Xanthine Oxidoreductase: A Novel Therapeutic Target for the Treatment of Chronic Wounds?

Significance: Chronic wounds are a major burden to patients and to healthcare systems worldwide. These wounds are difficult to heal and treatment is often lengthy and expensive. This has led to research efforts focussed on the wound environment attempting to understand the underlying pathological mechanisms of impaired wound healing. While some of this research has translated to advancements in wound therapies and implementation of new treatment options, chronic wounds remain a significant challenge to treat. Thus, identification of effective, low-cost, advanced wound therapies that enhance healing rates of these problematic wounds is still essential. Recent Advances and Critical Issues: Xanthine oxidoreductase (XOR), a molybdoflavin enzyme, is emerging as an important source of reactive oxygen species (ROS) in various pathologies, including diabetes and chronic wounds. XOR has recently been shown to be upregulated in chronic wounds, stimulating the overproduction of ROS during dysfunctional wound healing. XOR-induced ROS can amplify and potentiate inflammation in the wound environment further delaying wound closure. Future Directions: The detrimental role of XOR in impaired healing indicates it may be a therapeutic target. Targeted inhibition of XOR has been shown to reduce the expression and activity of this enzyme in diabetic wound models. In turn, this resulted in a significant decrease in ROS levels in the wound environment and improved wound healing. Therefore, repurposing existing XOR inhibitors that are approved for human use may be able to restore homeostasis at the wound site and enable damaged tissue to return to normal healing.