IntroductiondFrostbite is thought to result from initial vasoconstriction, ischemia, intracellular ice crystal formation, and inflammation caused by reperfusion injury. Corticosteroids have demonstrated beneficial anti-inflammatory effects in the treatment of other ischemia/reperfusion clinical conditions. The objective of this study was to determine the effect of dexamethasone (dex) on wound healing, inflammatory response, and vasculogenesis in a mouse skin frostbite model. MethodsdTreatment and control groups of C57/BL6 mice were subjected to frostbite using a previously described model. Treatment with intraperitoneal dex (1 mg$kg-1 $d-1) began on the day of frostbite induction and lasted for 7 d. Over 4 wk, we compared wound diameter; morphology by visual inspection, hematoxylineeosin staining, and Masson's trichrome staining; density of inflammatory cytokines IL-1b and TNFa using Western blot analysis; and formation of microvasculature using immunofluorescence staining. Data were analyzed using 1-way or 1-way repeated-measures analysis of variance. ResultsdAfter frostbite injury, morphological images demonstrated epidermal necrosis and loss in the frostbitten skin as well as infiltration of inflammation-related leukocytes. Increased production of inflammatory cytokines and disappearance of the microvasculature also occurred in the frostbitten skin. In comparison to the control group, treatment with dex promoted wound healing as demonstrated by decreased wound diameter; decreased levels of inflammatory cytokines, and accelerated formation of mature microvasculature. ConclusionsdIn this animal model, dex improved wound healing in frostbitten skin and demonstrated both anti-inflammatory effects and stimulation of vasculogenesis. This study suggests that the use of potent anti-inflammatory agents may be an effective strategy for mitigating frostbite injury.

Electrospun polylactic acid/sulfadiazine sodium/proteinase nanofibers and their applications in treating frostbite

“…(2) The model scientifically quantifies the affected skin surface area, histology, healing rate, and skin loss. [51][52][53] The proper compatibility between PLA and sulfadiazine sodium was shown in Figure 1, and the electros pun material containing sulfadiazine sodium has no adverse results in morphological properties. The fiber diameter of PLA/sulfadiazine sodium group and PLA/sulfadiazine sodium/proteinase K group were significantly reduced compared with that of PLA group under electron microscope and the treatment effect of these two groups on frostbite was uniform in different degrees, which was consistent with the results that the smaller fiber diameter had important value on cell adhesion and tissue proliferation reported in the previous literature.…”

A data mining and semantic analysis reveals novel insights into the genetic characteristics of the glucocorticoid receptor interactome

“…GCs can suppress the migration of endothelial progenitor cells (EPCs) and impair wound healing, something that should be considered before using EPCs for autologous cell transplantation (71). On the other hand, dexamethasone has been shown to be of assistance to wound healing in animal models of frostbite (72). Therefore, further studies are required to define the factors implicated in changing the GC wound healing properties.…”

Analysis of drug efficacy for inflammatory skin on an organ-chip system

“…To further demonstrate the possibility that the IC-SoC can be used to evaluate drug efficacy, skin inflammatory pathological drugs, polyphyllin (Wang et al, 2018) and dexamethasone (Tu et al, 2020), which had an inhibitory effect on inflammatory factors in previous studies, were used to test irritation-relevant responses in IC-SoC. First, tissue cellular viability was detected as shown in Supplementary Figure S5A.…”