Uric Acid and Xanthine Oxidoreductase in Wound Healing

Published on Feb 1, 2014in Current Rheumatology Reports 3.08
· DOI :10.1007/s11926-013-0396-1
Melissa Laura Fernandez3
Estimated H-index: 3
(Queensland University of Technology),
Zee Upton29
Estimated H-index: 29
(Queensland University of Technology),
Gary K. Shooter8
Estimated H-index: 8
(Queensland University of Technology)
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.
  • References (86)
  • Citations (7)
Published on Nov 1, 1998in Blood 15.13
Mark B. Hampton46
Estimated H-index: 46
Anthony J. Kettle46
Estimated H-index: 46
Christine C. Winterbourn67
Estimated H-index: 67
IN THE 1880s Elie Metchnikoff observed specialized phagocytic cells ingesting bacteria, and recognized the importance of phagocytosis as a defense mechanism in multicellular organisms.[1][1] Neutrophils are one of the professional phagocytes in humans. They ingest bacteria into intracellular
1,211 Citations
Published on Sep 1, 1995in Journal of Immunology 4.54
D A Bullough5
Estimated H-index: 5
M J Magill1
Estimated H-index: 1
+ 1 AuthorsKevin M. Mullane24
Estimated H-index: 24
Inhibition of neutrophil-myocyte adhesion and adhesion-dependent myocyte injury by adenosine was evaluated using isolated TNF-alpha-activated canine cells. Adenosine inhibited adhesion of activated neutrophils to cardiac myocytes with an IC50 of 11 +/- 4 nM. Inhibition of neutrophil adhesion (92 +/-3% by 100 nM adenosine) led to inhibition of myocyte injury (by 90 +/- 6%, as assessed by dye exclusion). Inhibition of cell adhesion by adenosine was blocked by the A2 antagonist, 1,3-dimethyl-1-prop...
60 Citations
Published on Mar 1, 1961in Annals of Internal Medicine 19.38
Daniel J. McCarty49
Estimated H-index: 49
Joseph Lee Hollander9
Estimated H-index: 9
325 Citations Source Cite
Published on May 1, 1993in The EMBO Journal 10.56
M. Meyer1
Estimated H-index: 1
(Ludwig Maximilian University of Munich),
R. Schreck1
Estimated H-index: 1
(Ludwig Maximilian University of Munich),
Patrick A. Baeuerle9
Estimated H-index: 9
(Ludwig Maximilian University of Munich)
We show that AP-1 is an antioxidant-responsive transcription factor. DNA binding and transactivation by AP-1 were induced in HeLa cells upon treatment with the antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC), and upon transient expression of the antioxidative enzyme thioredoxin. While PDTC and NAC enhanced DNA binding and transactivation of AP-1 in response to phorbol ester, the oxidant H2O2 suppressed phorbol ester activation of the factor. H2O2 on its own was only...
1,174 Citations Source Cite
Published on May 1, 1986in Biochemical Journal 3.86
Kelvin J.A. Davies87
Estimated H-index: 87
Alex Sevanian56
Estimated H-index: 56
+ 1 AuthorsP Hochstein1
Estimated H-index: 1
In order to survive in an oxygen environment, aerobic organisms have developed numerous mechanisms to protect against oxygen radicals and singlet oxygen. One such mechanism, which appears to have attained particular significance during primate evolution, is the direct scavenging of oxygen radicals, singlet oxygen, oxo-haem oxidants and hydroperoxyl radicals by uric acid. In the present paper we demonstrate that another important ‘antioxidant’ property of uric acid is the ability to form stable c...
373 Citations Source Cite
Published on Nov 14, 2012in Cochrane Database of Systematic Reviews 6.75
Susan O'Meara22
Estimated H-index: 22
(University of York),
Nicky Cullum48
Estimated H-index: 48
(University of Manchester)
+ 1 AuthorsJo C Dumville34
Estimated H-index: 34
(University of York)
Venous leg ulcers can occur when blood returning from veins in the legs to the heart is slow or obstructed. These ulcers can take a long time to heal (weeks or months) and can cause distress to patients, as well as being very costly to the health service. Compression bandages help blood to return to the heart from the legs, and there are a variety of types of bandage systems available; some are just a single bandage, while others require the application of several different types of bandages to ...
566 Citations Source Cite
Published on Apr 1, 1992in Journal of Immunology 4.54
Bruce N. Cronstein64
Estimated H-index: 64
Richard I. Levin22
Estimated H-index: 22
+ 3 AuthorsGerald Weissmann43
Estimated H-index: 43
We have recently demonstrated that human neutrophils (PMN) possess two different classes of adenosine receptors (A1 and A2) that, when occupied, promote chemotaxis and inhibit the generation of reactive oxygen species (e.g., O2- and H2O2), respectively. We have previously demonstrated that adenosine protects endothelial cells (EC) from injury by stimulated neutrophils (PMN) both by diminishing generation of H2O2 and inhibiting adherence of PMN to EC. We therefore determined whether occupancy of ...
317 Citations
Published on Jul 1, 1998in Biochimica et Biophysica Acta 3.44
Susanna Page2
Estimated H-index: 2
(University of Bath),
Debbie Powell1
Estimated H-index: 1
(University of Bath)
+ 5 AuthorsRoger Harrison26
Estimated H-index: 26
(University of Bath)
Abstract Xanthine oxidoreductase (XOR) in human mammary epithelial cells was shown to have low true specific activity, similar to that in breast milk. Enzymic activity was increased in response to inflammatory cytokines; increases of 2–2.5-fold being seen with TNF- α and IL-1 β and of approximately 8-fold with IFN- γ . No significant increase was seen with IL-6. A combination of IFN- γ and TNF- α , or of these two cytokines plus IL-1 β , led to responses representing the sum of those obtained by...
71 Citations Source Cite
Published on Feb 1, 2007in Pharmacology & Therapeutics 10.38
György Haskó61
Estimated H-index: 61
(Rutgers University),
Pal Pacher89
Estimated H-index: 89
(National Institutes of Health)
+ 1 AuthorsE. Sylvester Vizi54
Estimated H-index: 54
Adenosine is an endogenous purine nucleoside that, following its release into the extracellular space, binds to specific adenosine receptors expressed on the cell surface. Adenosine appears in the extracellular space under metabolically stressful conditions, which are associated with ischemia, inflammation, and cell damage. There are 4 types of adenosine receptors (A1, A2A, A2B and A3) and all adenosine receptors are members of the G protein-coupled family of receptors. Adenosine receptors are e...
145 Citations Source Cite
Published on May 1, 1994in Journal of Investigative Dermatology 6.45
Douglas Darr13
Estimated H-index: 13
(Duke University),
Irwin Fridovich90
Estimated H-index: 90
(Duke University)
During the past 25 years, the field of free radical biology has germinated sprouted, and flowered. Free radicals derived from molecular oxygen, formerly of interest only to radiation chemists, are now known to play multiple roles in living systems. We will here consider the generalities of this held with some special focus on skin as a site of oxygen radical production and as a target upon which the damaging propensities of these radicals are exerted.
332 Citations Source Cite
  • References (86)
  • Citations (7)
Cited By7
Published on Sep 1, 2015in Microvascular Research 2.46
Laura Alejandra Ariza Orellano3
Estimated H-index: 3
(Universidade Federal de Minas Gerais),
Simone Aparecida de Almeida3
Estimated H-index: 3
(Universidade Federal de Minas Gerais)
+ 1 AuthorsSilvia Passos Andrade25
Estimated H-index: 25
(Universidade Federal de Minas Gerais)
Abstract Recent data has indicated that, besides its classical therapeutic indication in hyperurecemia and gout, xanthine oxidase inhibitors can be used to various forms of ischemia and other types of tissue and vascular injuries. We tested the hypothesis that allopurinol, an inhibitor of xanthine oxidase (XO), might modulate acute and/or chronic inflammatory angiogenesis induced by subcutaneous implantation of synthetic matrix in mice. C57/BL6 male mice (6–7 weeks) were implanted with polyether...
5 Citations Source Cite
Published on Jul 1, 2015in Electrochemistry Communications 4.66
Petar Kassal1
Estimated H-index: 1
(University of California, San Diego),
Jayoung Kim12
Estimated H-index: 12
(University of California, San Diego)
+ 4 AuthorsJoseph Wang122
Estimated H-index: 122
(University of California, San Diego)
Abstract Advanced wound care technologies need to evolve in response to the growing burden of chronic wounds on national healthcare budgets and the debilitating impact chronic wounds have on patient quality of life. We describe here a new type of smart bandage for determination of uric acid (UA) status, a key wound biomarker, formed by screen printing an amperometric biosensor directly on a wound dressing. Immobilized uricase, paired with a printed catalytic Prussian blue transducer, facilitates...
47 Citations Source Cite
Published on Jul 1, 2014in Expert Review of Molecular Diagnostics 3.33
Ferdinando Mannello30
Estimated H-index: 30
Daniela Ligi8
Estimated H-index: 8
+ 1 AuthorsJoseph D. Raffetto27
Estimated H-index: 27
(Brigham and Women's Hospital)
Chronic venous disease represents a healthcare problem due to high prevalence and recurrence rates. Studies on chronic venous ulcer wound fluid (CVUWF) have demonstrated increased inflammation and proteolysis which can cause tissue destruction and delayed healing. This review discusses: nearly all known metabolites discovered in the past 25 years in CVUWF studies; the omics approaches characterizing the microenvironment of human venous leg ulcers; and the use of biocompounds as prognostic biomar...
16 Citations Source Cite
Published on Jan 1, 2015in Molecular Medicine 3.34
Michael C. Madigan4
Estimated H-index: 4
(University of Pittsburgh),
Ryan McEnaney6
Estimated H-index: 6
(University of Pittsburgh)
+ 6 AuthorsEdith Tzeng37
Estimated H-index: 37
(University of Pittsburgh)
Chronic, nonhealing wounds result in patient morbidity and disability. Reactive oxygen species (ROS) and nitric oxide (NO) are both required for normal wound repair, and derangements of these result in impaired healing. Xanthine oxidoreductase (XOR) has the unique capacity to produce both ROS and NO. We hypothesize that XOR contributes to normal wound healing. Cutaneous wounds were created in C57Bl6 mice. XOR was inhibited with dietary tungsten or allopurinol. Topical hydrogen peroxide (H2O2, 0....
10 Citations Source Cite
Published on Jun 1, 2017in International Journal of Rheumatic Diseases 2.42
Philip C. Robinson24
Estimated H-index: 24
(University of Queensland),
Sarina Kempe1
Estimated H-index: 1
(Monash Medical Centre)
+ 1 AuthorsLynden Roberts11
Estimated H-index: 11
(Monash University)
Aim To assess the epidemiology of inpatient gout in Australia and New Zealand during the years 2009–2014. Methods Using the Health Roundtable Limited (HRT) dataset, all patients with a coded ICD10 primary or secondary discharge diagnosis of gout from a HRT participating Australian or New Zealand hospital between the years 2009 and 2014 were identified. The number of inpatient gout admissions, length of stay, body site of gout flare, temporal trends and comorbidities were assessed. Results During...
3 Citations Source Cite
Published on Oct 1, 2018in Biosensors and Bioelectronics 8.17
Aniket Pal2
Estimated H-index: 2
(Purdue University),
Debkalpa Goswami5
Estimated H-index: 5
(Purdue University)
+ 3 AuthorsRamses V. Martinez20
Estimated H-index: 20
(Purdue University)
Abstract The growing socio-economic burden of chronic skin wounds requires the development of new automated and non-invasive analytical systems capable of wirelessly monitoring wound status. This work describes the low-cost fabrication of single-use, omniphobic paper-based smart bandages (OPSBs) designed to monitor the status of open chronic wounds and to detect the formation of pressure ulcers. OPSBs are lightweight, flexible, breathable, easy to apply, and disposable by burning. A reusable wea...
5 Citations Source Cite
Published on Jul 20, 2018in Pharmaceuticals
Mayara Amoras Teles Fujishima1
Estimated H-index: 1
Nayara S. R. Silva1
Estimated H-index: 1
+ 6 AuthorsCleydson Breno Rodrigues dos Santos8
Estimated H-index: 8
Reactive oxygen species (ROS) are continuously generated in the normal biological systems, primarily by enzymes as xanthine oxidase (XO). The inappropriate scavenging or inhibition of ROS has been considered to be linked with aging, inflammatory disorders, and chronic diseases. Therefore, many plants and their products have been investigated as natural antioxidants for their potential use in preventive medicine. The leaves and bark extracts of Curatella americana Linn. were described in scientif...
3 Citations Source Cite
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