Uric Acid and Xanthine Oxidoreductase in Wound Healing

Abstract

Chronic wounds are an important health problem because they are difficult to heal and treatment is often complicated, lengthy and expensive. For a majority of sufferers the most common outcomes are long-term immobility, infection and prolonged hospitalisation. There is therefore an urgent need for effective therapeutics that will enhance ulcer healing and patient quality of life, and will reduce healthcare costs. Studies in our laboratory have revealed elevated levels of purine catabolites in wound fluid from patients with venous leg ulcers. In particular, we have discovered that uric acid is elevated in wound fluid, with higher concentrations correlating with increased wound severity. We have also revealed a corresponding depletion in uric acid precursors, including adenosine. Further, we have revealed that xanthine oxidoreductase, the enzyme that catalyses the production of uric acid, is present at elevated levels in wound fluid. Taken together, these findings provide evidence that xanthine oxidoreductase may have a function in the formation or persistence of chronic wounds. Here we describe the potential function of xanthine oxidoreductase and uric acid accumulation in the wound site, and the effect of xanthine oxidoreductase in potentiating the inflammatory response.

Validation of predictive factors for infection in adults with chronic leg ulcers: A prospective longitudinal study

“…Such inflammatory mediators play significant roles in inflammatory responses (Rider & Jordan, ; Zhao, Liang, Clarke, Jackson, & Xue, ). Furthermore, a study of 29 patients with CLUs by Fernandez, Upton, Edwards, Finlayson, and Shooter () found an increase in the level of uric acid in wound fluid was associated with increased severity of chronic venous leg ulcers (Fernandez et al, ; Fernandez, Upton, & Shooter, ). Thus, the current finding somewhat supports suggested links found in previous research.…”

“…Such inflammatory mediators play significant roles in inflammatory responses (Rider & Jordan, 2010;Zhao, Liang, Clarke, Jackson, & Xue, 2016). Furthermore, a study of 29 patients with CLUs by Fernandez, Upton, Edwards, Finlayson, and Shooter (2012) found an increase in the level of uric acid in wound fluid was associated with increased severity of chronic venous leg ulcers (Fernandez et al, 2012;Fernandez, Upton, & Shooter, 2014 Table 4). However, due to the limitation of small sample size and/ or the difference in the sample characteristics, two of the previously identified factors, depression and calf-ankle circumference ratio <1.3, were not able to be included in this multivariate analysis.…”

Epidemiology of inpatient gout in Australia and New Zealand: temporal trends, comorbidities and gout flare site

“…Consistent with the previous NZ research, infection was found to be a common cause for admission in those with gout. Recent work has suggested that urate may play a role in wound healing and potentially have wider impacts on inflammation …”

Chemical profiling of Curatella americana Linn leaves by UPLC-HRMS and its wound healing activity in mice

“…Inappropriate scavenging of these ROS generally results in a delay of wound healing, individuals with chronic leg ulcers and lesions due to ischemia present excessive production of oxygen radicals with significant xanthine oxidase activity [40].…”