Abstract
The development of novel local therapies for thermal burns (TB) and their pathogenetic rationale are a pressing challenge. Melatonin (MT) is an endogenous factor of hemostasis regulation with pleiotropic potential. The aim of this study was to assess some parameters of tissue regeneration, the functional state of mast cells and the levels of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the experimentally induced TB treated with the original MT-enriched dermal film (DF). A second-degree burn (3.5% of the total body surface area) was modelled by exposing a patch of skin to hot water. Applications of 12 cm2 DF enriched with 5 mg/g MT were performed every day for 5 days. The following parameters were calculated: the wound area, the rate of wound epithelization, the number of MC in the wound, the intensity of degranulation, and the levels of MMP-9 and VEGF expression. Over the course of treatment, the absolute wound area shrank by 35%, its epithelization rate increased, the number of MC rose, their functional state changed, and the expression of ММР-9 and VEGF increased. A negative correlation was established between the wound area and the expression of ММР-9 and VEGF, as well as between the wound area and the degranulation coefficient. Applications of MT-enriched DF resulted in the reduction of the wound area, higher epithelization rate, an increase in the total MC count and degranulation intensity on days 5 and 10; it also led to a reduction in the total MC count and a loss in degranulation intensity on day 20 (166.87 (154.95; 178.78) un/mm2 vs. 464.84 (452.92; 476.76) un/mm2) in the group of intact animals), an increase in MMP-9 expression on day 5 (14.20 (11.30; 18.10) vs. 3.30 (2.20; 4.40) in the intact group), an increase in VEGF expression on days 5 and 10 (33.00 (30.20; 34.90) vs 25.40 (22.20; 29.30) in the intact group), and a reduction in MMP-9 expression on days 10 and 20 after thermal injury.
Highlights
The absolute area of the experimentally induced burn shrank by 35% from day 5 to day 20, the wound epithelization rate and the total Mast cells (MC) count in the wound increased, and the functional activity of MC changed: the cells lost their granularity and underwent significant degranulation
A negative correlation was established between the wound area and the expression of ММР-9 and vascular endothelial growth factor (VEGF); the wound area and the degranulation coefficient were negatively correlated
The obtained results expand our knowledge of the contribution of changes in MC activity and the dynamics of matrix metalloproteinase-9 (MMP-9) and VEGF expression to the pathogenesis of thermal burns (TB)
Summary
Despite significant advances in the therapy of burns (skin grafting, stem cell therapy, etc.), slow wound healing, infection and scarring still pose a serious therapeutic challenge as they result in prolonged hospital stay, disfigurement, reduced quality of life, and emotional distress [2]. This can be largely explained by the complexity and diversity of pathogenetic mechanisms underlying the response to heat exposure and the progression and outcomes of thermal burns (TB). The aim of this study was to assess some parameters of tissue regeneration, the functional state of mast cells and the levels of MMP-9 and VEGF in the experimentally induced thermal burn treated with an original MT-enriched dermal film
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