Cited by 260Gout, Hyperuricemia, Uric AcidBiochemical and Molecular ResearchNitric Oxide and Endothelin Effects

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Pathophysiology of circulating xanthine oxidoreductase: New emerging roles for a multi-tasking enzyme

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Battelli, Maria Giulia, Bolognesi, Andrea, Polito, Letizia·2014·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

DOI 10.1016/j.bbadis.2014.05.022

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Abstract

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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Xanthine 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 192 · cited 1×
“(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-citation
Circulating 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×
“perfusate was similar to the paralleled decrease in endogenous tissue enzyme [192].”
Background
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
Mammalian peroxisomes and reactive oxygen species
Schrader, M., & Fahimi, H. D. (2004) · Histochemistry and Cell Biology · doi:10.1007/s00418-004-0673-1 · Cited by 175
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×
“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].”
Background
Cellular 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
Uric acid and xanthine oxidase: future therapeutic targets in the prevention of cardiovascular disease?
Dawson, J., & Walters, J. (2006) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2006.02785.x · Cited by 167 · cited 2×
“indicated that uric acid reductionmay contribute to the reduction of risk (reviewed in [277,278]).”
Background
Uric 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×
“infarction, and cardiovascular death (reviewed in [273,274]).”
Background
Xanthine Oxidase Inhibition For The Treatment Of Cardiovascular Disease: A Systematic Review and Meta‐Analysis
Higgins, 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
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×
“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]).”
Background
Impaired S-Nitrosylation of the Ryanodine Receptor Caused by Xanthine Oxidase Activity Contributes to Calcium Leak in Heart Failure
González, 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 160 · cited 2×
“cate that nitroso-redox disequilibrium at the sarcoplasmic reticulum level is due to oxidative stress, which is possibly dependent on XOR up-regulation [266].”
Background
Induction of nitric oxide synthesis and xanthine oxidase and their roles in the antimicrobial mechanism against Salmonella typhimurium infection in mice
Umezawa, 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×
“The inhibition of these enzyme activities resulted in the exacerbation of the infection, indicating their importance as anti-microbial leukocyte defences [98].”
Background
Mechanisms of conversion of xanthine dehydrogenase to xanthine oxidase in ischemic rat liver and kidney
McKelvey, 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×
“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].”
Background
Xanthine oxidase activity in human tissues and its inhibition by allopurinol (4-hydroxypyrazolo[3,4-d] pyrimidine).
Watts, R. W. E., Watts, J. E. M., & Seegmiller, J. E. (1965) · PubMed · Cited by 151
Mutation of Human Molybdenum Cofactor Sulfurase Gene Is Responsible for Classical Xanthinuria Type II
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×
“, XOR deficiency [104].”
Xanthine oxidase activity in rat pulmonary artery endothelial cells and its alteration by activated neutrophils.
Phan, S. H., Gannon, D. E., Varani, J., Ryan, U. S., & Ward, P. A. (1989) · PubMed Central · Cited by 147
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
Xanthine dehydrogenase and xanthine oxidase activity and gene expression in renal epithelial cells. Cytokine and steroid regulation.
Pfeffer, K. D., Huecksteadt, T. P., & Hoidal, J. R. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.153.4.1789 · Cited by 145
Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): Structural analysis of the protein and chromosomal location of the gene
Ichida, 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
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
Milk xanthine oxidase type D (dehydrogenase) and type O (oxidase). Purification, interconversion and some properties
Battelli, M. G., Lorenzoni, E., & Stirpe, F. (1973) · Biochemical Journal · doi:10.1042/bj1310191 · Cited by 141
Self-citation
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×
“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].”
Background
Nitrite confers protection against myocardial infarction: Role of xanthine oxidoreductase, NADPH oxidase and KATP channels
Baker, 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
Regulation of xanthine dehydrogenase and xanthine oxidase activity and gene expression in cultured rat pulmonary endothelial cells.
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×
“Additionally, XOR activity was up-regulated by IFNγ in rat lung endothelial cells [93].”
Background
Xanthine 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×
“to vascular lining was shown to be heparin reversible in studies with cultured endothelial cells [189].”
Background
Functional regulation of xanthine oxidoreductase expression and localization in the mouse mammary gland: evidence of a role in lipid secretion
McManaman, 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×
“until lactation followed by decreasing levels with mammary involution [84].”
Background
Circulating xanthine oxidase mediates lung neutrophil sequestration after intestinal ischemia-reperfusion
Terada, 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×
“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”
Background
Glutamate Neurotoxicity in Rat Cerebellar Granule Cells: A Major Role for Xanthine Oxidase in Oxygen Radical Formation
Atlante, 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
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
Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia
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×
“sion, and hypertriglyceridaemia and prevented an increase in fasting plasma insulin in rats with fructose-induced metabolic syndrome [282].”
Background
Molecular cloning of a cDNA coding for mouse liver xanthine dehydrogenase. Regulation of its transcript by interferons in vivo
Terao, M., Cazzaniga, G., Ghezzi, P., Bianchi, M., Francesco Falciani, B., Perani, P., & Garattini, E. (1992) · Biochemical Journal · doi:10.1042/bj2830863 · Cited by 117
The Effect of Xanthine Oxidase Inhibition Upon Ejection Fraction in Heart Failure Patients: La Plata Study
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×
“The treatment significantly improved the left ventricular ejection fraction only in 21 patients who exhibited this initial parameter lower or equal to 40% [261].”
Background
Human 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×
“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].”
Background
Organ distribution and molecular forms of human xanthine dehydrogenase/xanthine oxidase protein.
Sarnesto, A., Linder, N., & Raivio, K. O. (1996) · PubMed · Cited by 114
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×
“mice [179], and in fructose-induced hyperuricaemic mice [180].”
Background
Preconditioning protects liver and lung damage in rat liver transplantation: Role of xanthine/xanthine oxidase
Fernández, 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×
“tion of xanthine and XOR to pre-conditioned rats [158].”
Background
A Reappraisal of Xanthine Dehydrogenase and Oxidase in Hypoxic Reperfusion Injury: the Role of NADH as an Electron Donor
Zhang, 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×
“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].”
Background
Ischemic preconditioning: a defense mechanism against the reactive oxygen species generated after hepatic ischemia reperfusion1
Peralta, 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×
“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”
Background
Role 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
Upregulation of Xanthine Oxidase by Lipopolysaccharide, Interleukin-1, and Hypoxia: Role in Acute Lung Injury
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
Polydatin ameliorates renal injury by attenuating oxidative stress-related inflammatory responses in fructose-induced urate nephropathic mice
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×
“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].”
Background
Nitric Oxide Synthase and Xanthine Oxidase Activities in the Spermatic Vein of Patients with Varicocele: A Potential Role for Nitric Oxide and Peroxynitrite in Sperm Dysfunction
Mitropoulos, 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×
“due to reduced blood flow in the dilated varicocele vein [219].”
Background
Effects 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×
“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].”
Background
Enhanced activity of the free radical producing enzyme xanthine oxidase in hypoxic rat liver. Regulation and pathophysiologic significance.
Brass, C. A., Narciso, J. P., & Gollan, J. L. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115013 · Cited by 101
Liver ischemia-reperfusion increases pulmonary permeability in rat: role of circulating xanthine oxidase
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×
“leased from the liver after ischaemia/reperfusion, in which XOR activity decreased in hepatic tissue and increased in the effluent perfusate [193].”
Background
Intestinal 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×
“cirrhotic rats [136]; and in rat brain following in vivo acute ammonia intoxication [137].”
Background
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 100 · cited 2×
“Therefore, it is not simple to identify the specific role of these two enzymes in cardiovascular diseases (reviewed in [292]).”
Background
Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease
Baldus, 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×
“artery disease [260].”
Xanthine oxidoreductase in human mammary epithelial cells: activation in response to inflammatory cytokines
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
Serum 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×
“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]).”
Background
Tourniquet-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
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
Oxidation 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 95 · cited 2×
“[200,211,212], and viral infection [61,62,163,200–203].”
Background
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×
“in the plasma of hypoxic subjects, such as patients with adult respiratory distress syndrome [217] and preterm newborn babies [218].”
Background
Gut 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×
“molybdenum-depleted diet abolished these alterations, suggesting a XOR-dependent neutrophil mechanism in the pathogenesis of remote organ injury [236].”
Background
Neutrophil 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×
“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].”
Background
Allopurinol Use Yields Potentially Beneficial Effects on Inflammatory Indices in Those With Recent Ischemic Stroke
Muir, 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
Transient reduction in myocardial free oxygen radical levels is involved in the improved cardiac function and structure after long-term allopurinol treatment initiated in established chronic heart failure
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×
“established chronic heart failure [254].”
cDNA cloning, characterization, and tissue-specific expression of human xanthine dehydrogenase/xanthine oxidase.
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
Elevated levels of xanthine oxidase in serum of patients with inflammatory and autoimmune rheumatic diseases
Miesel, R., & Zuber, M. A. (1993) · Inflammation · doi:10.1007/bf00914193 · Cited by 87 · cited 1×
“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].”
Background
Conversion of xanthine dehydrogenase into xanthine oxidase in rat liver and plasma at the onset of reperfusion after ischemia
Kooij, 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×
“After being released into plasma, XOR is rapidly converted to the XO form [124,227,232].”
Background
Xanthine oxidase inhibitor tungsten prevents the development of atherosclerosis in ApoE knockout mice fed a Western-type diet
Schröder, 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
A re-evaluation of the tissue distribution and physiology of xanthine oxidoreductase
Kooij, A. (1994) · The Histochemical Journal · doi:10.1007/bf00174006 · Cited by 85 · cited 1×
“(reviewed in [3]) until almost half a century ago, when mammalian XOR was shown to be a dehydrogenase in its native state [40,41].”
Background
Allopurinol improves endothelial function and reduces oxidant-inflammatory enzyme of myeloperoxidase in metabolic syndrome
Yiğiner, 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 85 · cited 1×
“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…”
Background
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×
“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…”
Background
A novel mechanism for the generation of superoxide anions in hematoporphyrin derivative-mediated cutaneous photosensitization. Activation of the xanthine oxidase pathway.
Athar, M., Elmets, C. A., Bickers, D. R., & Mukhtar, H. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113993 · Cited by 84 · cited 1×
“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”
Background
Xanthine Oxidase Inhibition With Febuxostat Attenuates Systolic Overload-Induced Left Ventricular Hypertrophy and Dysfunction in Mice
Xu, 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×
“induced left ventricular hypertrophy and dysfunction in mice [298].”
Background
Is 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
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×
“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].”
Background
Tissue- and cell-specific expression of mouse xanthine oxidoreductase gene in vivo: regulation by bacterial lipopolysaccharide
Kurosaki, M., Calzi, M. L., Scanziani, E., Garattini, E., & Terao, M. (1995) · Biochemical Journal · doi:10.1042/bj3060225 · Cited by 79 · cited 1×
“, liver and intestine inmice [44] and humans [45].”
Background
Anti‐nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A1adenosine receptors
Schmidt, 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×
“This is an open access article under anti-nociceptive effect of theXOR inhibitor allopurinol inmice [6].”
Background
Enhanced 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×
“The administration of IFN or IFN-inducers to mice stimulated a marked increase of XOR activity in different organs [90], particularly”
Background
Simultaneous 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×
“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
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
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×
“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].”
Background
Purification 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×
“XOR can be found in human milk, although with a lower activity compared with cow milk [57,58].”
BackgroundInfluential
Xanthine 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×
“viral infections, including lung [95], brain [96], and liver [97] in mouse pathology and liver in human pathology [54].”
BackgroundSelf-citation
Are either or both hyperuricemia and xanthine oxidase directly toxic to the vasculature? A critical appraisal
Neogi, 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×
“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×
“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].”
Background
Xanthine oxidase inhibition ameliorates cardiovascular dysfunction in dogs with pacing-induced heart failure
Amado, 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 72 · cited 1×
“lopurinolwas able to prevent increases in systemic vasoconstriction and was able to improve myocardial contractility [253].”
Background
The 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×
“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]).”
Background
Milk 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×
“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]).”
Background
A 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×
“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].”
Background
Alterations of nitric oxide synthase and xanthine oxidase activities of human keratinocytes by ultraviolet B radiation
Deliconstantinos, G., Villiotou, V., & Stavrides, J. C. (1996) · Biochemical Pharmacology · doi:10.1016/0006-2952(96)00110-4 · Cited by 69
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
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
The role of oxidants and reactive nitrogen species in irritable bowel syndrome: A potential etiological explanation
Gürel, A. (2013) · Medical Science Monitor · doi:10.12659/msm.889068 · Cited by 68 · cited 1×
“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].”
Background
Lung 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×
“, with liver injury and elevated circulating XOR activity [184,237].”
Background
Glycaemic control in relation to xanthine oxidase and antioxidant indices in Malaysian Type 2 diabetes patients
Kuppusamy, U. R., Indran, M., & Rokiah, P. (2005) · Diabetic Medicine · doi:10.1111/j.1464-5491.2005.01630.x · Cited by 66 · cited 1×
“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].”
Background
Xanthine 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×
“gene expression, whichmay be regulated by nutritional factors, oxygen tension, steroid hormones [73], phorbol esters [74], regenerative”
Background
Mononuclear 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×
“cells and the production of ROS, peroxynitrites, and cytokines [247,248].”
Background
Upregulation 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×
“Additionally, tobacco smoke condensate up-regulated XOR activity in pulmonary endothelial cells by increasing XOR mRNA expression and XOR gene promoter activity [79].”
Background
Serum 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×
“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-citation
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×
“of hypoxanthine to xanthine and the latter to uric acid as the terminal steps of purine degradation in the highest primates [1].”
Background
Sequential activation of JAKs, STATs and xanthine dehydrogenase/oxidase by hypoxia in lung microvascular endothelial cells
Wang, 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 63
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
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×
“Elevated plasma concentrations of XOR were observed during reperfusion after liver transplantation compared with preoperative levels [226].”
Background
Murine epidermal xanthine oxidase activity: correlation with degree of hyperplasia induced by tumor promoters.
Pence, B. C., & Reiners, J. J. (1987) · PubMed · Cited by 61
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
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×
“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].”
Background
Use 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×
“role of XOR-produced ROS in this model of eye damage [169].”
Background
12-O-tetradecanoylphorbol-13-acetate-dependent induction of xanthine dehydrogenase and conversion to xanthine oxidase in murine epidermis.
Reiners, J. J., Pence, B. C., Barcus, M. C. S., & Cantú, A. R. (1987) · PubMed · Cited by 59
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×
“, liver and intestine inmice [44] and humans [45].”
Background
Intermediate 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×
“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]).”
BackgroundInfluential
The 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×
“(reviewed in [3]) until almost half a century ago, when mammalian XOR was shown to be a dehydrogenase in its native state [40,41].”
Background
Oxidative Stress-Associated Vascular Aging Is Xanthine Oxidase-Dependent but not NAD(P)H Oxidase-Dependent
Newaz, M., Yousefipour, Z., & Oyekan, A. (2006) · Journal of Cardiovascular Pharmacology · doi:10.1097/01.fjc.0000245402.62864.0a · Cited by 57 · cited 1×
“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].”
Background
Aluminium 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×
“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.”
Background
Involvement of xanthine oxidase and hypoxia-inducible factor 1 in Toll-like receptor 7/8-mediated activation of caspase 1 and interleukin-1β
Nicholas, 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 57
MODIFICATION 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×
“to pre-conditioning procedures [152].”
Xanthine Oxidase Inhibitor Febuxostat as a Novel Agent Postulated to Act Against Vascular Inflammation
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
Maternal and fetal plasma adenosine deaminase, xanthine oxidase and malondialdehyde levels in pre‐eclampsia
Karabulut, A. B., Kafkaslı, A., Burak, F., & Gözükara, E. M. (2004) · Cell Biochemistry and Function · doi:10.1002/cbf.1152 · Cited by 56
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×
“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].”
Method
Disproportionate enhancement of myocardial contractility by the xanthine oxidase inhibitor oxypurinol in failing rat myocardium
Kögler, H. (2003) · Cardiovascular Research · doi:10.1016/s0008-6363(03)00512-1 · Cited by 53 · cited 1×
“XOR activity level, which was more pronounced in failing rat myocardium [255].”
Background
Role 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
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
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×
“arterial wave reflection as a measure of vascular function [262].”
Background
Xanthine Oxidoreductase Promotes the Inflammatory State of Mononuclear Phagocytes through Effects on Chemokine Expression, Peroxisome Proliferator-activated Receptor-γ Sumoylation, and HIF-1α
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 52
Effects of acute ethanol administration on the hepatic xanthine dehydrogenase/oxidase system in the rat.
Sultatos, L. G. (1988) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22210-8 · Cited by 52 · cited 1×
“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”
Background
Gastric 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×
“protective towards the decrease of gastric intramucosal pH induced by hepatoenteric ischaemia/reperfusion, which is considered a marker of multiple organ injury [185].”
Background
Xanthine oxidase and superoxide radicals in portal triad crossclamping-induced microvascular reperfusion injury of the liver
Müller, 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
Liver 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 50 · cited 1×
“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”
Background
Xanthine Oxidase Contributes to Host Defense againstBurkholderia cepaciain the p47phox−/−Mouse Model of Chronic Granulomatous Disease
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
Distribution of xanthine oxidoreductase activity in human tissues — a histochemical and biochemical study
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×
“as well as with intracellular organelles, such as peroxisomes [48] (reviewed in [49]).”
Background
NADH oxidase activity of rat and human liver xanthine oxidoreductase: potential role in superoxide production
Maia, 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 49 · cited 1×
“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].”
Background
Effects of hypoxia and ethanol on xanthine oxidase of isolated rat hepatocytes: Conversion from D to O form and leakage from cells
Battelli, M. G., Abbondanza, A., & Stirpe, F. (1992) · Chemico-Biological Interactions · doi:10.1016/0009-2797(92)90093-z · Cited by 47
Self-citation
Febuxostat Improves the Local and Remote Organ Changes Induced by Intestinal Ischemia/Reperfusion in Rats
Shafik, A. N. (2012) · Digestive Diseases and Sciences · doi:10.1007/s10620-012-2391-1 · Cited by 47 · cited 1×
“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].”
Background
Reoxygenation injury in isolated hepatocytes: Cell death precedes conversion of xanthine dehydrogenase to xanthine oxidase
de GROOT, H., & Littauer, A. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)81080-5 · Cited by 46 · cited 1×
“Furthermore, XOR was released from the severely injured cells before the XDH/XO conversion occurred [145].”
Background
Xanthine 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
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×
“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”
Background
Lung 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×
“increase of XOR activity in plasma,whichwas partially related to the appearance of histamine in plasma [168].”
Background
Cloning and expression in vitro of human xanthine dehydrogenase/oxidase
Saksela, M., & Raivio, K. O. (1996) · Biochemical Journal · doi:10.1042/bj3150235 · Cited by 45 · cited 1×
“in vitro [68–70].”
Conversion of xanthine dehydrogenase to xanthine oxidase in bovine carotid artery endothelial cells induced by activated neutrophils: involvement of adhesion molecules
Wakabayashi, Y., Fujita, H., Morita, I., Kawaguchi, H., & Murota, S. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(94)00202-p · Cited by 44 · cited 1×
“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…”
Background

Research works printed but not linked: 1

Nguyen, 1986, Plant xanthine dehydrogenase: its distribution, properties and function, Physiol. Vég., 24, 263

Sorted by citations

Lifestyle, oxidative stress, and antioxidants: Back and forth in the pathophysiology of chronic diseases
Sharifi-Rad, M., Anil Kumar, N. V., Zucca, P., Varoni, E. M., Dini, L., Panzarini, E., Rajkovic, J., Tsouh Fokou, P. V., Azzini, E., Peluso, I., et al. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00694 · Cited by 1,971
Self-citation
Reperfusion injury and reactive oxygen species: The evolution of a concept
Granger, D. N., & Kvietys, P. R. (2015) · Redox Biology · doi:10.1016/j.redox.2015.08.020 · Cited by 1,550
“The binding of circulating XO to vascular endothelial cells has been invoked to explain the effectiveness of xanthine oxidase inhibitors in blunting the I/R injury response in tissues that exhibit low XO activity [131].”
Background
Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases
Incalza, M. A., D’Oria, R., Natalicchio, A., Perrini, S., Laviola, L., & Giorgino, F. (2017) · Vascular Pharmacology · doi:10.1016/j.vph.2017.05.005 · Cited by 1,419
“Finally, it should be mentioned that under specific pathological conditions, such as liver and intestine diseases [80] and hypoxia [81], XDH is released to the circulation and converted to the XO form that binds to”
Background
Clinical Relevance of Biomarkers of Oxidative Stress
Frijhoff, J., Winyard, P. G., Žarković, N., Davies, S. S., Stocker, R., Cheng, D., Knight, A. R., Taylor, E., Oettrich, J., Ruskovska, T., et al. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6317 · Cited by 918
“This led to several, ongoing clinical trials with XO inhibitors in CVD and prompted many studies to measure circulating XO (12).”
Result
Sources 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

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Authors: Battelli, M. G., Bolognesi, A., & Polito, L.
Affiliations: University of Bologna (IT)
Corresponding author: Bolognesi, Andrea
Polito, Letizia
ORCID: Battelli, Maria Giulia
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)
DOI: 10.1016/j.bbadis.2014.05.022
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: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/3.0/ (vor)
Locations: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
INFM-OAR (INFN Catania) (submittedVersion, cc-by-nc-nd)
Funders: Alma Mater Studiorum‐University of Bologna
Pallotti Legacies for Cancer Research
Topics: Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords: xanthine oxidoreductase, purine degradation, uric acid, oxidative stress, reactive oxygen species, endothelial cells, vascular response, inflammation, thrombosis, cardiovascular disease, metabolic disorders, serum enzyme levels
MeSH terms: Animals, Cardiovascular Diseases, Humans, Xanthine Dehydrogenase, Metabolic Syndrome

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Pathophysiology of circulating xanthine oxidoreductase: New emerging roles for a multi-tasking enzyme

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