Role of oxidants and antioxidants in diabetic wound healing

Abstract It has been extremely difficult to study the mechanisms involved in the development of chronic wounds because they do not contain a single defect. One of the critical parameters for proper healing is the redox state of the wound. The redox state is maintained by a balance between oxidant and antioxidant molecules. Oxidative stress (OS) is present in tissues and cells when there is an imbalance between the levels of reactive oxygen species (ROS) and the ability of antioxidants in the tissues and cells to remove these species and repair the damage they cause. Low levels of ROS are important for initiation and progression of proper healing, whereas high levels of ROS derail the cell and molecular mechanisms involved in healing leading to cell death and paralyzes of the healing process. Antioxidants inactivate reactive species by donating their electrons to these species and preventing them from capturing electrons from other important molecules such as DNA, proteins, and lipids. When the levels of antioxidant molecules are not sufficient to detoxify the cells and tissues from excessive OS, damage occurs. Examples of reactive radical forms of O2 are superoxide (O2•−), hydroxyl (•OH), and peroxyl (LOO•), whereas examples of nonradical reactive forms are hydrogen peroxide (H2O2), hypochlorous acid (HClO), and peroxynitrite (ONOO). Antioxidants can work through enzymatic or nonenzymatic reactions that can occur intracellularly in the cytosol and/or in organelles such as the mitochondria or in the extracellular environment. Chronic wounds in humans have high levels of OS. This is particularly true for chronic wounds of diabetic patients. A better understanding of how wounds become chronic is critical for future success in the treatment of such wounds after debridement. Because high levels of OS are present in chronic wounds and are critical for chronic wound initiation and development, we speculate that treatment of human chronic wounds with antioxidants both systemically and locally after debridement, coupled with other treatments such as antibiotics, may be effective in resolving chronicity.