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Current Biotechnology

Editor-in-Chief

ISSN (Print): 2211-5501
ISSN (Online): 2211-551X

Review Article

Xanthine Oxidase Perspective in Human Health

Author(s): Santwona Dash, Sabita Pattanayak, Barsarani Jena, Manasa K. Panda and Yengkhom D. Singh*

Volume 9, Issue 4, 2020

Page: [255 - 262] Pages: 8

DOI: 10.2174/2211550109999201113101040

Price: $65

Abstract

Xanthine oxidase (XO) is an essential enzyme in catalyzing the hydroxylation of hypoxanthine to xanthine and uric acid in the kidney. Excessive formation of uric acid can lead to hyperuricemia (HUA), a condition caused by excess uric acid contamination in the blood. HUA is responsible for various diseases in the body, such as gout, cardiovascular, and renal failure. It is also associated with numerous inflammatory diseases and their metabolic pathways, including tumors, chronic hypoxia, renal injury, and hypertension. XO is a superoxide producing enzyme usually confined to lungs, liver, and blood serum. Blood assay and diagnostics for XO help in a better understanding of its associated diseases in the human body. The mechanism of how XO is released in the bloodstream is a matter of debate in medical science. In the current review article, we comprehensively discussed the role of XO in human health, inhibitors, and their regulation, isolation, and extractions of inhibitors from plants, types, and their activities towards the human health perspective are described.

Keywords: Xanthine oxidase, hyperuricemia, bioactive molecules, inhibitors, enzymes, human health.

Graphical Abstract
[1]
Cantu-Medellin N, Kelley EE. Xanthine oxidoreductase-catalyzed reactive species generation: A process in critical need of reevaluation. Redox Biol 2013; 1(1): 353-8.
[http://dx.doi.org/10.1016/j.redox.2013.05.002] [PMID: 24024171]
[2]
Borges F, Fernandes E, Roleira F. Progress towards the discovery of xanthine oxidase inhibitors. Curr Med Chem 2002; 9(2): 195-217.
[http://dx.doi.org/10.2174/0929867023371229] [PMID: 11860355]
[3]
Šmelcerović A, Tomović K, Šmelcerović Ž, et al. Xanthine oxidase inhibitors beyond allopurinol and febuxostat; An overview and selection of potential leads based on in silico calculated physico-chemical properties, predicted pharmacokinetics and toxicity. Eur J Med Chem 2017; 135: 491-516.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.031] [PMID: 28478180]
[4]
Zhang Y, Cheng H, Xu J, Lu L. Functional component of differentiation, apoptosis and aggressiveness of tumors. Cell Biol 2016; 4(4): 24-30.
[5]
Kuwabara Y, Nishino T, Okamoto K, et al. Unique amino acids cluster for switching from the dehydrogenase to oxidase form of xanthine oxidoreductase. Proc Natl Acad Sci USA 2003; 100(14): 8170-5.
[http://dx.doi.org/10.1073/pnas.1431485100] [PMID: 12817083]
[6]
Enroth C, Eger BT, Okamoto K, Nishino T, Nishino T, Pai EF. Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: Structure-based mechanism of conversion. Proc Natl Acad Sci USA 2000; 97(20): 10723-8.
[http://dx.doi.org/10.1073/pnas.97.20.10723] [PMID: 11005854]
[7]
Battelli MG, Bolognesi A, Polito L. Pathophysiology of circulating xanthine oxidoreductase: New emerging roles for a multi-tasking enzyme. Biochim Biophys Acta 2014; 1842(9): 1502-17.
[http://dx.doi.org/10.1016/j.bbadis.2014.05.022] [PMID: 24882753]
[8]
Huang CC, Chen KL, Cheung CHA, Chang JY. Autophagy induced by cathepsin S inhibition induces early ROS production, oxidative DNA damage, and cell death via xanthine oxidase. Free Radic Biol Med 2013; 65: 1473-86.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.07.020] [PMID: 23892358]
[9]
Lin J, Xu P, LaVallee P, Hoidal JR. Identification of proteins binding to E-Box/Ku86 sites and function of the tumor suppressor SAFB1 in transcriptional regulation of the human xanthine oxidoreductase gene. J Biol Chem 2008; 283(44): 29681-9.
[http://dx.doi.org/10.1074/jbc.M802076200] [PMID: 18772145]
[10]
Harrison R. Physiological roles of xanthine oxidoreductase. Drug Metab Rev 2004; 36(2): 363-75.
[http://dx.doi.org/10.1081/DMR-120037569] [PMID: 15237859]
[11]
Harrison R. Structure and function of xanthine oxidoreductase: Where are we now? Free Radic Biol Med 2002; 33(6): 774-97.
[http://dx.doi.org/10.1016/S0891-5849(02)00956-5] [PMID: 12208366]
[12]
Okamoto K, Kusano T, Nishino T. Chemical nature and reaction mechanisms of the molybdenum cofactor of xanthine oxidoreductase. Curr Pharm Des 2013; 19(14): 2606-14.
[http://dx.doi.org/10.2174/1381612811319140010] [PMID: 23116398]
[13]
Pritsos CA. Cellular distribution, metabolism and regulation of the xanthine oxidoreductase enzyme system. Chem Biol Interact 2000; 129(1-2): 195-208.
[http://dx.doi.org/10.1016/S0009-2797(00)00203-9] [PMID: 11154741]
[14]
Ventom AM, Deistung J, Bray RC. The isolation of demolybdo xanthine oxidase from bovine milk. Biochem J 1988; 255(3): 949-56.
[http://dx.doi.org/10.1042/bj2550949] [PMID: 2850803]
[15]
Schardinger F. Über das Verhalten der Kuhmilch gegen Methylenblau und seine Verwendung zur Unterscheidung von ungekochter und gekochter Milch. Zeitschrift für Lebensmitteluntersuchung und-Forschung 1902; 5(22): 1113-21.
[16]
Morgan EJ, Stewart CP, Hopkins FG. On the anaerobic and aerobic oxidation of xanthin and hypoxanthin by tissues and by milk. Proc R Soc Lond, B 1922; 94(657): 109-31.
[http://dx.doi.org/10.1098/rspb.1922.0047]
[17]
Haas P, Hill TG. Observations on certain reducing and oxidising reactions in milk. Biochem J 1923; 17(6): 671-82.
[http://dx.doi.org/10.1042/bj0170671] [PMID: 16743203]
[18]
Haas P, Lee B. Further observations on certain reducing and oxidising reactions in milk. Biochem J 1924; 18(3-4): 614-20.
[http://dx.doi.org/10.1042/bj0180614] [PMID: 16743438]
[19]
Candan F. Effect of Rhus coriaria L. (Anacardiaceae) on superoxide radical scavenging and xanthine oxidase activity. J Enzyme Inhib Med Chem 2003; 18(1): 59-62.
[http://dx.doi.org/10.1080/1475636031000069273] [PMID: 12751822]
[20]
Mittal A, Phillips AR, Loveday B, Windsor JA. The potential role for xanthine oxidase inhibition in major intra-abdominal surgery. World J Surg 2008; 32(2): 288-95.
[http://dx.doi.org/10.1007/s00268-007-9336-4] [PMID: 18074171]
[21]
Cos P, Ying L, Calomme M, et al. Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J Nat Prod 1998; 61(1): 71-6.
[http://dx.doi.org/10.1021/np970237h] [PMID: 9461655]
[22]
Kelley EE, Khoo NK, Hundley NJ, Malik UZ, Freeman BA, Tarpey MM. Hydrogen peroxide is the major oxidant product of xanthine oxidase. Free Radic Biol Med 2010; 48(4): 493-8.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.11.012] [PMID: 19941951]
[23]
Dawson J, Walters M. Uric acid and xanthine oxidase: Future therapeutic targets in the prevention of cardiovascular disease? Br J Clin Pharmacol 2006; 62(6): 633-44.
[http://dx.doi.org/10.1111/j.1365-2125.2006.02785.x] [PMID: 21894646]
[24]
Nieto FJ, Iribarren C, Gross MD, Comstock GW, Cutler RG. Uric acid and serum antioxidant capacity: A reaction to atherosclerosis? Atherosclerosis 2000; 148(1): 131-9.
[http://dx.doi.org/10.1016/S0021-9150(99)00214-2] [PMID: 10580179]
[25]
Burke A, Smyth E, FitzGerald GA. Analgesic-antipyretic agents; pharmacotherapy of gout. The pharmacological basis of therapeutics 2006; 1: 706.
[26]
Choi HK, Mount DB, Reginato AM. Pathogenesis of gout. Ann Intern Med 2005; 143(7): 499-516.
[http://dx.doi.org/10.7326/0003-4819-143-7-200510040-00009] [PMID: 16204163]
[27]
Umamaheswari M, AsokKumar K, Somasundaram A, Sivashanmugam T, Subhadradevi V, Ravi TK. Xanthine oxidase inhibitory activity of some Indian medical plants. J Ethnopharmacol 2007; 109(3): 547-51.
[http://dx.doi.org/10.1016/j.jep.2006.08.020] [PMID: 17014977]
[28]
Pacher P, Nivorozhkin A, Szabó C. Therapeutic effects of xanthine oxidase inhibitors: Renaissance half a century after the discovery of allopurinol. Pharmacol Rev 2006; 58(1): 87-114.
[http://dx.doi.org/10.1124/pr.58.1.6] [PMID: 16507884]
[29]
Tsutomu H, Taeko Y, Rieko Y, et al. Planta Med 1991; 57: 83-4.
[http://dx.doi.org/10.1055/s-2006-960028] [PMID: 2062964]
[30]
Mehta SK, Nayeem N. Natural xanthine oxidase inhibitors for management of gout: A review. Research and reviews: Journal of medical and health sciences 2014; 1-3.
[31]
Halliwell B, Gutteridge JM, Cross CE. Free radicals, antioxidants, and human disease: Where are we now? J Lab Clin Med 1992; 119(6): 598-620.
[PMID: 1593209]
[32]
Iwanaga T, Kobayashi D, Hirayama M, Maeda T, Tamai I. Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone. Drug Metab Dispos 2005; 33(12): 1791-5.
[http://dx.doi.org/10.1124/dmd.105.006056] [PMID: 16135657]
[33]
Ibrahim MA, Masoud HM, Darwish DA, Esa SS, Zaahkouk SA. Purification and characterization of xanthine oxidase from liver of the water buffalo Bubalus bubalis. J Appl Pharm Sci 2015; 5(11): 63-8.
[http://dx.doi.org/10.7324/JAPS.2015.501110]
[34]
Fox PF, Kelly AL. Indigenous enzymes in milk: Overview and historical aspects-Part 1. Int Dairy J 2006; 16(6): 500-16.
[http://dx.doi.org/10.1016/j.idairyj.2005.09.013]
[35]
Ball EG. Xanthine oxidase: Purification and properties. J Biol Chem 1939; 128: 51-67.
[36]
Nelson CA, Handler P. Preparation of bovine xanthine oxidase and the subunit structures of some iron flavoproteins. J Biol Chem 1968; 243(20): 5368-73.
[PMID: 5702049]
[37]
Waud WR, Brady FO, Wiley RD, Rajagopalan KV. A new purification procedure for bovine milk xanthine oxidase: Effect of proteolysis on the subunit structure. Arch Biochem Biophys 1975; 169(2): 695-701.
[http://dx.doi.org/10.1016/0003-9861(75)90214-3] [PMID: 1180567]
[38]
Zhang Y, Xin Y, Yang H, et al. Novel affinity purification of xanthine oxidase from Arthrobacter M3. J Chromatogr B Analyt Technol Biomed Life Sci 2012; 906: 19-24.
[http://dx.doi.org/10.1016/j.jchromb.2012.08.007] [PMID: 22954965]
[39]
Nishino T, Okamoto K, Eger BT, Pai EF, Nishino T. Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J 2008; 275(13): 3278-89.
[http://dx.doi.org/10.1111/j.1742-4658.2008.06489.x] [PMID: 18513323]
[40]
Nepali K, Agarwal A, Sapra S, et al. N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase inhibitors. Bioorg Med Chem 2011; 19(18): 5569-76.
[http://dx.doi.org/10.1016/j.bmc.2011.07.039] [PMID: 21862335]
[41]
Lin S, Zhang G, Pan J, Gong D. Deciphering the inhibitory mechanism of genistein on xanthine oxidase in vitro. J Photochem Photobiol B 2015; 153: 463-72.
[http://dx.doi.org/10.1016/j.jphotobiol.2015.10.022] [PMID: 26584360]
[42]
Dhiman R, Sharma S, Singh G, Nepali K, Singh Bedi PM. Design and synthesis of aza-flavones as a new class of xanthine oxidase inhibitors. Arch Pharm (Weinheim) 2013; 346(1): 7-16.
[http://dx.doi.org/10.1002/ardp.201200296] [PMID: 23076715]
[43]
Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol 2000; 190(3): 255-66.
[http://dx.doi.org/10.1002/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO;2-6] [PMID: 10685060]
[44]
Hewinson J, Stevens CR, Millar TM. Vascular physiology and pathology of circulating xanthine oxidoreductase: From nucleotide sequence to functional enzyme. Redox Rep 2004; 9(2): 71-9.
[http://dx.doi.org/10.1179/135100004225004797] [PMID: 15231061]
[45]
Poss WB, Huecksteadt TP, Panus PC, Freeman BA, Hoidal JR. Regulation of xanthine dehydrogenase and xanthine oxidase activity by hypoxia. Am J Physiol 1996; 270(6 Pt 1): L941-6.
[PMID: 8764218]
[46]
Terada LS, Piermattei D, Shibao GN, McManaman JL, Wright RM. Hypoxia regulates xanthine dehydrogenase activity at pre- and posttranslational levels. Arch Biochem Biophys 1997; 348(1): 163-8.
[http://dx.doi.org/10.1006/abbi.1997.0367] [PMID: 9390187]
[47]
Parks DA, Bulkley GB, Granger DN. Role of oxygen-derived free radicals in digestive tract diseases. Surgery 1983; 94(3): 415-22.
[PMID: 6351311]
[48]
Sikora J, Orlov SN, Furuya K, Grygorczyk R. Hemolysis is a primary ATP-release mechanism in human erythrocytes. Blood 2014; 124(13): 2150-7.
[http://dx.doi.org/10.1182/blood-2014-05-572024] [PMID: 25097178]
[49]
Della Corte E, Stirpe F. The regulation of xanthine oxidase. Inhibition by reduced nicotinamide-adenine dinucleotide of rat liver xanthine oxidase type D and of chick liver xanthine dehydrogenase. Biochem J 1970; 117(1): 97-100.
[http://dx.doi.org/10.1042/bj1170097] [PMID: 4316091]
[50]
Symons MC, Taiwo FA, Petersen RL. Electron addition to xanthine oxidase. An electron spin resonance study of the effects of ionizing radiation. J Chem Soc, Faraday Transactions 1. Physical Chemistry in Condensed Phases 1989; 85(12): 4063-74.
[51]
Kostić DA, Dimitrijević DS, Stojanović GS, Palić IR, Đorđević AS, Ickovski JD. Xanthine oxidase: Isolation, assays of activity, and inhibition. Journal of Chemistry 2015.
[http://dx.doi.org/10.1155/2015/294858]
[52]
Spector T. Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. Biochem Pharmacol 1988; 37(2): 349-52.
[http://dx.doi.org/10.1016/0006-2952(88)90739-3] [PMID: 2829916]
[53]
Hosoya T, Ogawa Y, Hashimoto H, Ohashi T, Sakamoto R. Comparison of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout: a phase 3, multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study. J Clin Pharm Ther 2016; 41(3): 290-7.
[http://dx.doi.org/10.1111/jcpt.12391] [PMID: 27109450]
[54]
Selloum L, Reichl S, Müller M, Sebihi L, Arnhold J. Effects of flavonols on the generation of superoxide anion radicals by xanthine oxidase and stimulated neutrophils. Arch Biochem Biophys 2001; 395(1): 49-56.
[http://dx.doi.org/10.1006/abbi.2001.2562] [PMID: 11673865]
[55]
Chiang HC, Lo YJ, Lu FJ. Xanthine oxidase inhibitors from the leaves of Alsophila spinulosa (Hook) Tryon. J Enzyme Inhib 1994; 8(1): 61-71.
[http://dx.doi.org/10.3109/14756369409040777] [PMID: 7539070]
[56]
Muraoka S, Miura T. Inhibition of xanthine oxidase by phytic acid and its antioxidative action. Life Sci 2004; 74(13): 1691-700.
[http://dx.doi.org/10.1016/j.lfs.2003.09.040] [PMID: 14738912]
[57]
Azmi SM, Jamal P, Amid A. Purification of Xanthine oxidaseinhibitor from carica papaya leaves using reversed phase flash column chromatography (RPFCC)-high performance thin layer chromatography (HPTLC). Aust J Basic Appl Sci 2012; 6(1): 117-22.
[58]
Sahin H, Aliyazicioglu R, Yildiz O, Kolayli S, Innocenti A, Supuran CT. Honey, pollen, and propolis extracts show potent inhibitory activity against the zinc metalloenzyme carbonic anhydrase. J Enzyme Inhib Med Chem 2011; 26(3): 440-4.
[http://dx.doi.org/10.3109/14756366.2010.503610] [PMID: 20687792]
[59]
Sahin H. Honey as an apitherapic product: Its inhibitory effect on urease and xanthine oxidase. J Enzyme Inhib Med Chem 2016; 31(3): 490-4.
[PMID: 25942364]
[60]
Sweeney AP, Wyllie SG, Shalliker RA, Markham JL. Xanthine oxidase inhibitory activity of selected Australian native plants. J Ethnopharmacol 2001; 75(2-3): 273-7.
[http://dx.doi.org/10.1016/S0378-8741(01)00176-3] [PMID: 11297862]
[61]
Nessa F, Ismail Z, Mohamed N, Haris MR. Free radical-scavenging activity of organic extracts and of pure flavonoids of Blumea balsamifera DC leaves. Food Chem 2004; 88(2): 243-52.
[http://dx.doi.org/10.1016/j.foodchem.2004.01.041]
[62]
Villaseñor IM, Lamadrid MRA. Comparative anti-hyperglycemic potentials of medicinal plants. J Ethnopharmacol 2006; 104(1-2): 129-31.
[http://dx.doi.org/10.1016/j.jep.2005.08.067] [PMID: 16253452]
[63]
Gupta RK, Gangoliya SS, Singh NK. Reduction of phytic acid and enhancement of bioavailable micronutrients in food grains. J Food Sci Technol 2015; 52(2): 676-84.
[http://dx.doi.org/10.1007/s13197-013-0978-y] [PMID: 25694676]
[64]
Zhou JR, Erdman JW Jr. Phytic acid in health and disease. Crit Rev Food Sci Nutr 1995; 35(6): 495-508.
[http://dx.doi.org/10.1080/10408399509527712] [PMID: 8777015]
[65]
Chen L, Wang WY, Wang YP. Inhibitory effects of lithospermic acid on proliferation and migration of rat vascular smooth muscle cells. Acta Pharmacol Sin 2009; 30(9): 1245-52.
[http://dx.doi.org/10.1038/aps.2009.122] [PMID: 19701233]
[66]
Nile SH, Khobragade CN. Phytochemical analysis, antioxidant and xanthine oxidase inhibitory activity of Tephrosia purpurea Linn. root extract. Indian J Nat Prod Resour 2011; 2(1): 52-8.
[67]
Unno T, Sugimoto A, Kakuda T. Xanthine oxidase inhibitors from the leaves of Lagerstroemia speciosa (L.) Pers. J Ethnopharmacol 2004; 93(2-3): 391-5.
[http://dx.doi.org/10.1016/j.jep.2004.04.012] [PMID: 15234783]
[68]
Jiao RH, Ge HM, Shi H, Tan RX. An apigenin-derived xanthine oxidase inhibitor from Palhinhaea cernua. J Nat Prod 2006; 69(7): 1089-91.
[http://dx.doi.org/10.1021/np060038a] [PMID: 16872152]
[69]
Wang SY, Yang CW, Liao JW, Zhen WW, Chu FH, Chang ST. Essential oil from leaves of Cinnamomum osmophloeum acts as a xanthine oxidase inhibitor and reduces the serum uric acid levels in oxonate-induced mice. Phytomedicine 2008; 15(11): 940-5.
[http://dx.doi.org/10.1016/j.phymed.2008.06.002] [PMID: 18693097]
[70]
Murrell GA, Rapeport WG. Clinical pharmacokinetics of allopurinol. Clin Pharmacokinet 1986; 11(5): 343-53.
[http://dx.doi.org/10.2165/00003088-198611050-00001] [PMID: 3536254]
[71]
Schmidt HM, Kelley EE, Straub AC. The impact of xanthine oxidase (XO) on hemolytic diseases. Redox Biol 2019; 21: 101072.
[http://dx.doi.org/10.1016/j.redox.2018.101072] [PMID: 30580157]
[72]
Vinchi F, Costa da Silva M, Ingoglia G, et al. Hemopexin therapy reverts heme-induced proinflammatory phenotypic switching of macrophages in a mouse model of sickle cell disease. Blood 2016; 127(4): 473-86.
[http://dx.doi.org/10.1182/blood-2015-08-663245] [PMID: 26675351]
[73]
Vinchi F, De Franceschi L, Ghigo A, et al. Hemopexin therapy improves cardiovascular function by preventing heme-induced endothelial toxicity in mouse models of hemolytic diseases. Circulation 2013; 127(12): 1317-29.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.130179] [PMID: 23446829]
[74]
Yokoyama Y, Beckman JS, Beckman TK, et al. Circulating xanthine oxidase: Potential mediator of ischemic injury. Am J Physiol 1990; 258(4 Pt 1): G564-70.
[PMID: 2333969]
[75]
Battelli MG, Musiani S, Valgimigli M, et al. Serum xanthine oxidase in human liver disease. Am J Gastroenterol 2001; 96(4): 1194-9.
[http://dx.doi.org/10.1111/j.1572-0241.2001.03700.x] [PMID: 11316169]
[76]
Wortmann RL. Recent advances in the management of gout and hyperuricemia. Curr Opin Rheumatol 2005; 17(3): 319-24.
[http://dx.doi.org/10.1097/01.bor.0000162060.25895.a5] [PMID: 15838244]
[77]
Banister EW, Rajendra W, Mutch BJ. Ammonia as an indicator of exercise stress implications of recent findings to sports medicine. Sports Med 1985; 2(1): 34-46.
[http://dx.doi.org/10.2165/00007256-198502010-00004] [PMID: 3883458]

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