The DOI matches its Crossref record; 304 of the 308 references it cites were found in a registry or an index.
Pathophysiology of circulating xanthine oxidoreductase: New emerging roles for a multi-tasking enzyme
Open accessAbstract
The enzyme xanthine oxidoreductase (XOR) catalyses the last step of purine degradation in the highest uricotelic primates as a rate-limiting enzyme in nucleic acid catabolism. Although XOR has been studied for more than a century, this enzyme continues to arouse interest because its involvement in many pathological conditions is not completely known. XOR is highly evolutionarily conserved; moreover, its activity is very versatile and tuneable at multiple-levels and generates both oxidant and anti-oxidant products. This review covers the basic information on XOR biology that is essential to understand its enzymatic role in human pathophysiology and provides a comprehensive catalogue of the experimental and human pathologies associated with increased serum XOR levels. The production of radical species by XOR oxidase activity has been intensively studied and evaluated in recent decades in conjunction with the cytotoxic consequences and tissue injuries of various pathological conditions. More recently, a role has emerged for the activity of endothelium-bound enzymes in inducing the vascular response to oxidative stress, which includes the regulation of pro-inflammatory and pro-thrombotic activities of endothelial cells. The possible physiological functions of circulating XOR and the products of its enzyme activity are presented here together with their implications in cardiovascular and metabolic diseases.
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“The binding of plasma XO to ECs can lead to vascular dysfunction (45, 71, 562, 612, 1010).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [71]
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Cites
1 retracted
Aoki, N. (2006) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.60142 · Cited by 48 · cited 1×
“as a membrane-associated protein in the secretion of milk lipids during lactation in mice [87,88] (reviewed in [89]).”
BackgroundRetractedOxygen-Derived Free Radicals in Postischemic Tissue Injury
Epstein, F. H., & McCord, J. M. (1985) · New England Journal of Medicine · doi:10.1056/nejm198501173120305 · Cited by 5,399 · cited 2×
“In particular, attention has been focused on the role of XOR-derived ROS in the pathogenesis of tissue lesions induced by reperfusion after ischaemia (reviewed in [16,146]).”
BackgroundEndothelial dysfunction in cardiovascular diseases: the role of oxidant stress
Cai, H., & Harrison, D. G. (2000) · Circulation Research · doi:10.1161/01.res.87.10.840 · Cited by 3,839
Ames, B. N., Cathcart, R., Schwiers, E., & Hochstein, P. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.11.6858 · Cited by 2,915 · cited 1×
“advantage for uricotelic primates over ureotelic mammals [36] (reviewed in [37]).”
BackgroundUric Acid and Cardiovascular Risk
Feig, D. I., Kang, D., & Johnson, R. J. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0800885 · Cited by 2,467
Elevated Uric Acid Increases Blood Pressure in the Rat by a Novel Crystal-Independent Mechanism
Mazzali, M., Hughes, J., Kim, Y.-G., Jefferson, J. A., Kang, D., GORDON, K. L., Lan, H. Y., Kivlighn, S. D., & Johnson, R. J. (2001) · Hypertension · doi:10.1161/hy1101.092839 · Cited by 1,298 · cited 1×
“either by inhibiting XOR activity, which produces uric acid, or by inducing uricosuria, which eliminates uric acid [281,282].”
BackgroundPacher, P., Nivorozhkin, A., & Szabó, C. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.1.6 · Cited by 1,218 · cited 3×
“same purpose, the XOR inhibitor allopurinol has been used in many experimental and clinical studies (reviewed in [150]).”
BackgroundInfluentialThe Reduction of Cytochrome c by Milk Xanthine Oxidase
McCord, J. M., & Fridovich, I. (1968) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)91929-0 · Cited by 1,196 · cited 1×
“When oxygen is the electron acceptor, the reaction occurs via a one-electron reduction, producing superoxide ions [13], and a two-electron reduction, generating hydrogen peroxide (reviewed in [12]).”
BackgroundA causal role for uric acid in fructose-induced metabolic syndrome
Nakagawa, T., Hu, H., Zharikov, S. I., Tuttle, K. R., Short, R., Glushakova, O. Y., Ouyang, X., Feig, D. I., Block, E. R., Herrera-Acosta, J., et al. (2005) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00140.2005 · Cited by 1,111 · cited 1×
“prevented with allopurinol or reversed with a uricosuric agent [284] (reviewed in [272,285]).”
BackgroundJohnson, R. J., Segal, M. S., Sautin, Y., Nakagawa, T., Feig, D. I., Kang, D.-H., Gersch, M. S., Benner, S., & Sánchez-Lozada, L. G. (2007) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.4.899 · Cited by 1,075
Flagged first, then by citations
4 of the 308 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Nguyen, 1986, Plant xanthine dehydrogenase: its distribution, properties and function, Physiol. Vég., 24, 263
Cited by
Sorted by citations
Sharifi-Rad, M., Anil Kumar, N. V., Zucca, P., Varoni, E. M., Dini, L., Panzarini, E., Rajkovic, J., Tsouh Fokou, P. V., Azzini, E., Peluso, I., et al. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00694 · Cited by 1,971
Self-citationReperfusion injury and reactive oxygen species: The evolution of a concept
Granger, D. N., & Kvietys, P. R. (2015) · Redox Biology · doi:10.1016/j.redox.2015.08.020 · Cited by 1,550
“The binding of circulating XO to vascular endothelial cells has been invoked to explain the effectiveness of xanthine oxidase inhibitors in blunting the I/R injury response in tissues that exhibit low XO activity [131].”
BackgroundIncalza, M. A., D’Oria, R., Natalicchio, A., Perrini, S., Laviola, L., & Giorgino, F. (2017) · Vascular Pharmacology · doi:10.1016/j.vph.2017.05.005 · Cited by 1,419
“Finally, it should be mentioned that under specific pathological conditions, such as liver and intestine diseases [80] and hypoxia [81], XDH is released to the circulation and converted to the XO form that binds to”
BackgroundClinical Relevance of Biomarkers of Oxidative Stress
Frijhoff, J., Winyard, P. G., Žarković, N., Davies, S. S., Stocker, R., Cheng, D., Knight, A. R., Taylor, E., Oettrich, J., Ruskovska, T., et al. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6317 · Cited by 918
“This led to several, ongoing clinical trials with XO inhibitors in CVD and prompted many studies to measure circulating XO (12).”
ResultSources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541
Metadata
- Authors
- Battelli, M. G., Bolognesi, A., & Polito, L.
- Affiliations
- University of Bologna (IT)
- Corresponding author
- Bolognesi, Andrea
- Polito, Letizia
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 1842
- Issue
- 9
- Pages
- 1502-1517
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W2073007450
- Cited by
- 256
- References
- 308
- Citations by year
- 2026: 15 · 2025: 10 · 2024: 23 · 2023: 29 · 2022: 20 · 2021: 30 · 2020: 30 · 2019: 24 · 2018: 20 · 2017: 21 · 2016: 16 · 2015: 17 · 2014: 1
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, cc-by-nc-nd)
- Funders
- Alma Mater Studiorum‐University of Bologna
- Pallotti Legacies for Cancer Research
- Topics
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- xanthine oxidoreductase, purine degradation, uric acid, oxidative stress, reactive oxygen species, endothelial cells, vascular response, inflammation, thrombosis, cardiovascular disease, metabolic disorders, serum enzyme levels
- MeSH terms
- Animals, Cardiovascular Diseases, Humans, Xanthine Dehydrogenase, Metabolic Syndrome
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