Investigation of the effect of metformin on the burns stasis zone

A burn is defined as a burn wound on the skin as a result of heat exposure injuries. Burns are a common serious problem. The burn wound causes both local effects at and around the injury site and a general response involving the whole body. Local effects in the burned area and all systemic effects that may occur in any part of the body are continuous without a clear point of separation. The complex nature of the burn wound is a challenging issue for all physicians dealing with burns. Therefore, the burn experience of the physician is very important. A better understanding of the pathophysiological changes in burns and studies on these issues allow for more success in burn treatment. If suitable conditions are provided and pathological changes can be stopped, necrosis of cells in the stasis zone can be prevented. Jackson divided the burn into three different zones based on the severity of the destruction and changes in blood flow. In the outer periphery, there is a zone of hyperemia with increased blood flow. In the center, there is the area called the coagulation zone, which is characterized by coagulation necrosis. Between these two regions, there is a zone of stasis in which ischemia tissues are present and cell and tissue damage is reversible in the early period. It should not be delayed in the supportive treatment of the patient so that the cells in the stasis zone do not lose their vitality and become necrosis. Many molecules have been experimentally investigated to recover the stasis zone and many studies are in progress. Current studies on burns in recent years are mostly about salvaging the zone of stasis. The aim of this study is to find an effective and cost-effective solution for the recovery of the stasis zone. Autophagy is defined as the production of energy and nutrients by the self-digesting of damaged cells and thus supporting the survival of other cells. It is known that autophagy decreases in the first 48 hours in the stasis zone in burnt skin compared to normal skin. Thermal damage in the burn and reactive oxygen derivatives formed in the burn area increase cell death, cells can obtain energy by digesting damaged organelles with autophagy and get rid of cell death. Many studies have shown that metformin induces autophagy by activation of AMPK (adenosine monophosphate with activated protein kinase). We aimed to save the reversible zone of stasis by increasing the decreased autophagy in the burned skin with metformin in the pathophysiology of burns. In this study, 20 Sprague-Dawley type rats were used, each group of 10 subjects. Cutaneous burn wound was created with a brass plate on the backs of both groups in accordance with the Comb burn model. The first group was determined as the control group. No drug was administered to the control group. The second group was determined as the experimental group and 100 mg/kg of metformin was administered daily starting from the first day after the burn model was created. Biopsies were taken from the rats at the end of the 24th hour and at the end of the 7th day, and histopathological, immunohistochemical and tunnel test studies were performed. At the end of the 7th day, the rats were sacrificed. Inflammation intensity, ulceration, epithelialization, necrosis and edema were measured as histopathological parameters. When the experimental group was compared with the control group, tissue damage was found to be low in all histopathological parameters in the experimental group. Beclin-1 and AMPKa1 antibodies were measured immunohistochemically. Antibody measurements were found to be significantly higher in the experimental group at the 24th hour and 7th day compared to the control group. Tunnel test was done only at 24 hours. The apoptosis rate determined in the experimental group was found to be lower than the control group. As a result of our study, it was shown that metformin increased autophagy, decreased apoptosis and decreased inflammation intensity in the experimentally created stasis zone model in rats, and had a positive effect on the recovery of the stasis zone. Further clinical and experimental studies are needed on this subject. Key words: Zone of stasis, metformin, burn, autophagy