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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Binding of plasma XO to ECs can lead to vascular dysfunction.
“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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1 retracted
Aoki, N. (2006) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.60142 · Cited by 48 · cited 1× · see citing works
“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× · see citing works
“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 · see citing works
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× · see citing works
“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 2,443 · see citing works
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× · see citing works
“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× · see citing works
“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 1,205 · cited 1× · see citing works
“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 1,104 · cited 1× · see citing works
“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 · see citing works
Uric Acid and Oxidative Stress
Glantzounis, G. K., Tsimoyiannis, E., Kappas, A. M., & Galaris, D. (2005) · Current Pharmaceutical Design · doi:10.2174/138161205774913255 · Cited by 1,043 · cited 1× · see citing works
“However, it should be noted that the final product of purine catabolism, uric acid, has an important role in vivo as an antioxidant (reviewed in [35]).”
BackgroundReactive species mechanisms of cellular hypoxia-reoxygenation injury
Li, C., & Jackson, R. M. (2002) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00112.2001 · Cited by 1,037 · cited 2× · see citing works
“In cells, hypoxia is able to induce numerousmetabolic alterations and the activation of transcriptional factors, including hypoxia-inducible factor-1 (HIF-1), nuclear factor-κB (NF-κB), and protein kinases, such as mitogenactivated protein kinase (MAPK) (reviewed in [110]).”
BackgroundUric Acid: The Oxidant-Antioxidant Paradox
Sautin, Y. Y., & Johnson, R. J. (2008) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1080/15257770802138558 · Cited by 981 · cited 1× · see citing works
“inflammatory effects, the latter function being exerted by the products of uric acid oxidation in the presence of peroxide [269].”
BackgroundFeig, D., Soletsky, B., & Johnson, R. J. (2008) · Journal of the American Medical Association (JAMA) · doi:10.1001/jama.300.8.924 · Cited by 936 · cited 1× · see citing works
“Moreover, allopurinol treatment resulted in blood pressure reduction in adolescents with newly diagnosed hypertension [288], although it is not clear if the benefit was due to XOR activity inhibition, uricaemia reduction, or the ROS scavenging activity of allopurinol (reviewed in [289]).”
BackgroundBerry, C. E., & Hare, J. M. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.055913 · Cited by 925 · cited 2× · see citing works
“advantage for uricotelic primates over ureotelic mammals [36] (reviewed in [37]).”
BackgroundRole of xanthine oxidase and granulocytes in ischemia-reperfusion injury
Granger, D. N. (1988) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1988.255.6.h1269 · Cited by 825 · see citing works
Structure and function of xanthine oxidoreductase: where are we now?
Harrison, R. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00956-5 · Cited by 787 · see citing works
Does superoxide underlie the pathogenesis of hypertension?
Nakazono, K., Watanabe, N., Matsuno, K., Sasaki, J., Sato, T., & Inoue, M. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.22.10045 · Cited by 746 · see citing works
The Regulation of Rat Liver Xanthine Oxidase
Stirpe, F., Corte, E. D., & Lorenzoni, E. (1969) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36428-1 · Cited by 733 · see citing works
Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression.
Rao, G., & Berk, B. C. (1992) · Circulation Research · doi:10.1161/01.res.70.3.593 · Cited by 653 · cited 1× · see citing works
“In addition to cytotoxicity and tissue damage, XOR-generated ROS are responsible for many biological activities, including iron mobilisation from ferritin in the liver [17], iron absorption in the intestinal mucosal [18], and the induction of proliferation [19–21] as well as defence against infectious diseases by cont…”
BackgroundXanthine oxidase: biochemistry, distribution and physiology.
Parks, D. A., & Granger, D. N. (1986) · PubMed · Cited by 638 · see citing works
Petrone, W. F., English, D. K., Wong, K. L., & McCord, J. M. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.2.1159 · Cited by 616 · cited 1× · see citing works
“Indeed, these oxidantsmay play a role in the cytotoxic activity of phagocytes either directly [22] by activating a chemotactic factor [23] and pro-collagenase [24], by increasing the adhesion of leukocytes [25] and cytokine production by monocytes [26], or by inducing the accumulation of leukocytes inmicrovasculature…”
BackgroundRole of Oxidative Stress in Myocardial Hypertrophy and Failure
Sawyer, D. B., Siwik, D. A., Xiao, L., Pimentel, D. R., Singh, K., & Colucci, W. S. (2002) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2002.1526 · Cited by 567 · cited 2× · see citing works
“present at high levels (reviewed in [243,267]).”
BackgroundDoehner, W., Schoene, N., Rauchhaus, M., Leyva‐Leon, F., Pavitt, D. V., Reaveley, D. A., Schuler, G. C., Coats, A. J. S., Anker, S. D., & Hambrecht, R. (2002) · Circulation · doi:10.1161/01.cir.0000017502.58595.ed · Cited by 565 · see citing works
Allopurinol Improves Endothelial Dysfunction in Chronic Heart Failure
Farquharson, C. A. J., Butler, R., Hill, A., Belch, J. J. F., & Struthers, A. D. (2002) · Circulation · doi:10.1161/01.cir.0000022140.61460.1d · Cited by 504 · cited 1× · see citing works
“capacity and blood flow locally and systemically in hyperuricaemic patients with chronic heart failure [258,259] and in patientswith coronary”
BackgroundXanthine oxidase and xanthine dehydrogenase
Hille, R., & Nishino, T. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.11.7649415 · Cited by 445 · see citing works
Corte, E. D., & Stirpe, F. (1972) · Biochemical Journal · doi:10.1042/bj1260739 · Cited by 437 · see citing works
Allopurinol Improves Myocardial Efficiency in Patients With Idiopathic Dilated Cardiomyopathy
Cappola, T. P., Kass, D. A., Nelson, G. S., Berger, R. D., Rosas, G. O., Kobeissi, Z. A., Marbán, E., & Hare, J. M. (2001) · Circulation · doi:10.1161/hc4501.098928 · Cited by 436 · cited 2× · see citing works
“enzyme activity by allopurinol administration resulted in a significant improvement in myocardial efficiency [151].”
BackgroundOxygen Radicals in Influenza-Induced Pathogenesis and Treatment with Pyran Polymer-Conjugated SOD
Oda, T., Akaike, T., Hamamoto, T., Suzuki, F., Hirano, T., & Maeda, H. (1989) · Science · doi:10.1126/science.2543070 · Cited by 418 · cited 1× · see citing works
“with inflammation, as reported in mice treated with the IFN inducer [90] or infected with influenza virus [170–172], in rats after thermal”
BackgroundImpact of Oxypurinol in Patients With Symptomatic Heart Failure
Hare, J. M., Mangal, B., Brown, J., Fisher, C., Freudenberger, R., Colucci, W. S., Mann, D. L., Liu, P., Givertz, M. M., & Schwarz, R. P. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.01.068 · Cited by 392 · see citing works
Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease
Aslan, M., Ryan, T. M., Adler, B., Townes, T. M., Parks, D. A., Thompson, J. A., Tousson, A., Gladwin, M. T., Patel, R. P., Tarpey, M. M., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.221292098 · Cited by 391 · cited 1× · see citing works
“intrahepatic hypoxia/reoxygenation, which can induce XOR release into the circulation from an injured liver [216].”
BackgroundXanthine Oxidase Is Involved in Free Radical Production in Type 1 Diabetes
Desco, C., Asensi, M. A., Márquez, R., Martínez-Valls, J. F., Vento, M., Pallardó, F. V., Sastre, J., & Viña, J. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1118 · Cited by 391 · cited 1× · see citing works
“skin injury [173–175], in cattle receiving LPS [176], in hypercholesterolaemic rabbits [177], in streptozotocin-induced diabetic rats [178] and”
BackgroundNishino, T., Okamoto, K., Eger, B. T., PAI, E. F., & Nishino, T. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06489.x · Cited by 387 · cited 3× · see citing works
“and slow (SH**) reacting (reviewed in [67]).”
BackgroundInfluentialBrain injury, edema, and vascular permeability changes induced by oxygen‐derived free radicals
Chan, P. H., Schmidley, J. W., Fishman, R. A., & Longar, S. (1984) · Neurology · doi:10.1212/wnl.34.3.315 · Cited by 382 · see citing works
White, C. R., Darley-Usmar, V, Berrington, W. R., McAdams, M., Gore, J. Z., Thompson, J. A., Parks, D. A., Tarpey, M. M., & Freeman, B. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8745 · Cited by 367 · see citing works
Remote Ischemic Preconditioning: A Novel Protective Method From Ischemia Reperfusion Injury—A Review
Tapuria, N., Kumar, Y., Habib, M. M., Abu‐Amara, M., Seifalian, A. M., & Davidson, B. R. (2008) · Journal of Surgical Research · doi:10.1016/j.jss.2007.12.747 · Cited by 359 · cited 1× · see citing works
“in distant organs, whereas high levels of ROS may activate a cascade of ischaemia/reperfusion injury (reviewed in [242]).”
BackgroundMendel, R. R., & Bittner, F. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.03.013 · Cited by 356 · cited 2× · see citing works
“in vivo by the XORmolybdenum cofactor sulphurase via the reinsertion of a sulphur atom at the active site (reviewed in [100]).”
BackgroundConversion of xanthine dehydrogenase to oxidase in ischemic rat tissues.
Engerson, T. D., McKelvey, T. G., Rhyne, D. B., Boggio, E. B., Snyder, S. J., & Jones, H. P. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112990 · Cited by 350 · see citing works
A comparison of the specificities of xanthine oxidase and aldehyde oxidase
Krenitsky, T. A., Neil, S. M., Elion, G. B., & Hitchings, G. H. (1972) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(72)90078-1 · Cited by 341 · cited 1× · see citing works
“compounds [7] (reviewed in [8]), and retinol [9].”
BackgroundAkaike, T., Ando, M., Oda, T., Doi, T., Ijiri, S., Araki, S., & Maeda, H. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114499 · Cited by 333 · see citing works
FRUCTOSE-INDUCED HYPERURICÆMIA
Stirpe, F., Corte, E. D., Bonetti, E., Abbondanza, A., Abbati, A., & Stefano, F. D. (1970) · The Lancet · doi:10.1016/s0140-6736(70)92269-5 · Cited by 331 · see citing works
Significance of xanthine oxidase in capillary endothelial cells.
Ed, J., Bruder, G., & Heid, H. (1986) · PubMed · Cited by 327 · see citing works
Redox signaling in cardiac myocytes
Santos, C. X. C., Anilkumar, N. P., Zhang, M., Brewer, A. C., & Shah, A. M. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.01.003 · Cited by 312 · cited 3× · see citing works
“6b), including detrimental effects, such as pathological hypertrophy or apoptosis, and protective effects, such as adaptive hypertrophy and angiogenesis (reviewed in [243]).”
BackgroundConversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation
Parks, D. A., Williams, T. K., & Beckman, J. S. (1988) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1988.254.5.g768 · Cited by 282 · cited 1× · see citing works
“Additionally, reversible or irreversible XDH/XO conversion was observed in a variety of hypoxic/ischaemic conditions in rat tissues, including the liver, kidney, heart, and lung [138], liver and kidney [139], intestine [140], liver [141], and brain [106,142–144].”
BackgroundUric acid and oxidative stress: Relative impact on cardiovascular risk
Strazzullo, P., & Puig, J. G. (2007) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2007.02.011 · Cited by 281 · see citing works
Akyol, Ö., Herken, H., Uz, E., Fadıllıoğlu, E., Ünal, S., Söğüt, S., Özyurt, H., & SAVAS, H. A. (2002) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(02)00220-8 · Cited by 278 · see citing works
The species distribution of xanthine oxidase
Al-Khalidi, U. A. S., & Chaglassian, T. (1965) · Biochemical Journal · doi:10.1042/bj0970318 · Cited by 272 · cited 1× · see citing works
“variation; in particular, a wide range of activity levels has been reported in biological fluids, such as blood [46] (reviewed in [47]) and milk (reviewed in [39]).”
BackgroundBinding of Xanthine Oxidase to Vascular Endothelium
Houston, M., Estévez, Á. G., Chumley, P. H., Aslan, M., Marklund, S. L., Parks, D. A., & Freeman, B. Α. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.8.4985 · Cited by 271 · cited 3× · see citing works
“Finally, endothelium-bound XOR activity was also able to inhibit endothelial NO production, thus impairing vasodilatory reaction [234].”
BackgroundInfluentialCharacterization of free radical generation by xanthine oxidase
Kuppusamy, P., & Zweier, J. L. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)81740-9 · Cited by 263 · cited 1× · see citing works
“cal and pathological conditions due to the formation of hydroxyl radicals in the presence of iron via the Haber–Weiss reaction [14], as is the case in acute iron intoxication [15].”
BackgroundReperfusion Injury as the Mechanism of Brain Damage after Perinatal Asphyxia
Fellman, V., & Raivio, K. O. (1997) · Pediatric Research · doi:10.1203/00006450-199705000-00001 · Cited by 259 · cited 1× · see citing works
“investigated in animal models by pre-treatment with tungsten, which inactivates XOR, to prevent organ damage (reviewed in [149]).”
BackgroundEkelund, U. E. G., Harrison, R. W., Shokek, O., Thakkar, R. N., Tunin, R. S., Senzaki, H., Kass, D. A., Marbán, E., & Hare, J. M. (1999) · Circulation Research · doi:10.1161/01.res.85.5.437 · Cited by 239 · cited 1× · see citing works
“in dogswith pacing-induced heart failure [251].”
Role of oxygen free radicals in shock, ischemia, and organ preservation.
Parks, D. A., Bulkley, G. B., & Granger, D. N. (1983) · PubMed · Cited by 236 · see citing works
Galli, A., Svegliati‐Baroni, G., Ceni, E., Milani, S., Ridolfi, F., Salzano, R., Tarocchi, M., Grappone, C., Pellegrini, G., Benedetti, A., et al. (2005) · Hepatology · doi:10.1002/hep.20683 · Cited by 235 · cited 1× · see citing works
“In addition to cytotoxicity and tissue damage, XOR-generated ROS are responsible for many biological activities, including iron mobilisation from ferritin in the liver [17], iron absorption in the intestinal mucosal [18], and the induction of proliferation [19–21] as well as defence against infectious diseases by cont…”
BackgroundRoles of histamine, complement and xanthine oxidase in thermal injury of skin.
Friedl, H. P., Till, G. O., Trentz, O., & Ward, P. A. (1989) · PubMed Central · Cited by 234 · see citing works
Meneshian, A., & Bulkley, G. B. (2002) · Microcirculation · doi:10.1038/sj.mn.7800136 · Cited by 225 · cited 1× · see citing works
“producing form of XOR in vivo could imply its well-studied pathological role of inducing tissue damage and the physiological function of triggering a microvascular inflammatory response through an oxidantmediated signal transduction (reviewed in [246]).”
BackgroundFree radical-mediated reperfusion injury: a selective review.
Bulkley, G. B. (1987) · PubMed · Cited by 220 · see citing works
Mediator‐induced activation of xanthine oxidase in endothelial cells
Friedl, H. P., Till, G. O., Ryan, U. S., & Ward, P. A. (1989) · The FASEB Journal · doi:10.1096/fasebj.3.13.2806779 · Cited by 218 · cited 1× · see citing works
“stimulation with C5a, TNF, a chemotactic N-formyl peptide [126] or activated neutrophils [127,128]; kainic acid [60] or glutamate neurotoxicity [129]; ricin hepatotoxicity [130]; in a rat model of nephropathy [131]; ultraviolet B radiation [132]; irradiation with gamma rays [133]; hepatocellular injury induced by iron…”
BackgroundGranger, D. N. (1999) · Microcirculation · doi:10.1111/j.1549-8719.1999.tb00099.x · Cited by 218 · cited 4× · see citing works
“Indeed, the inhibition of NO production by vascular XOR activity could explain how XOR released into plasma during diverse pathological processes may alter vascular functions via oxidative mechanisms by reducing vasodilatory responses (reviewed in [244]).”
BackgroundInfluentialGhosh, S. M., Kapil, V., Fuentes-Calvo, I., Bubb, K. J., Pearl, V., Milsom, A. B., Khambata, R., Maleki-Toyserkani, S., Yousuf, M., Benjamin, N., et al. (2013) · Hypertension · doi:10.1161/hypertensionaha.111.00933 · Cited by 218 · cited 1× · see citing works
“Thus, allopurinol treatment could suppress the blood pressurelowering effects of dietary nitrates [302].”
BackgroundVascular Dysfunction in Ischemia-Reperfusion Injury
Seal, J. B., & Gewertz, B. L. (2005) · Annals of Vascular Surgery · doi:10.1007/s10016-005-4616-7 · Cited by 217 · cited 1× · see citing works
“5b) (reviewed in [245]).”
Binding of human xanthine oxidase to sulphated glycosaminoglycans on the endothelial-cell surface
Adachi, T., Fukushima, T., Usami, Y., & Hirano, K. (1993) · Biochemical Journal · doi:10.1042/bj2890523 · Cited by 213 · cited 1× · see citing works
“the ability to stick to vascular cells because it binds to sulphated glycosaminoglycans on the endothelial cell surface [233].”
BackgroundVorbach, C., Scriven, A., & Capecchi, M. R. (2002) · Genes & Development · doi:10.1101/gad.1032702 · Cited by 211 · cited 1× · see citing works
“as a membrane-associated protein in the secretion of milk lipids during lactation in mice [87,88] (reviewed in [89]).”
BackgroundLandmesser, U., Spiekermann, S., Preuss, C., Sorrentino, S., Fischer, D., Manes, C., Mueller, M., & Drexler, H. (2007) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000258415.32883.bf · Cited by 210 · cited 1× · see citing works
“In patients with coronary disease, treatment with the AT1-receptor blocker losartan reduced endothelium-bound XOR activity and endothelial dysfunction [265].”
BackgroundXanthine oxidase type D (dehydrogenase) in the intestine and other organs of the rat
Battelli, M. G., Corte, E. D., & Stirpe, F. (1972) · Biochemical Journal · doi:10.1042/bj1260747 · Cited by 197 · cited 1× · see citing works
“(reviewed in [3]) until almost half a century ago, when mammalian XOR was shown to be a dehydrogenase in its native state [40,41].”
BackgroundSelf-citationSaavedra, W. F., Paolocci, N., John, M. E. S., Skaf, M. W., Stewart, G. C., Xie, J.-S., Harrison, R. W., Zeichner, J., Mudrick, D. W., Marbán, E., et al. (2002) · Circulation Research · doi:10.1161/hh0302.104531 · Cited by 196 · cited 1× · see citing works
“resulted in an imbalance between XOR activity and NOproduction, contributing to mechanoenergetic uncoupling in heart failure [252].”
BackgroundXanthine dehydrogenase/xanthine oxidase and oxidative stress
Chung, H. Y., Baek, B. S., Song, S. H., Kim, M. S., Huh, J. I., Shim, K. H., Kim, K. W., & Lee, K. H. (1997) · AGE · doi:10.1007/s11357-997-0012-2 · Cited by 194 · cited 1× · see citing works
“activity (reviewed in [39,43]).”
Ioachimescu, A. G., Brennan, D. M., Hoar, B. M., Hazen, S. L., & Hoogwerf, B. J. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23121 · Cited by 194 · cited 1× · see citing works
“cular disease [276].”
Role of Xanthine Oxidoreductase as an Antimicrobial Agent
Martin, H. M., Hancock, J. T., Salisbury, V. C., & Harrison, R. (2004) · Infection and Immunity · doi:10.1128/iai.72.9.4933-4939.2004 · Cited by 188 · cited 1× · see citing works
“The anti-microbial activity of XOR has been exhaustively reviewed in [33].”
BackgroundCirculating xanthine oxidase: potential mediator of ischemic injury
Yokoyama, Y., Beckman, J. S., Beckman, T. K., Wheat, J. K., Cash, T., Freeman, B. Α., & Parks, D. A. (1990) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1990.258.4.g564 · Cited by 188 · cited 2× · see citing works
“perfusate was similar to the paralleled decrease in endogenous tissue enzyme [192].”
BackgroundMammalian peroxisomes and reactive oxygen species
Schrader, M., & Fahimi, H. D. (2004) · Histochemistry and Cell Biology · doi:10.1007/s00418-004-0673-1 · Cited by 177 · see citing works
Hypoxia, reactive oxygen, and cell injury
de GROOT, H., & Littauer, A. (1989) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(89)90047-6 · Cited by 176 · see citing works
NADH Oxidase Activity of Human Xanthine Oxidoreductase
Sanders, S. A., Eisenthal, R., & Harrison, R. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00541.x · Cited by 170 · cited 2× · see citing works
“The bactericidal activity of XOR may be potentiated either by the possibility to act as an NADH oxidase [29–31] or by the ability to produce peroxynitrite [32].”
BackgroundCellular distribution, metabolism and regulation of the xanthine oxidoreductase enzyme system
Pritsos, C. A. (2000) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(00)00203-9 · Cited by 167 · see citing works
Dawson, J., & Walters, J. (2006) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2006.02785.x · Cited by 167 · cited 2× · see citing works
“indicated that uric acid reductionmay contribute to the reduction of risk (reviewed in [277,278]).”
BackgroundUric Acid Predicts Clinical Outcomes in Heart Failure
Hare, J. M., & Johnson, R. J. (2003) · Circulation · doi:10.1161/01.cir.0000066420.36123.35 · Cited by 165 · cited 2× · see citing works
“infarction, and cardiovascular death (reviewed in [273,274]).”
BackgroundHiggins, P., Dawson, J., Lees, K. R., McArthur, K., Quinn, T. J., & Walters, M. R. (2012) · Cardiovascular Therapeutics · doi:10.1111/j.1755-5922.2011.00277.x · Cited by 164 · see citing works
Oxidative Stress and Vascular Function: Implications for Pharmacologic Treatments
Weseler, A. R., & Bast, A. (2010) · Current Hypertension Reports · doi:10.1007/s11906-010-0103-9 · Cited by 161 · cited 1× · see citing works
“The main molecular sources of such oxidants in endothelial cells have been identified in NAD(P)H oxidase, xanthine oxidase, and NO synthase, which are involved in the dysregulation of the vascular redox environment that is associated with impaired vascular function and cardiovascular diseases (reviewed in [290]).”
BackgroundUmezawa, K., Akaike, T., Fujii, S., Suga, M., Setoguchi, K., Ozawa, A., & Maeda, H. (1997) · Infection and Immunity · doi:10.1128/iai.65.7.2932-2940.1997 · Cited by 154 · cited 1× · see citing works
“The inhibition of these enzyme activities resulted in the exacerbation of the infection, indicating their importance as anti-microbial leukocyte defences [98].”
BackgroundGonzález, D. R., Treuer, A. V., Castellanos, J. A., Dulce, R. A., & Hare, J. M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.154948 · Cited by 153 · cited 2× · see citing works
“cate that nitroso-redox disequilibrium at the sarcoplasmic reticulum level is due to oxidative stress, which is possibly dependent on XOR up-regulation [266].”
BackgroundMcKelvey, T. G., Höllwarth, M. E., Granger, D. N., Engerson, T. D., Landler, U., & Jones, H. P. (1988) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1988.254.5.g753 · Cited by 151 · cited 1× · see citing works
“Additionally, reversible or irreversible XDH/XO conversion was observed in a variety of hypoxic/ischaemic conditions in rat tissues, including the liver, kidney, heart, and lung [138], liver and kidney [139], intestine [140], liver [141], and brain [106,142–144].”
BackgroundWatts, R. W. E., Watts, J. E. M., & Seegmiller, J. E. (1965) · PubMed · Cited by 151 · see citing works
Ichida, K., Matsumura, T., Sakuma, R., Hosoya, T., & Nishino, T. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4719 · Cited by 151 · cited 1× · see citing works
“, XOR deficiency [104].”
Phan, S. H., Gannon, D. E., Varani, J., Ryan, U. S., & Ward, P. A. (1989) · PubMed Central · Cited by 147 · see citing works
Ischemia-reperfusion in humans. Appearance of xanthine oxidase activity.
Friedl, H. P., Smith, D. J., Till, G. O., Thomson, P. D., Louis, D. S., & Ward, P. A. (1990) · Europe PMC (PubMed Central) · Cited by 145 · see citing works
Pfeffer, K. D., Huecksteadt, T. P., & Hoidal, J. R. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.153.4.1789 · Cited by 145 · see citing works
Battelli, M. G., Lorenzoni, E., & Stirpe, F. (1973) · Biochemical Journal · doi:10.1042/bj1310191 · Cited by 144 · see citing works
Self-citationIchida, K., Amaya, Y., Nöda, K., Shinsei, M., Hosoya, T., Sakai, O., Shimizu, N., & Takeshi, N. (1993) · Gene · doi:10.1016/0378-1119(93)90652-j · Cited by 144 · see citing works
Uric Acid and Hypertension: Cause or Effect?
Mazzali, M., Kanbay, M., Segal, M. S., Shafiu, M., Jalal, D. I., Feig, D. I., & Johnson, R. J. (2010) · Current Rheumatology Reports · doi:10.1007/s11926-010-0094-1 · Cited by 142 · see citing works
Dehydrogenase conversion to oxidase and lipid peroxidation in brain after carbon monoxide poisoning
Thom, S. R. (1992) · Journal of Applied Physiology · doi:10.1152/jappl.1992.73.4.1584 · Cited by 140 · cited 1× · see citing works
“Additionally, reversible or irreversible XDH/XO conversion was observed in a variety of hypoxic/ischaemic conditions in rat tissues, including the liver, kidney, heart, and lung [138], liver and kidney [139], intestine [140], liver [141], and brain [106,142–144].”
BackgroundBaker, J. E., Su, J., Fu, X., Hsu, A., Gross, G. J., Tweddell, J. S., & Hogg, N. (2007) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2007.07.057 · Cited by 137 · see citing works
Dupont, G. P., Huecksteadt, T. P., Marshall, B. C., Ryan, U. S., Michael, J. R., & Hoidal, J. R. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115563 · Cited by 136 · cited 1× · see citing works
“Additionally, XOR activity was up-regulated by IFNγ in rat lung endothelial cells [93].”
BackgroundXanthine oxidase activity in the circulation of rats following hemorrhagic shock
Tan, S., Yokoyama, Y., Dickens, E., Cash, T., Freeman, B. Α., & Parks, D. A. (1993) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(93)90040-2 · Cited by 134 · cited 1× · see citing works
“to vascular lining was shown to be heparin reversible in studies with cultured endothelial cells [189].”
BackgroundMcManaman, J. L., Palmer, C. A., Wright, R. M., & Neville, M. C. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.027185 · Cited by 132 · cited 1× · see citing works
“until lactation followed by decreasing levels with mammary involution [84].”
BackgroundTerada, L. S., Dormish, J. J., Shanley, P. F., Leff, J. A., Anderson, B. O., & Repine, J. E. (1992) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1992.263.3.l394 · Cited by 130 · cited 2× · see citing works
“elevation after artery ligation in cats [181], rabbits [182–186], and rats [27,157,187,188] as well as after haemorrhagic shock in mice [26] and”
BackgroundAtlante, A., Gagliardi, S., Minervini, G. M., Ciotti, M. T., Marra, E., & Calissano, P. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68052038.x · Cited by 126 · see citing works
Enhanced Expression and Activity of Xanthine Oxidoreductase in the Failing Heart
de Jong, J. W., Schoemaker, R. G., de Jonge, R., Bernocchi, P., Keijzer, E., Harrison, R., Sharma, H. S., & Ceconi, C. (2000) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2000.1240 · Cited by 120 · see citing works
Sánchez‐Lozada, L. G., Tapia, E., Soto, V., Ávila-Casado, C., Franco, M., Zhao, L., & Johnson, R. J. (2007) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfm783 · Cited by 120 · cited 2× · see citing works
“sion, and hypertriglyceridaemia and prevented an increase in fasting plasma insulin in rats with fructose-induced metabolic syndrome [282].”
BackgroundTerao, M., Cazzaniga, G., Ghezzi, P., Bianchi, M., Francesco Falciani, B., Perani, P., & Garattini, E. (1992) · Biochemical Journal · doi:10.1042/bj2830863 · Cited by 117 · see citing works
Cingolani, H. E., Plastino, J. A. M., Escudero, E. M., Mangal, B., Brown, J., & Pérez, N. G. (2006) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2006.05.005 · Cited by 117 · cited 1× · see citing works
“The treatment significantly improved the left ventricular ejection fraction only in 21 patients who exhibited this initial parameter lower or equal to 40% [261].”
BackgroundHuman liver xanthine oxidase: Nature and extent of individual variation
Guerciolini, R., Szumlanski, C. L., & Weinshilboum, R. M. (1991) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1991.205 · Cited by 116 · cited 1× · see citing works
“Based on its levels of mRNA and protein expression, the highest activity levels of human XOR are present in the intestine [50,51] and liver [52–54], while a very low activity has been detected in other human organs [55,56].”
BackgroundOrgan distribution and molecular forms of human xanthine dehydrogenase/xanthine oxidase protein.
Sarnesto, A., Linder, N., & Raivio, K. O. (1996) · PubMed · Cited by 114 · see citing works
Confirmation of Superoxide Generation via Xanthine Oxidase in Streptozotocin-induced Diabetic Mice
Matsumoto, S., Koshiishi, I., Inoguchi, T., Nawata, H., & Utsumi, H. (2003) · Free Radical Research · doi:10.1080/1071576031000107344 · Cited by 112 · cited 1× · see citing works
“mice [179], and in fructose-induced hyperuricaemic mice [180].”
BackgroundFernández, L., Heredia, N., Grande, L., Gómez, G., Rimola, A., Marco, A. J., Gelpı́, E., Roselló‐Catafau, J., & Peralta, C. (2002) · Hepatology · doi:10.1053/jhep.2002.34616 · Cited by 112 · cited 1× · see citing works
“tion of xanthine and XOR to pre-conditioned rats [158].”
BackgroundZhang, Z., Blake, D. R., Stevens, C. R., Kanuler, J. M., Ward, P. G., Symons, M. C. R., Benboubetra, M., & Harrison, R. (1998) · Free Radical Research · doi:10.3109/10715769809065801 · Cited by 110 · cited 1× · see citing works
“The bactericidal activity of XOR may be potentiated either by the possibility to act as an NADH oxidase [29–31] or by the ability to produce peroxynitrite [32].”
BackgroundPeralta, C., Bulbena, O., Xaus, C., Prats, N., Cutrìn, J. C., Poli, G., Gelpı́, E., & Roselló‐Catafau, J. (2002) · Transplantation · doi:10.1097/00007890-200204270-00004 · Cited by 110 · cited 2× · see citing works
“elevation after artery ligation in cats [181], rabbits [182–186], and rats [27,157,187,188] as well as after haemorrhagic shock in mice [26] and”
BackgroundRole of oxygen free radicals in shock, ischemia, and organ preservation
Bingham, H. G. (1984) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-198408000-00086 · Cited by 109 · see citing works
Hassoun, P. M., Yu, F., Côté, C., Zulueta, J. J., Sawhney, R., Skinner, K. A., Skinner, H. B., Parks, D. A., & Lanzillo, J. J. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.158.1.9709116 · Cited by 108 · see citing works
Chen, L., Lan, Z., Lin, Q., Mi, X., He, Y., Wei, L., Lin, Y., Zhang, Y., & Deng, X. (2012) · Food and Chemical Toxicology · doi:10.1016/j.fct.2012.10.037 · Cited by 106 · cited 2× · see citing works
“XOR activity inhibition with polydatin reduced enzyme activity in serum and renal injury by attenuating hyperuricaemia and related inflammatory responses in fructose-induced urate nephropathic mice [180].”
BackgroundMitropoulos, D., Deliconstantinos, G., Zervas, A., Villiotou, V., Dimopoulos, C., & Stavrides, J. C. (1996) · The Journal of Urology · doi:10.1016/s0022-5347(01)65403-x · Cited by 105 · cited 1× · see citing works
“due to reduced blood flow in the dilated varicocele vein [219].”
BackgroundEffects of Oxidative Stress on Immunosuppression Induced by Selenium Deficiency in Chickens
Zhang, Z., Wang, Q., Zhang, J., Li, S., Wang, X., & Xu, S. (2012) · Biological Trace Element Research · doi:10.1007/s12011-012-9439-0 · Cited by 103 · cited 1× · see citing works
“In contrast, a lack of vitamin E, selenium or folic acid or a lipid-enriched diet increased liver XOR mRNA and protein expression [81,82].”
BackgroundBrass, C. A., Narciso, J. P., & Gollan, J. L. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115013 · Cited by 101 · see citing works
Weinbroum, A. A., Nielsen, V. G., Tan, S., Gelman, S., Matalon, S., Skinner, K. A., Bradley, E. L., & Parks, D. A. (1995) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1995.268.6.g988 · Cited by 101 · cited 2× · see citing works
“leased from the liver after ischaemia/reperfusion, in which XOR activity decreased in hepatic tissue and increased in the effluent perfusate [193].”
BackgroundIntestinal mucosal alterations in experimental cirrhosis in the rat: Role of oxygen free radicals
Ramachandran, A., Ramamoorthy, P., Thomas, S., Reddy, J. B., Pulimood, A. B., & Balasubramanian, K. A. (2002) · Hepatology · doi:10.1053/jhep.2002.31656 · Cited by 100 · cited 1× · see citing works
“cirrhotic rats [136]; and in rat brain following in vivo acute ammonia intoxication [137].”
BackgroundBaldus, S. E., Köster, R., Chumley, P. H., Heitzer, T. A., Rudolph, V., Ostad, M. A., Warnholtz, A., Staude, H.-J., Thuneke, F., Koss, K., et al. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.06.004 · Cited by 100 · cited 1× · see citing works
“artery disease [260].”
Page, S., POWELL, D., Benboubetra, M., Stevens, C. R., Blake, D. R., Selase, F., Wolstenholme, A. J., & Harrison, R. (1998) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(98)00028-2 · Cited by 98 · see citing works
Xanthine oxidoreductase in respiratory and cardiovascular disorders
Boueiz, A. R., Damarla, M., & Hassoun, P. M. (2008) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00007.2008 · Cited by 98 · cited 2× · see citing works
“Therefore, it is not simple to identify the specific role of these two enzymes in cardiovascular diseases (reviewed in [292]).”
BackgroundSerum uric acid and the risk of hypertension and chronic kidney disease
Feig, D. I. (2014) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000033 · Cited by 97 · cited 1× · see citing works
“by XOR inhibition is not yet demonstrated, although hyperuricaemia has been suggested to cause these pathologies through the downregulation of NO production (reviewed in [300]).”
BackgroundTourniquet-induced Exsanguination in Patients Requiring Lower Limb Surgery
Mathru, M., Dries, D. J., Barnes, L., Tonino, P. M., Sukhani, R., & Rooney, M. W. (1996) · Anesthesiology · doi:10.1097/00000542-199601000-00003 · Cited by 97 · see citing works
The Reaction of Reduced Xanthine Dehydrogenase with Molecular Oxygen
Harris, C. M., & Massey, V. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.13.8370 · Cited by 96 · see citing works
Plasma xanthine oxidase activity in patients with adult respiratory distress syndrome
Grum, C. M., Ragsdale, R. A., Ketai, L. H., & Simon, R. H. (1987) · Journal of Critical Care · doi:10.1016/0883-9441(87)90116-x · Cited by 94 · cited 1× · see citing works
“in the plasma of hypoxic subjects, such as patients with adult respiratory distress syndrome [217] and preterm newborn babies [218].”
BackgroundOxidation of circulating proteins in alcoholics: role of acetaldehyde and xanthine oxidase
Grattagliano, I., Vendemiale, G., Sabbà, C., Buonamico, P., & Altomare, E. (1996) · Journal of Hepatology · doi:10.1016/s0168-8278(96)80324-2 · Cited by 93 · cited 2× · see citing works
“[200,211,212], and viral infection [61,62,163,200–203].”
BackgroundGut Ischemia Mediates Lung Injury by a Xanthine Oxidase-Dependent Neutrophil Mechanism
Koike, K., Moore, F. A., Moore, E. E., Read, R. A., Carl, V. S., & Banerjee, A. N. (1993) · Journal of Surgical Research · doi:10.1006/jsre.1993.1072 · Cited by 91 · cited 1× · see citing works
“molybdenum-depleted diet abolished these alterations, suggesting a XOR-dependent neutrophil mechanism in the pathogenesis of remote organ injury [236].”
BackgroundNeutrophil Depletion Attenuates Human Intestinal Reperfusion Injury
Sisley, A. C., Desai, T. R., Harig, J. M., & Gewertz, B. L. (1994) · Journal of Surgical Research · doi:10.1006/jsre.1994.1130 · Cited by 91 · cited 1× · see citing works
“However, the contribution of leukocyte-derived ROS to the pathogenesis of ischaemia/reperfusion damage in vivo was confirmed by the observation that neutrophil depletion attenuates human intestinal reperfusion injury [195].”
BackgroundMuir, S. W., Harrow, C., Dawson, J., Lees, K. R., Weir, C. J., Sattar, N. A., & Walters, M. R. (2008) · Stroke · doi:10.1161/strokeaha.108.519793 · Cited by 90 · see citing works
Mellin, V., Isabelle, M., Oudot, A., Vergely, C., Monteil, C., Meglio, B. D., Henry, J., Dautréaux, B., Rochette, L., Thuillez, C., et al. (2005) · European Heart Journal · doi:10.1093/eurheartj/ehi305 · Cited by 90 · cited 1× · see citing works
“established chronic heart failure [254].”
Wright, R. M., Vaitaitis, G. M., Wilson, C., Repine, T. B., Terada, L. S., & Repine, J. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.22.10690 · Cited by 89 · see citing works
Miesel, R., & Zuber, M. A. (1993) · Inflammation · doi:10.1007/bf00914193 · Cited by 87 · cited 1× · see citing works
“Elevated XOR levels in human serumwere found in patients with acute and chronic viral hepatitis [61,62,163,200–203], infectious mononucleosis [200], rheumatic and autoimmune diseases [204], pneumonia [205], irritable bowel syndrome [206], schizophrenia [207], and type 2 diabetes [208,209].”
BackgroundKooij, A., Schiller, H. J., Schijns, M., Noorden, C. J. F. V., & Frederiks, W. M. (1994) · Hepatology · doi:10.1002/hep.1840190626 · Cited by 87 · cited 1× · see citing works
“After being released into plasma, XOR is rapidly converted to the XO form [124,227,232].”
BackgroundYiğiner, Ö., Özçelik, F., İnanç, T., Aparcı, M., Özmen, N., Cingözbay, B. Y., Kardeşoğlu, E., Süleymanoğlu, S., Şener, G., & Cebeci, B. S. (2007) · Clinical Research in Cardiology · doi:10.1007/s00392-007-0636-3 · Cited by 86 · cited 1× · see citing works
“In patients with metabolic syndrome and in patients with or at risk of cardiovascular disease, XOR inhibition by means of allopurinol treatment (1) had beneficial effects on endothelial function, thus improving brachial artery flow-mediated dilation and (2) reduced oxidative stress by decreasing myeloperoxidase levels…”
BackgroundSchröder, K., Vecchione, C., Jung, O., Schreiber, J. G., Shiri‐Sverdlov, R., van Gorp, P. J., Busse, R., & Brandes, R. P. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.03.026 · Cited by 86 · see citing works
Leukocyte-Endothelial Cell Adhesive Interactions: Role of Xanthine Oxidase-Derived Oxidants
Suzuki, M., Grisham, M. B., & Granger, D. N. (1991) · Journal of Leukocyte Biology · doi:10.1002/jlb.50.5.488 · Cited by 85 · cited 1× · see citing works
“Indeed, these oxidantsmay play a role in the cytotoxic activity of phagocytes either directly [22] by activating a chemotactic factor [23] and pro-collagenase [24], by increasing the adhesion of leukocytes [25] and cytokine production by monocytes [26], or by inducing the accumulation of leukocytes inmicrovasculature…”
BackgroundA re-evaluation of the tissue distribution and physiology of xanthine oxidoreductase
Kooij, A. (1994) · The Histochemical Journal · doi:10.1007/bf00174006 · Cited by 84 · cited 1× · see citing works
“(reviewed in [3]) until almost half a century ago, when mammalian XOR was shown to be a dehydrogenase in its native state [40,41].”
BackgroundAthar, M., Elmets, C. A., Bickers, D. R., & Mukhtar, H. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113993 · Cited by 84 · cited 1× · see citing works
“The increase of ROS-producing enzyme forms has been reported in burn injury [121]; haematoporphyrin derivative-mediated cutaneous photosensitisation [122]; in vivo and in vitro ethanol intoxication [119,123,124]; glutathione depletion [125]; endothelial”
BackgroundXu, X. Y., Hu, X., Lu, Z., Zhang, P., Zhao, L., Wessale, J. L., Bache, R. J., & Chen, Y. (2008) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2008.06.006 · Cited by 81 · cited 1× · see citing works
“induced left ventricular hypertrophy and dysfunction in mice [298].”
BackgroundIs Ischemic Preconditioning a Useful Strategy in Steatotic Liver Transplantation?
Fernández, L., Carrasco-Chaumel, E., Serafin, A. M., Xaus, C., Grande, L., Rimola, A., Roselló‐Catafau, J., & Peralta, C. (2004) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2004.00447.x · Cited by 80 · see citing works
Regulation of xanthine dehydrogenase and xanthine oxidase activity by hypoxia
Poss, W. B., Huecksteadt, T. P., Panus, P. C., Freeman, B. A., & Hoidal, J. R. (1996) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1996.270.6.l941 · Cited by 79 · cited 1× · see citing works
“Accordingly, the increased XOR activity observed in response to hypoxia or hypoxia and reoxygenation is due to the post-translational modulation of XOR in cultured bovine aortic endothelial cells [112].”
BackgroundKurosaki, M., Calzi, M. L., Scanziani, E., Garattini, E., & Terao, M. (1995) · Biochemical Journal · doi:10.1042/bj3060225 · Cited by 79 · cited 1× · see citing works
“, liver and intestine inmice [44] and humans [45].”
BackgroundSchmidt, A., Böhmer, A. E., Antunes, C., Schallenberger, C., Porciúncula, L., Elisabetsky, E., Lara, D., & Souza, D. O. (2008) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2008.00025.x · Cited by 78 · cited 1× · see citing works
“This is an open access article under anti-nociceptive effect of theXOR inhibitor allopurinol inmice [6].”
BackgroundEnhanced xanthine oxidase activity in mice treated with interferon and interferon inducers
Ghezzi, P., Bianchi, M., Mantovani, A., Spreafico, F., & Salmona, M. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(84)91630-9 · Cited by 78 · cited 2× · see citing works
“The administration of IFN or IFN-inducers to mice stimulated a marked increase of XOR activity in different organs [90], particularly”
BackgroundSimultaneous Liver and Lung Injury Following Gut Ischemia is Mediated by Xanthine Oxidase
Poggetti, R. S., Moore, F. A., Moore, E. E., KOEIKE, K., & Banerjee, A. M. (1992) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/00005373-199206000-00008 · Cited by 77 · cited 1× · see citing works
“depleted diet [235].”
Superoxide radical involvement in the pathogenesis of burn shock.
Sáez, J. C., Ward, P. H., Günther, B., & Vivaldi, E. (1984) · PubMed · Cited by 77 · see citing works
Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.
Mateos, F., Puig, J. G., Jiménez, M. L., & Fox, I. H. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112893 · Cited by 76 · see citing works
Circulating Xanthine Oxidase in Human Ischemia Reperfusion
Tan, S., Gelman, S., Wheat, J. K., & Parks, D. A. (1995) · Southern Medical Journal · doi:10.1097/00007611-199504000-00021 · Cited by 76 · cited 2× · see citing works
“reperfusion injury during an aortic cross-clamp procedure, and it was proposed that XOR-induced ROS may explain the damage to the lung or heart observed after ischaemia in human liver and intestine [223].”
BackgroundPurification and partial characterization of xanthine oxidase from human milk
Abadeh, S., Killacky, J., Benboubetra, M., & Harrison, R. (1992) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(92)90157-p · Cited by 75 · cited 4× · see citing works
“XOR can be found in human milk, although with a lower activity compared with cow milk [57,58].”
BackgroundInfluentialXanthine oxidoreductase activity in human liver disease
Stirpe, F., Ravaioli, M., Battelli, M. G., Musiani, S., & Grazi, G. L. (2002) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2002.05925.x · Cited by 74 · cited 1× · see citing works
“viral infections, including lung [95], brain [96], and liver [97] in mouse pathology and liver in human pathology [54].”
BackgroundSelf-citationNeogi, T., Casella, G., Rekhraj, S., Struthers, A. D., Choi, H. K., & Terkeltaub, R. A. (2011) · Arthritis & Rheumatism · doi:10.1002/art.33369 · Cited by 73 · cited 1× · see citing works
“infarction, and cardiovascular death (reviewed in [273,274]).”
Hypoxia Regulates Xanthine Dehydrogenase Activity at Pre- and Posttranslational Levels
Terada, L. S., Piermattei, D., Shibao, G. N., McManaman, J. L., & Wright, R. M. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1997.0367 · Cited by 73 · cited 1× · see citing works
“The effect of hypoxia in Swiss 3T3 cells has been reported to increase XOR activity without an increase of mRNA levels and followed by an increase ofmRNA levels andXOR activity [106].”
BackgroundThe Role of Urate and Xanthine Oxidase Inhibitors in Cardiovascular Disease
Casella, G., & Struthers, A. D. (2008) · Cardiovascular Drug Reviews · doi:10.1111/j.1527-3466.2007.00029.x · Cited by 72 · cited 1× · see citing works
“Moreover, allopurinol treatment resulted in blood pressure reduction in adolescents with newly diagnosed hypertension [288], although it is not clear if the benefit was due to XOR activity inhibition, uricaemia reduction, or the ROS scavenging activity of allopurinol (reviewed in [289]).”
BackgroundAmado, L. C., SALIARIS, A. P., Raju, S., Lehrke, S., John, M. S., XIE, J., Stewart, G. C., Fitton, T. P., Minhas, K. M., & BRAWN, J. (2005) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2005.04.008 · Cited by 71 · cited 1× · see citing works
“lopurinolwas able to prevent increases in systemic vasoconstriction and was able to improve myocardial contractility [253].”
BackgroundMilk xanthine oxidoreductase: the first one hundred years
Massey, V., & Harris, C. M. (1997) · Biochemical Society Transactions · doi:10.1042/bst0250750 · Cited by 71 · cited 1× · see citing works
“XOR has been known since the end of the 1800s and has been the object of a large number of studies, mainly because of its stability and high concentration in a widely available source, bovine milk (for historical reviews, see [2–4]).”
BackgroundA new route to peroxynitrite: a role for xanthine oxidoreductase
GODBER, B. L. J., Doel, J. J., Durgan, J., Eisenthal, R., & Harrison, R. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01639-2 · Cited by 71 · cited 1× · see citing works
“The bactericidal activity of XOR may be potentiated either by the possibility to act as an NADH oxidase [29–31] or by the ability to produce peroxynitrite [32].”
BackgroundDeliconstantinos, G., Villiotou, V., & Stavrides, J. C. (1996) · Biochemical Pharmacology · doi:10.1016/0006-2952(96)00110-4 · Cited by 69 · see citing works
Xanthine oxidase inhibitors improve energetics and function after infarction in failing mouse hearts
Naumova, A. V., Chacko, V. P., Ouwerkerk, R., Stull, L. B., Marbán, E., & Weiss, R. G. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00831.2005 · Cited by 68 · see citing works
Peroxisomes and reactive oxygen species, a lasting challenge
Angermüller, S., Islinger, M., & Völkl, A. (2009) · Histochemistry and Cell Biology · doi:10.1007/s00418-009-0563-7 · Cited by 68 · see citing works
Gürel, A. (2013) · Medical Science Monitor · doi:10.12659/msm.889068 · Cited by 68 · cited 1× · see citing works
“Elevated XOR levels in human serumwere found in patients with acute and chronic viral hepatitis [61,62,163,200–203], infectious mononucleosis [200], rheumatic and autoimmune diseases [204], pneumonia [205], irritable bowel syndrome [206], schizophrenia [207], and type 2 diabetes [208,209].”
BackgroundLung Injury After Hepatoenteric Ischemia-Reperfusion: Role of Xanthine Oxidase
Nielsen, V. G., Tan, S., Weinbroum, A., McCammon, A. T., Samuelson, P. N., Gelman, S., & Parks, D. A. (1996) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.154.5.8912749 · Cited by 67 · cited 1× · see citing works
“, with liver injury and elevated circulating XOR activity [184,237].”
BackgroundKuppusamy, U. R., Indran, M., & Rokiah, P. (2005) · Diabetic Medicine · doi:10.1111/j.1464-5491.2005.01630.x · Cited by 66 · cited 1× · see citing works
“Elevated XOR levels in human serumwere found in patients with acute and chronic viral hepatitis [61,62,163,200–203], infectious mononucleosis [200], rheumatic and autoimmune diseases [204], pneumonia [205], irritable bowel syndrome [206], schizophrenia [207], and type 2 diabetes [208,209].”
BackgroundXanthine oxidase activity in the dexamethasone-induced hypertensive rat
Wallwork, C. J., Parks, D. A., & Schmid‐Schönbein, G. W. (2003) · Microvascular Research · doi:10.1016/s0026-2862(03)00019-0 · Cited by 65 · cited 1× · see citing works
“gene expression, whichmay be regulated by nutritional factors, oxygen tension, steroid hormones [73], phorbol esters [74], regenerative”
BackgroundMononuclear Phagocyte Xanthine Oxidoreductase Contributes to Cytokine-Induced Acute Lung Injury
Wright, R. M., Ginger, L. A., Kosila, N., Elkins, N. D., Essary, B., McManaman, J. L., & Repine, J. E. (2003) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2003-0309oc · Cited by 65 · cited 2× · see citing works
“cells and the production of ROS, peroxynitrites, and cytokines [247,248].”
BackgroundUpregulation of xanthine oxidase by tobacco smoke condensate in pulmonary endothelial cells
Kayyali, U. S., Budhiraja, R., Pennella, C. M., Cooray, S., Lanzillo, J. J., Chalkley, R. G., & Hassoun, P. M. (2003) · Toxicology and Applied Pharmacology · doi:10.1016/s0041-008x(02)00076-5 · Cited by 65 · cited 1× · see citing works
“Additionally, tobacco smoke condensate up-regulated XOR activity in pulmonary endothelial cells by increasing XOR mRNA expression and XOR gene promoter activity [79].”
BackgroundSerum Xanthine Oxidase in Human Liver Disease
Battelli, M. G., Musiani, S., Valgimigli, M., Gramantieri, L., Tomassoni, F., Bolondi, L., & Stirpe, F. (2001) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2001.03700.x · Cited by 65 · cited 1× · see citing works
“Among human hepatopathies that induce increased plasma XOR levels, we can count massive toxic necrosis [200] as well as the liver damage due to halothane anaesthesia [211], alcoholism [212], or cholestatic disorders [203].”
BackgroundSelf-citationA re-evaluation of the tissue distribution and physiology of xanthine oxidoreductase
Kooij, A. (1994) · The Histochemical Journal · doi:10.1007/bf02388567 · Cited by 64 · see citing works
On the anaerobic and aerobic oxidation of xanthin and hypoxanthin by tissues and by milk
Morgan, E. J., Stewart, C. P., & Hopkins, F. G. (1922) · Proceedings of the Royal Society of London Series B Containing Papers of a Biological Character · doi:10.1098/rspb.1922.0047 · Cited by 64 · cited 1× · see citing works
“of hypoxanthine to xanthine and the latter to uric acid as the terminal steps of purine degradation in the highest primates [1].”
BackgroundWang, G., Qian, P., Jackson, F. R., Qian, G., & Wu, G. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.08.008 · Cited by 62 · see citing works
Repressed Expression of the Human Xanthine Oxidoreductase Gene
Xu, P., LaVallee, P., & Hoidal, J. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.8.5918 · Cited by 62 · see citing works
Circulating xanthine oxidase and neutrophil activation during human liver transplantation
Pesonen, E., Linder, N., Raivio, K. O., Sarnesto, A., Lapatto, R., Höckerstedt, K., Mäkisalo, H., & Andersson, S. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70321-x · Cited by 61 · cited 1× · see citing works
“Elevated plasma concentrations of XOR were observed during reperfusion after liver transplantation compared with preoperative levels [226].”
BackgroundPence, B. C., & Reiners, J. J. (1987) · PubMed · Cited by 61 · see citing works
Sulfhydryl oxidase-catalyzed conversion of xanthine dehydrogenase to xanthine oxidase
Clare, D. A., Blakistone, B. A., Swaisgood, H. E., & Horton, H. R. (1981) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(81)90427-6 · Cited by 61 · see citing works
Properties of the xanthine oxidase from human liver
Corte, E. D., Gozzetti, G., Novello, F., & Stirpe, F. (1969) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(69)90327-1 · Cited by 60 · cited 1× · see citing works
“Based on its levels of mRNA and protein expression, the highest activity levels of human XOR are present in the intestine [50,51] and liver [52–54], while a very low activity has been detected in other human organs [55,56].”
BackgroundUse of Melatonin to Prevent Selenite-Induced Cataract Formation in Rat Eyes
Yağcı, R., Aydın, B., Erdurmuş, M., Karadağ, R., Gürel, A., Durmuş, M., & Yiğitoğlu, R. (2006) · Current Eye Research · doi:10.1080/02713680600899663 · Cited by 60 · cited 1× · see citing works
“role of XOR-produced ROS in this model of eye damage [169].”
BackgroundReiners, J. J., Pence, B. C., Barcus, M. C. S., & Cantú, A. R. (1987) · PubMed · Cited by 59 · see citing works
Xanthine Oxidoreductase Gene Expression and Enzyme Activity in Developing Human Tissues
Saksela, M., Lapatto, R., & Raivio, K. O. (1998) · Neonatology · doi:10.1159/000014034 · Cited by 59 · cited 1× · see citing works
“, liver and intestine inmice [44] and humans [45].”
BackgroundIntermediate dehydrogenase-oxidase form of xanthine oxidoreductase in rat liver
Kamiński, Z., & Jeżewska, M. (1979) · Biochemical Journal · doi:10.1042/bj1810177 · Cited by 59 · cited 16× · see citing works
“The main molecular sources of such oxidants in endothelial cells have been identified in NAD(P)H oxidase, xanthine oxidase, and NO synthase, which are involved in the dysregulation of the vascular redox environment that is associated with impaired vascular function and cardiovascular diseases (reviewed in [290]).”
BackgroundInfluentialThe regulation of rat‐liver xanthine oxidase: Activation by proteolytic enzymes
Corte, E. D., & Stirpe, F. (1968) · FEBS Letters · doi:10.1016/0014-5793(68)80107-3 · Cited by 57 · cited 2× · see citing works
“(reviewed in [3]) until almost half a century ago, when mammalian XOR was shown to be a dehydrogenase in its native state [40,41].”
BackgroundNewaz, M., Yousefipour, Z., & Oyekan, A. (2006) · Journal of Cardiovascular Pharmacology · doi:10.1097/01.fjc.0000245402.62864.0a · Cited by 57 · cited 1× · see citing works
“In aging rats, the increased ROS-associated elevation of systolic blood pressure appeared to be dependent on vascular XOR but not on NAD(P)H oxidase activity [291].”
BackgroundAluminium increases xanthine oxidase activity and disturbs antioxidant status in the rat
Moumen, R., Aít-Oukhatar, N., Bureau, F., Fleury, C., Bouglé, D. L., Arhan, P., Neuville, D., & Viader, F. (2001) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/s0946-672x(01)80049-3 · Cited by 57 · cited 1× · see citing works
“Hepatic damage caused by a variety of toxic agents was associated with elevated serum XOR levels, particularly after treatment with CCl4 or thioacetamide in sheep [161] and after treatment with CCl4 [162, 163], colchicine [164], halothane [165], ethanol [166], saporin [130] or aluminium [167] in rats.”
BackgroundMODIFICATION OF OXIDATIVE STRESS IN RESPONSE TO INTESTINAL PRECONDITIONING1
Solà, A., Hotter, G., Prats, N., Xaus, C., Gelpı́, E., & Roselló‐Catafau, J. (2000) · Transplantation · doi:10.1097/00007890-200003150-00016 · Cited by 57 · cited 1× · see citing works
“to pre-conditioning procedures [152].”
Sabán-Ruiz, J., Alonso-Pacho, A., Fabregate, M., & Gonzalez-Quevedo, C. D. L. P. (2013) · Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry · doi:10.2174/1871523011312010011 · Cited by 56 · see citing works
Karabulut, A. B., Kafkaslı, A., Burak, F., & Gözükara, E. M. (2004) · Cell Biochemistry and Function · doi:10.1002/cbf.1152 · Cited by 56 · see citing works
Determination of human plasma xanthine oxidase activity by high-performance liquid chromatography
Yamamoto, T., Moriwaki, Y., Takahashi, S., Tsutsumi, Z., Yamakita, J.-I., Nasako, Y., Hiroishi, K., & Higashino, K. (1996) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/0378-4347(96)00071-0 · Cited by 55 · cited 1× · see citing works
“The detection of XOR in tissues and fluids containing low levels of XOR requires particularly sensitive assays, such as radiometry [59,60], fluorometry [61,62], HPLC [63], enzyme immunoassays, and immunohistochemistry [64–66].”
MethodNicholas, S. A., Bubnov, V. V., Yasinska, I. M., & Sumbayev, V. V. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0450-3 · Cited by 55 · see citing works
Kögler, H. (2003) · Cardiovascular Research · doi:10.1016/s0008-6363(03)00512-1 · Cited by 53 · cited 1× · see citing works
“XOR activity level, which was more pronounced in failing rat myocardium [255].”
BackgroundRole of oxygen radicals in tourniquet-related ischemia-reperfusion injury of human patients
Friedl, H. P., Till, G. O., Trentz, O., & Ward, P. A. (1991) · Journal of Molecular Medicine · doi:10.1007/bf01645168 · Cited by 53 · see citing works
Uric Acid, Heart Failure Survival, and the Impact of Xanthine Oxidase Inhibition
Harzand, A., Tamariz, L. J., & Hare, J. M. (2011) · Congestive Heart Failure · doi:10.1111/j.1751-7133.2011.00262.x · Cited by 53 · see citing works
Allopurinol Treatment Reduces Arterial Wave Reflection in Stroke Survivors
Khan, F., Casella, G., Wong, K., McSwiggan, S., Struthers, A. D., & Belch, J. J. F. (2008) · Cardiovascular Therapeutics · doi:10.1111/j.1755-5922.2008.00057.x · Cited by 52 · cited 1× · see citing works
“arterial wave reflection as a measure of vascular function [262].”
BackgroundLiver xanthine dehydrogenase and iron mobilization
Topham, R. W., Walker, M. C., & Calisch, M. P. (1982) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(82)91910-6 · Cited by 52 · cited 1× · see citing works
“In addition to cytotoxicity and tissue damage, XOR-generated ROS are responsible for many biological activities, including iron mobilisation from ferritin in the liver [17], iron absorption in the intestinal mucosal [18], and the induction of proliferation [19–21] as”
BackgroundSultatos, L. G. (1988) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22210-8 · Cited by 52 · cited 1× · see citing works
“The increase of ROS-producing enzyme forms has been reported in burn injury [121]; haematoporphyrin derivative-mediated cutaneous photosensitisation [122]; in vivo and in vitro ethanol intoxication [119,123,124]; glutathione depletion [125]; endothelial”
BackgroundGastric intramucosal pH and multiple organ injury
Nielsen, V. G., Tan, S., Baird, M. S., McCammon, A. T., & Parks, D. A. (1996) · Critical Care Medicine · doi:10.1097/00003246-199608000-00012 · Cited by 51 · cited 1× · see citing works
“protective towards the decrease of gastric intramucosal pH induced by hepatoenteric ischaemia/reperfusion, which is considered a marker of multiple organ injury [185].”
BackgroundMüller, M. J., Vollmar, B., Friedl, H.-P., & Menger, M. D. (1996) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(96)00028-7 · Cited by 51 · see citing works
Segal, B. H., Sakamoto, N., Patel, M. B., Maemura, K., Klein, A. S., Holland, S. M., & Bulkley, G. B. (2000) · Infection and Immunity · doi:10.1128/iai.68.4.2374-2378.2000 · Cited by 50 · see citing works
Gibbings, S. L., Elkins, N. D., Fitzgerald, H., Tiao, J., Weyman, M. E., Shibao, G. N., Fini, M. A., & Wright, R. M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.150847 · Cited by 50 · see citing works
Kooij, A., Schijns, M., Frederiks, W. M., Noorden, C. J. F., & James, J. (1993) · Virchows Archiv B Cell Pathology Including Molecular Pathology · doi:10.1007/bf02899240 · Cited by 49 · cited 2× · see citing works
“as well as with intracellular organelles, such as peroxisomes [48] (reviewed in [49]).”
BackgroundMaia, L. B., Duarte, R. O., Freire, A. P., Moura, J. J. G., & Mira, L. (2007) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-007-0229-7 · Cited by 48 · cited 1× · see citing works
“The bactericidal activity of XOR may be potentiated either by the possibility to act as an NADH oxidase [29–31] or by the ability to produce peroxynitrite [32].”
BackgroundBattelli, M. G., Abbondanza, A., & Stirpe, F. (1992) · Chemico-Biological Interactions · doi:10.1016/0009-2797(92)90093-z · Cited by 47 · see citing works
Self-citationShafik, A. N. (2012) · Digestive Diseases and Sciences · doi:10.1007/s10620-012-2391-1 · Cited by 47 · cited 1× · see citing works
“mesenteric artery ligation in rats led to an elevation in XOR serum levels, and XOR activity inhibition with febuxostat reduced the degree of local intestinal injury and the consequent remote hepatic and lung impairment [239].”
Backgroundde GROOT, H., & Littauer, A. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)81080-5 · Cited by 46 · cited 1× · see citing works
“Furthermore, XOR was released from the severely injured cells before the XDH/XO conversion occurred [145].”
BackgroundXanthine oxidase mediates myocardial injury after hepatoenteric ischemia-reperfusion
Nielsen, V. G., Tan, S., Baird, M. S., Samuelson, P. N., McCammon, A. T., & Parks, D. A. (1997) · Critical Care Medicine · doi:10.1097/00003246-199706000-00023 · Cited by 46 · see citing works
Cloning and expression in vitro of human xanthine dehydrogenase/oxidase
Saksela, M., & Raivio, K. O. (1996) · Biochemical Journal · doi:10.1042/bj3150235 · Cited by 46 · cited 1× · see citing works
“in vitro [68–70].”
Xanthine oxidoreductase release after descending thoracic aorta occlusion and reperfusion in rabbits
Nielsen, V. G., Weinbroum, A., Tan, S., Samuelson, P. N., Gelman, S., & Parks, D. A. (1994) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/s0022-5223(94)70041-9 · Cited by 45 · cited 1× · see citing works
“elevation after artery ligation in cats [181], rabbits [182–186], and rats [27,157,187,188] as well as after haemorrhagic shock in mice [26] and”
BackgroundLung injury and complement activation: Role of neutrophils and xanthine oxidase
Till, G. O., Friedl, H. P., & Ward, P. A. (1991) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(91)90046-6 · Cited by 45 · cited 1× · see citing works
“increase of XOR activity in plasma,whichwas partially related to the appearance of histamine in plasma [168].”
Background
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Research works printed but not linked: 1
- R.C. Bray, Molybdenum iron-sulfur flavin hydroxylases and related en- zymes, in: P.D. Boyer (Ed.), The enzymes, 12, Academic Press, New York, 1975, pp. 299-419.
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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 · see citing works
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 1,511 · see citing works
“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 1,375 · see citing works
“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 · see citing works
“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 · see citing works
Uric acid and cardiovascular disease
Ndrepepa, G. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.05.046 · Cited by 503 · see citing works
Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases
Becker, B. F., Jacob, M., Leipert, S., Salmon, A. H. J., & Chappell, D. (2015) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12629 · Cited by 465 · see citing works
Xanthine oxidoreductase: One enzyme for multiple physiological tasks
Bortolotti, M., Polito, L., Battelli, M. G., & Bolognesi, A. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101882 · Cited by 405 · see citing works
“The conversion from XDH to XO physiologically occurs through oxidation of the sulfhydryl groups when the enzyme is released from the cell into gastrointestinal lumen and urinary tract, as well as in biological fluids, such as milk and serum [6].”
BackgroundInfluentialSelf-citationNew insights into purine metabolism in metabolic diseases: role of xanthine oxidoreductase activity
Furuhashi, M. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00378.2020 · Cited by 371 · see citing works
Oxidative Stress and Human Hypertension: Vascular Mechanisms, Biomarkers, and Novel Therapies
Montezano, A. C. I., Dulak-Lis, M. G., Tsiropoulou, S., Harvey, A., Briones, A. M., & Touyz, R. M. (2015) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2015.02.008 · Cited by 324 · see citing works
Xanthine Oxidoreductase‐Derived Reactive Species: Physiological and Pathological Effects
Battelli, M. G., Polito, L., Bortolotti, M., & Bolognesi, A. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3527579 · Cited by 314 · see citing works
“XOR activity is known to be upregulated in response to inflammatory cytokines [28], which induce the XDH to XO transition and also increase the XOR level in plasma [11], supporting the hypothesis that XOR is a component of the innate immune system (reviewed in [29]).”
BackgroundInfluentialSelf-citationBiochemical basis and metabolic interplay of redox regulation
Zhang, L., Wang, X., Cueto, R., Effi, C., Zhang, Y., Tan, H., Qin, X., Ji, Y., Yang, X., & Wang, H. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101284 · Cited by 308 · see citing works
“XOR as a source of ROS contributes to oxidative stress in a variety of disease, particularly IR injury [103].”
BackgroundHyperuricemia-Related Diseases and Xanthine Oxidoreductase (XOR) Inhibitors: An Overview
Chen, C., Lü, J.-M., & Yao, Q. C. (2016) · Medical Science Monitor · doi:10.12659/msm.899852 · Cited by 307 · see citing works
The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors
Liu, N., Xu, H., Sun, Q., Yu, X., Chen, W., Wei, H., Jiang, J., Xu, Y., & Lu, W. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/1470380 · Cited by 265 · see citing works
Uric acid in health and disease: From physiological functions to pathogenic mechanisms
Wen, S., Arakawa, H., & Tamai, I. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108615 · Cited by 246 · see citing works
Salehi, B., Azzini, E., Zucca, P., Varoni, E. M., Kumar, N. V. A., Dini, L., Panzarini, E., Rajković, J., Fokou, P. V. T., Peluso, I., et al. (2020) · Applied Sciences · doi:10.3390/app10030947 · Cited by 234 · see citing works
“metabolism of xanthine to uric acid and is a source of oxygen free radicals [26].”
BackgroundSelf-citationMarchev, A. S., Dimitrova, P. A., Burns, A. J., Kostov, R. V., Dinkova‐Kostova, A. T., & Georgiev, M. I. (2017) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13407 · Cited by 223 · see citing works
Origin and Consequences of Necroinflammation
Sarhan, M., Land, W. G., Tonnus, W., Hugo, C., & Linkermann, A. (2018) · Physiological Reviews · doi:10.1152/physrev.00041.2016 · Cited by 210 · see citing works
The role of xanthine oxidoreductase and uric acid in metabolic syndrome
Battelli, M. G., Bortolotti, M., Polito, L., & Bolognesi, A. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.05.003 · Cited by 210 · see citing works
Self-citationThe effects of oxidative stress on the development of atherosclerosis
Khosravi, M., Poursaleh, A., Ghasempour, G., Shaikhnia, F., & Najafi, M. (2018) · Biological Chemistry · doi:10.1515/hsz-2018-0397 · Cited by 195 · see citing works
Xanthine oxidoreductase in atherosclerosis pathogenesis: Not only oxidative stress
Battelli, M. G., Polito, L., & Bolognesi, A. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.10.006 · Cited by 179 · see citing works
Self-citationWilson, A. J., Gill, E. K., Abudalo, R. A., Edgar, K. S., Watson, C. J., & Grieve, D. (2017) · Heart · doi:10.1136/heartjnl-2017-311448 · Cited by 177 · see citing works
ROS signaling and redox biology in endothelial cells
Panieri, E., & Santoro, M. M. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1928-9 · Cited by 168 · see citing works
“Due to its high affinity for the glycosaminoglycans present on their cell surface, XO can bind to endothelial cells and promote vascular dysfunction [126] [127].”
BackgroundXanthine oxidoreductase in cancer: more than a differentiation marker
Battelli, M. G., Polito, L., Bortolotti, M., & Bolognesi, A. (2015) · Cancer Medicine · doi:10.1002/cam4.601 · Cited by 164 · see citing works
“Such conversion may occur in different pathologic circumstances, including tissue damage by physical agents, poisoning with endogenous or toxic substances, and various hypoxic/ischemic conditions (reviewed in [4]).”
BackgroundSelf-citationTransplantation and Damage-Associated Molecular Patterns (DAMPs)
Land, W. G., Agostinis, P., Gasser, S., Garg, A. D., & Linkermann, A. (2016) · American Journal of Transplantation · doi:10.1111/ajt.13963 · Cited by 166 · see citing works
Shortage of Cellular ATP as a Cause of Diseases and Strategies to Enhance ATP
Johnson, T. A., Jinnah, H. A., & Kamatani, N. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00098 · Cited by 148 · see citing works
Natural compounds with xanthine oxidase inhibitory activity: A review
Mehmood, A., Ishaq, M. S., Zhao, L., Safdar, B., Rehman, A., Munir, M., Raza, A., Nadeem, M., Iqbal, W., & Wang, C. (2018) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13437 · Cited by 143 · see citing works
Metabolic syndrome and cancer risk: The role of xanthine oxidoreductase
Battelli, M. G., Bortolotti, M., Polito, L., & Bolognesi, A. (2018) · Redox Biology · doi:10.1016/j.redox.2018.101070 · Cited by 127 · see citing works
“is not lost when competitive, such as allopurinol, or non-competitive XOR inhibitors, such as febuxostat, inactivate Moco site (reviewed in [6]).”
BackgroundSelf-citationThe association between metabolic syndrome components and the development of atherosclerosis
Aboonabi, A., Meyer, R. R., & Singh, I. (2019) · Journal of Human Hypertension · doi:10.1038/s41371-019-0273-0 · Cited by 121 · see citing works
“Experimental and clinical studies have proven that elevated UA levels exert deleterious effects on cardiovascular health, including increased OS [40, 41], reduced availability of nitric oxide and endothelial dysfunction [42–44], promotion of local and systemic inflammation [45, 46], vasoconstric-”
BackgroundXanthine Oxidoreductase in Drug Metabolism: Beyond a Role as a Detoxifying Enzyme
Battelli, M. G., Polito, L., Bortolotti, M., & Bolognesi, A. (2016) · Current Medicinal Chemistry · doi:10.2174/0929867323666160725091915 · Cited by 112 · see citing works
“However, an increase in XOR expression may be induced by hormones, growth factors, cytokines and low oxygen tension (reviewed in [7]).”
BackgroundInfluentialSelf-citationNrf2 and Heme Oxygenase-1 Involvement in Atherosclerosis Related Oxidative Stress
Alonso-Piñero, J. A., González-Rovira, A., Sánchez-Gomar, I., Moreno, J. A., & Durán-Ruiz, M. C. (2021) · Antioxidants · doi:10.3390/antiox10091463 · Cited by 110 · see citing works
“XO has been associated with different CVDs [48].”
BackgroundImpact of hyperuricemia on chronic kidney disease and atherosclerotic cardiovascular disease
Nishizawa, H., Maeda, N., & Shimomura, I. (2022) · Hypertension Research · doi:10.1038/s41440-021-00840-w · Cited by 112 · see citing works
Kumar, R., Joshi, G., Kler, H., Kalra, S., Kaur, M., & Arya, R. (2017) · Medicinal Research Reviews · doi:10.1002/med.21457 · Cited by 106 · see citing works
Marahatha, R., Basnet, S., Bhattarai, B. R., Budhathoki, P., Aryal, B., Adhikari, B., Lamichhane, G., Poudel, D. K., & Parajuli, N. (2021) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-020-03162-5 · Cited by 105 · see citing works
Free Radicals and Other Reactive Species in Disease
Halliwell, B. B. (2015) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0002269.pub3 · Cited by 102 · see citing works
Function of Uric Acid Transporters and Their Inhibitors in Hyperuricaemia
Sun, H., Wu, Y.-W., Bian, H., Yang, H., Wang, H., Meng, X., & Jin, J. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.667753 · Cited by 101 · see citing works
Reactive species-induced microvascular dysfunction in ischemia/reperfusion
Yu, H. H., Kalogeris, T., & Korthuis, R. J. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.02.031 · Cited by 97 · see citing works
Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration
Fasullo, M., & Endres, L. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16059431 · Cited by 96 · see citing works
“While ROS can directly damage DNA, they can also generate oxidized dNTPs, such as 8-oxo-dGTP, which can then be incorporated into either mitochondrial or genomic DNA, creating genetic instability [16,17].”
BackgroundFuruhashi, M., Matsumoto, M., Tanaka, M., Moniwa, N., Murase, T., Nakamura, T., Ohnishi, H., Saitoh, S., Shimamoto, K., & Miura, T. (2018) · Circulation Journal · doi:10.1253/circj.cj-18-0082 · Cited by 90 · see citing works
Xanthine oxidoreductase: A leading actor in cardiovascular disease drama
Polito, L., Bortolotti, M., Battelli, M. G., & Bolognesi, A. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102195 · Cited by 92 · see citing works
“last two steps of purine catabolism and has a rate-limiting function, which precludes the salvage pathway of purine nucleotides, as its products, xanthine and uric acid, are irreversible [6].”
BackgroundSelf-citationNakatsu, Y., Seno, Y., Kushiyama, A., Sakoda, H., Fujishiro, M., Katasako, A., Mori, K., Matsunaga, Y., Fukushima, T., Kanaoka, R., et al. (2015) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00443.2014 · Cited by 88 · see citing works
“Although UA is reportedly capable of acting as a prooxidant like other reducing substances such as ascorbic acid, the reaction catalyzed by XO converting xanthine to UA requires oxygen (1).”
BackgroundEndothelial dysfunction in neuroprogressive disorders—causes and suggested treatments
Morris, G., Puri, B. K., OLIVE, L. S., Carvalho, A. F., Berk, M., Walder, K. R., Gustad, L. T., & Maes, M. H. J. (2020) · BMC Medicine · doi:10.1186/s12916-020-01749-w · Cited by 83 · see citing works
“This is unsurprising given the fact that circulating activated XO is a major, if not the predominant, source of hydrogen peroxide and superoxide in patients displaying high levels of systemic inflammation and oxidative stress [183, 189, 190].”
BackgroundOtaki, Y., Watanabe, T., Kinoshita, D., Yokoyama, M., Takahashi, T., Toshima, T., Sugai, T., Murase, T., Nakamura, T., Nishiyama, S., et al. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.11.077 · Cited by 81 · see citing works
“Therefore, XOR is recognized as a significant source of ROS contributing the development of oxidative stress-related tissue injury [4].”
BackgroundRoy, B. (2025) · Medical Sciences · doi:10.3390/medsci13030087 · Cited by 89 · see citing works
Hyperuricemia: A key contributor to endothelial dysfunction in cardiovascular diseases
Wei, X., Zhang, M., Huang, S., Lan, X., Zheng, J. J., Luo, H., He, Y. Z., & Lei, W. (2023) · The FASEB Journal · doi:10.1096/fj.202300393r · Cited by 81 · see citing works
Xanthine oxidase-mediated oxidative stress promotes cancer cell-specific apoptosis
Xu, H., Li, C., Mozziconacci, O., Zhu, R., Xu, Y., Tang, Y., Chen, R., Huang, Y. L., Holzbeierlein, J. M., Schöneich, C., et al. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.05.019 · Cited by 77 · see citing works
“So far, multiple mechanisms have been reported in regulating XDH activity at the transcriptional and posttranscriptional levels [45].”
BackgroundThe Good, the Bad and the New about Uric Acid in Cancer
Allegrini, S., Garcia‐Gil, M., Pesi, R., Camici, M., & Tozzi, M. G. (2022) · Cancers · doi:10.3390/cancers14194959 · Cited by 74 · see citing works
Koju, N., Taleb, A., Zhou, J., Ge, L., Yang, J., Cao, X., Lei, H., & Ding, Q. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.11.128 · Cited by 71 · see citing works
Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection
Bahadoran, Z., Mirmiran, P., Kashfi, K., & Ghasemi, A. (2021) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-021-02606-2 · Cited by 68 · see citing works
Aroor, A. R., Jia, G., Habibi, J., Sun, Z., Ramirez‐Perez, F. I., Brady, B., Chen, D., Martinez‐Lemus, L. A., Manrique, C. M., Nistala, R., et al. (2017) · Metabolism · doi:10.1016/j.metabol.2017.06.006 · Cited by 61 · see citing works
“Although uric acid has been implicated in mediating glomerular injury in several preclinical studies, including ours in WD-fed male mice [6, 34], the role of XO activation in ECs has also been implicated in endothelial cortical stiffness through glycocalyx polymerization and shedding [35-37].”
Mechanisms impairing blood pressure responses to nitrite and nitrate
Oliveira‐Paula, G. H., Pinheiro, L. C., & Tanus-Santos, J. E. (2019) · Nitric Oxide · doi:10.1016/j.niox.2019.01.015 · Cited by 60 · see citing works
Differential regulation of hypoxanthine and xanthine by obesity in a general population
Furuhashi, M., Koyama, M., Higashiura, Y., Murase, T., Nakamura, T., Matsumoto, M., Sakai, A., Ohnishi, H., Tanaka, M., Saitoh, S., et al. (2020) · Journal of Diabetes Investigation · doi:10.1111/jdi.13207 · Cited by 60 · see citing works
The double faced role of xanthine oxidoreductase in cancer
Chen, M.-M., & Meng, L. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00800-7 · Cited by 59 · see citing works
Gao, J., Liu, X., Zhang, B., Mao, Q., Zhang, Z., Zou, Q., Dai, X., & Wang, S. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112077 · Cited by 57 · see citing works
Amodio, G., Moltedo, O., Faraonio, R., & Remondelli, P. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/4946289 · Cited by 56 · see citing works
Hyperuricemia and nonalcoholic fatty liver disease: from bedside to bench and back
Xu, C. (2015) · Hepatology International · doi:10.1007/s12072-015-9682-5 · Cited by 54 · see citing works
“XOR is the rate limiting enzyme in purine metabolism, catalyzing hydroxylation of hypoxanthine to xanthine and of xanthine to urate [7].”
BackgroundLarge‐Scale Metabolomics and the Incidence of Cardiovascular Disease
Lind, L., Fall, T., Ärnlöv, J., Elmståhl, S., & Sundström, J. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.122.026885 · Cited by 52 · see citing works
Surowiec, I., Ärlestig, L., Rantapää-Dahlqvist, S., & Trygg, J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0164196 · Cited by 53 · see citing works
Independent links between plasma xanthine oxidoreductase activity and levels of adipokines
Furuhashi, M., Matsumoto, M., Murase, T., Nakamura, T., Higashiura, Y., Koyama, M., Tanaka, M., Moniwa, N., Ohnishi, H., Saitoh, S., et al. (2018) · Journal of Diabetes Investigation · doi:10.1111/jdi.12982 · Cited by 49 · see citing works
The potential of stimulating nitric oxide formation in the treatment of hypertension
Pinheiro, L. C., Tanus-Santos, J. E., & de Castro, M. M. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1310840 · Cited by 49 · see citing works
The Reactive Species Interactome in the Brain
Malard, E., Valable, S., Bernaudin, M., Pérès, E., & Chatre, L. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8238 · Cited by 41 · see citing works
Loss of Xanthine Oxidoreductase Potentiates Propagation of Hepatocellular Carcinoma Stem Cells
Sun, Q., Zhang, Z., Lu, Y., Liu, Q., Xu, X., Xu, J., Liu, Y., Yu, H., Yu, D., & Sun, B. (2019) · Hepatology · doi:10.1002/hep.30978 · Cited by 46 · see citing works
“XOR, a housekeeping enzyme, is known as the rate-limiting enzyme in purine catabolism, and is predominantly expressed in the liver.(18) Multiple lines of evidence have determined that XOR functions as a multifunctional enzyme and is involved in various physiological and pathological responses, including cancer.”
BackgroundInfluentialChronic kidney disease: Which role for xanthine oxidoreductase activity and products?
Polito, L., Bortolotti, M., Battelli, M. G., & Bolognesi, A. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106407 · Cited by 45 · see citing works
Self-citationKusano, T., Ehirchiou, D., Matsumura, T., Chobaz, V., Nasi, S., Castelblanco, M., So, A. K.-L., Lavanchy, C., Acha‐Orbea, H., Nishino, T., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12565-z · Cited by 46 · see citing works
Nishino, T., Okamoto, K., Kawaguchi, Y., Matsumura, T., Eger, B. T., PAI, E. F., & Nishino, T. (2015) · FEBS Journal · doi:10.1111/febs.13277 · Cited by 44 · see citing works
Hackenhaar, F. S., Medeiros, T. M., Heemann, F. M., Behling, C. S., Putti, J. S., Mahl, C. D., Verona, C., da Silva, A. C. A., Guerra, M. C., Gonçalves, C. A., et al. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/8704352 · Cited by 43 · see citing works
Genetic Alterations in Oxidant and Anti-Oxidant Enzymes in the Vascular System
Awad, M. A., Aldosari, S., & Abid, M. R. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00107 · Cited by 42 · see citing works
Baicalein decreases uric acid and prevents hyperuricemic nephropathy in mice
Meng, X., Mao, Z., Li, X., Zhong, D., Li, M., Jia, Y., Wei, J., Yang, B., & Zhou, H. (2017) · Oncotarget · doi:10.18632/oncotarget.16928 · Cited by 42 · see citing works
“Besides, a wide range of activity levels were in biological fluids, such as blood [35].”
BackgroundThe Role of Xanthine Oxidase in Pregnancy Complications: A Systematic Review
Annesi, L., Tossetta, G., Borghi, C., & Piani, F. (2024) · Antioxidants · doi:10.3390/antiox13101234 · Cited by 41 · see citing works
“It has been shown that several changes observed in placental tissue during in vitro altered perfusion are similar to those reported in placentae from certain pregnancy pathologies, suggesting that H/R may be one of the underlying patho-physiological mechanisms of many obstetric conditions.”
ResultXanthine oxidoreductase and its inhibitors: relevance for gout
Day, R. O., Kamel, B., Kannangara, D. R. W., Williams, K. M., & Graham, G. G. (2016) · Clinical Science · doi:10.1042/cs20160010 · Cited by 41 · see citing works
Xie, Z., Luo, X., Zou, Z., Zhang, X., Huang, F., Li, R., Liao, S., & Liu, Y. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.01.053 · Cited by 41 · see citing works
Pleskačová, A., Brejcha, S., Pácal, L., Kaňková, K., & Tomandl, J. (2016) · Chromatographia · doi:10.1007/s10337-016-3208-8 · Cited by 40 · see citing works
Chen, G., Ye, T., Chen, H., Zhao, Z.-Y., Tang, W.-Q., Wang, L., & Xia, J.-L. (2017) · Oncogenesis · doi:10.1038/oncsis.2017.81 · Cited by 42 · see citing works
Oxidative Stress: Promoter of Allergic Sensitization to Protease Allergens?
van Rijt, L. S., Utsch, L., Lutter, R., & van Ree, R. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061112 · Cited by 40 · see citing works
“All NOX family members are transmembrane proteins that transport electrons across biological membranes to reduce oxygen to superoxide.”
BackgroundInfluentialPro-Aging Effects of Xanthine Oxidoreductase Products
Battelli, M. G., Bortolotti, M., Bolognesi, A., & Polito, L. (2020) · Antioxidants · doi:10.3390/antiox9090839 · Cited by 38 · see citing works
“Furthermore, the killing ability of XOR products has been exploited for the production of immunoconjugates with the purpose of eliminating undesired cells [35].”
BackgroundSelf-citationAndrés, C. M. C., de la Lastra, J. M. P., Andrés, C., Plou, F. J., & Pérez‐Lebeña, E. (2023) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.23455 · Cited by 40 · see citing works
Zhang, W. (2023) · Advances in clinical chemistry · doi:10.1016/bs.acc.2023.05.003 · Cited by 36 · see citing works
Xanthine Oxidase/Dehydrogenase Activity as a Source of Oxidative Stress in Prostate Cancer Tissue
Veljković, A., Hadži-Djokić, J., Sokolovic, D. T., Bašić, D., Veličković, L. J., Stojanović, M., Popović, D., & Kocic, G. M. (2020) · Diagnostics · doi:10.3390/diagnostics10090668 · Cited by 36 · see citing works
“Besides proteolytic and cysteine disulphide modifications, XDH/XO protein phosphorylation or even limited proteolysis were also reported previously [40].”
BackgroundThe Intestinal Redox System and Its Significance in Chemotherapy‐Induced Intestinal Mucositis
Yu, Q., Zhang, H., Guo, Y., Han, B., & Jiang, P. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/7255497 · Cited by 35 · see citing works
“In humans, XOR is primarily located in the liver and intestine [34], whereas other human organs display minute XOR activity (Figure 1) [35, 36].”
In silico design and synthesis of targeted rutin derivatives as xanthine oxidase inhibitors
Malik, N., Dhiman, P., & Khatkar, A. (2019) · BMC Chemistry · doi:10.1186/s13065-019-0585-8 · Cited by 35 · see citing works
Rendić, S., Crouch, R. D., & Guengerich, F. P. (2022) · Archives of Toxicology · doi:10.1007/s00204-022-03304-3 · Cited by 34 · see citing works
Mineral Micronutrients in Asthma
Zajac, D. (2021) · Nutrients · doi:10.3390/nu13114001 · Cited by 33 · see citing works
Nitrite-stimulated Gastric Formation of S-nitrosothiols As An Antihypertensive Therapeutic Strategy
Oliveira‐Paula, G. H., & Tanus-Santos, J. E. (2018) · Current Drug Targets · doi:10.2174/1389450119666180816120816 · Cited by 33 · see citing works
Greene, E., Cauble, R. N., Dhamad, A. E., Kidd, M. T., Kong, B. C., Howard, S. M., Castro, H. F., Campagna, S. R., Bedford, M. R., & Dridi, S. (2020) · Frontiers in Veterinary Science · doi:10.3389/fvets.2020.00458 · Cited by 33 · see citing works
“Because hypoxanthine is very low under physiological conditions, our data suggested that hypoxanthine was build up with the progression of WB myopathy with concomitant production of reactive oxygen species (75, 76).”
BackgroundTian, R., Peng, R., Yang, Z., Peng, Y., & Lu, N. (2020) · Nitric Oxide · doi:10.1016/j.niox.2020.01.007 · Cited by 32 · see citing works
Early diabetic kidney disease: Focus on the glycocalyx
Yu, H., Song, Y.-Y., & Li, X. (2023) · World Journal of Diabetes · doi:10.4239/wjd.v14.i5.460 · Cited by 32 · see citing works
Klisic, A. N., Kocic, G. M., Kavarić, N., Jovanović, M., Stanišić, V., & Ninić, A. (2017) · Clinical and Experimental Medicine · doi:10.1007/s10238-017-0483-0 · Cited by 32 · see citing works
“In addition, high level of uric acid stimulates vascular smooth muscle cells proliferation and migration [11], and induces them to produce MCP-1 [23], thus further aggravating endothelial dysfunction.”
BackgroundKawachi, Y., Fujishima, Y., Nishizawa, H., Nakamura, T., Akari, S., Murase, T., Saito, T., Miyazaki, Y., Nagao, H., Fukuda, S., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.144762 · Cited by 30 · see citing works
Hypoxanthine: a new paradigm to interpret the origin of transfusion toxicity.
Casali, E., Berni, P., Spisni, A., Baricchi, R., & Pertinhez, T. A. (2016) · Europe PMC (PubMed Central) · doi:10.2450/2015.0177-15 · Cited by 30 · see citing works
The Role of Uric Acid in the Acute Myocardial Infarction: A Narrative Review
Demiray, A., Afşar, B., Covic, A. C., Kuwabara, M., Ferro, C. J., Lanaspa, M. A., Johnson, R. J., & Kanbay, M. (2021) · Angiology · doi:10.1177/00033197211012546 · Cited by 31 · see citing works
“It has also been shown that XO and NADPH oxidase are closely related to ROS producers and that they can mutually activate each other.(36) Uric acid is likely to play a role in the progression of the atherosclerotic plaque in coronary arteries, by acting as a prooxidant that promotes lipoprotein oxidation; atherosclero…”
BackgroundNakatani, A., Nakatani, S., Ishimura, E., Murase, T., Nakamura, T., Sakura, M., Tateishi, Y., Tsuda, A., Kurajoh, M., Mori, K., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-15419-0 · Cited by 29 · see citing works
Xanthine oxidase is hyper-active in Duchenne muscular dystrophy
Lindsay, A., McCourt, P. M., Karachunski, P. I., Lowe, D. A., & Ervasti, J. M. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.10.404 · Cited by 30 · see citing works
“Evidence has shown that inflammatory and hypoxic conditions like that measured in DMD [14,44] can stimulate marked increases in XO mRNA and activity [45], thus potentially explaining the elevation in mdx mouse XO mRNA.”
Tamura, T., Sano, M., Matsuoka, T., Yoshizawa, J., Yamamoto, R., Katsumata, Y., Endo, J., Homma, K., Kajimura, M., Suzuki, M., et al. (2019) · Shock · doi:10.1097/shk.0000000000001459 · Cited by 29 · see citing works
“Xanthine oxidoreductase (XOR) is one of the major sources of ROS production after I/R injury (26, 27).”
BackgroundOxidation pathways underlying the pro-oxidant effects of apigenin
Andueza, A., García-Garzón, A., de Galarreta, M. R., Ansorena, E., Iraburu, M. J., López-Zabalza, M. J., & Martínez-Irujo, J. J. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.003 · Cited by 27 · see citing works
“In mammals, XO mRNA has been detected in most tissues, and the highest transcript levels are found in liver and intestine [38,55].”
BackgroundOliveira‐Paula, G. H., Pinheiro, L. C., Guimarães, D. A., Conde-Tella, S. O., Blanco, A. L. F., de Angelis, C. D., Schechter, A. N., & Tanus-Santos, J. E. (2016) · Redox Biology · doi:10.1016/j.redox.2016.04.001 · Cited by 27 · see citing works
“to uric acid in the metabolic pathway of purine degradation [1, 2].”
BackgroundKurajoh, M., Fukumoto, S., Emoto, M., Murase, T., Nakamura, T., Ishihara, T., Go, H., Yamamoto, K., Nakatani, S., Tsuda, A., et al. (2019) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2019-0199 · Cited by 27 · see citing works
Increased plasma xanthine oxidoreductase activity deteriorates coronary artery spasm
Watanabe, K., Shishido, T., Otaki, Y., Watanabe, T., Sugai, T., Toshima, T., Takahashi, T., Yokoyama, M., Kinoshita, D., Murase, T., et al. (2018) · Heart and Vessels · doi:10.1007/s00380-018-1207-4 · Cited by 26 · see citing works
“XOR pathways are one of the major ROS-generating systems in the vascular vessels.”
BackgroundInfluentialFuruhashi, M., Koyama, M., Matsumoto, M., Murase, T., Nakamura, T., Higashiura, Y., Tanaka, M., Moniwa, N., Ohnishi, H., Saitoh, S., et al. (2019) · Endocrine Journal · doi:10.1507/endocrj.ej19-0053 · Cited by 26 · see citing works
Otaki, Y., Watanabe, T., Konta, T., Watanabe, M., Asahi, K., Yamagata, K., Fujimoto, S., Tsuruya, K., Narita, I., Kasahara, M., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-71301-6 · Cited by 26 · see citing works
Pang, X., Tang, C., Guo, R., & Chen, X. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108020 · Cited by 26 · see citing works
- 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 › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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