{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:24:42Z","timestamp":1785216282374,"version":"3.55.0"},"reference-count":26,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare of Japan","doi-asserted-by":"publisher","award":["23FC1009"],"award-info":[{"award-number":["23FC1009"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare of Japan","doi-asserted-by":"publisher","award":["20ek0109365h0003"],"award-info":[{"award-number":["20ek0109365h0003"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23FC1009"],"award-info":[{"award-number":["23FC1009"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20ek0109365h0003"],"award-info":[{"award-number":["20ek0109365h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative movement disorder associated with a loss of dopamine neurons in the substantia nigra. The diagnosis of PD is sensitive since it shows clinical features that are common with other neurodegenerative diseases. In addition, most symptoms arise at the late stage of the disease, where most dopaminergic neurons are already damaged. Several studies reported that oxidative stress is a key modulator in the development of PD. This condition occurs due to excess reactive oxygen species (ROS) production in the cellular system and the incapability of antioxidants to neutralize it. In this study, we focused on the pathology of PD by measuring serum xanthine oxidase (XO) activity, which is an enzyme that generates ROS. Interestingly, the serum XO activity of patients with PD was markedly upregulated compared to patients with other neurological diseases (ONDs) as a control. Moreover, serum XO activity in patients with PD showed a significant correlation with the disease severity based on the Hoehn and Yahr (HY) stages. The investigation of antioxidant status also revealed that serum uric acid levels were significantly lower in the severe group (HY \u2265 3) than in the ONDs group. Together, these results suggest that XO activity may contribute to the development of PD and might potentially be a biomarker for determining disease severity in patients with PD.<\/jats:p>","DOI":"10.3390\/biom14040490","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T07:55:54Z","timestamp":1713426954000},"page":"490","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Elevated Serum Xanthine Oxidase and Its Correlation with Antioxidant Status in Patients with Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Ratna Dini","family":"Haryuni","sequence":"first","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, University of Toyama, Toyama 930-8555, Japan"},{"name":"Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, National Research and Innovation Agency, Jakarta 10340, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamasa","family":"Nukui","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, University of Toyama, Toyama 930-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Lan","family":"Piao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, University of Toyama, Toyama 930-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2281-2486","authenticated-orcid":false,"given":"Takashi","family":"Shirakura","sequence":"additional","affiliation":[{"name":"Teijin Institute for Bio-Medical Research, Teijin Pharma Ltd., Tokyo 191-8512, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieko","family":"Matsui","sequence":"additional","affiliation":[{"name":"Teijin Institute for Bio-Medical Research, Teijin Pharma Ltd., Tokyo 191-8512, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Faculty of Data Science, Graduate School of Data Science, University of Shiga, 1-1-1 Banba, Hikone 522-8533, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kousuke","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, University of Toyama, Toyama 930-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunya","family":"Nakane","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, University of Toyama, Toyama 930-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Nakatsuji","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, University of Toyama, Toyama 930-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a009258","DOI":"10.1101\/cshperspect.a009258","article-title":"Parkinson\u2019s disease and parkinsonism: Neuropathology","volume":"2","author":"Dickson","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_3","first-page":"1817","article-title":"Damage to dopaminergic neurons by oxidative stress in Parkinson\u2019s disease (Review)","volume":"41","author":"Guo","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/1873-3468.12964","article-title":"Role of mitochondrial ROS in the brain: From physiology to neurodegeneration","volume":"592","author":"Angelova","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_5","first-page":"963520","article-title":"ROS and brain diseases: The good, the bad, and the ugly","volume":"2013","author":"Mitran","year":"2013","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wen, M., Zhou, B., Chen, Y.H., Ma, Z.L., Gou, Y., Zhang, C.L., Yu, W.F., and Jiao, L. (2017). Serum uric acid levels in patients with Parkinson\u2019s disease: A meta-analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173731"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.redox.2013.05.002","article-title":"Xanthine oxidoreductase-catalyzed reactive species generation: A process in critical need of reevaluation","volume":"1","author":"Kelley","year":"2013","journal-title":"Redox Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s10072-016-2782-8","article-title":"Serum glutathione peroxidase, xanthine oxidase, and superoxide dismutase activities and malondialdehyde levels in patients with Parkinson\u2019s disease","volume":"38","author":"Durak","year":"2017","journal-title":"Neurol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s11357-997-0012-2","article-title":"Xanthine dehydrogenase\/xanthine oxidase and oxidative stress","volume":"20","author":"Chung","year":"1997","journal-title":"Age"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"24438","DOI":"10.3390\/ijms141224438","article-title":"Oxidative stress and neurodegenerative disorders","volume":"14","author":"Li","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S0005-2728(99)00029-8","article-title":"Nitric oxide and cell death","volume":"1411","author":"Murphy","year":"1999","journal-title":"Biochim. Biophys. Acta (BBA)-Bioenerg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ijcard.2015.08.109","article-title":"Regulation of uric acid metabolism and excretion","volume":"213","author":"Maiuolo","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.12659\/MSM.899852","article-title":"Hyperuricemia-Related Diseases and Xanthine Oxidoreductase (XOR) Inhibitors: An Overview","volume":"22","author":"Chen","year":"2016","journal-title":"Med. Sci. Monit."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.tips.2016.06.007","article-title":"Targeting Oxidative Stress in Central Nervous System Disorders","volume":"37","author":"Patel","year":"2016","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"C1424","DOI":"10.1152\/ajpcell.1996.271.5.C1424","article-title":"Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and ugly","volume":"271","author":"Beckman","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1470380","DOI":"10.1155\/2021\/1470380","article-title":"The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors","volume":"2021","author":"Liu","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Battelli, M.G., Bortolotti, M., Bolognesi, A., and Polito, L. (2020). Pro-Aging Effects of Xanthine Oxidoreductase Products. Antioxidants, 9.","DOI":"10.3390\/antiox9090839"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Vida, C., Kobayashi, H., Garrido, A., Mart\u00ednez de Toda, I., Carro, E., Molina, J.A., and De la Fuente, M. (2019). Lymphoproliferation Impairment and Oxidative Stress in Blood Cells from Early Parkinson\u2019s Disease Patients. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030771"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e00598","DOI":"10.1002\/brb3.598","article-title":"Serum uric acid levels in Parkinson\u2019s disease and related disorders","volume":"7","author":"Sakuta","year":"2017","journal-title":"Brain Behav."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1002\/mds.21502","article-title":"Low plasma uric acid level in Parkinson\u2019s disease","volume":"22","author":"Annanmaki","year":"2007","journal-title":"Mov. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/ana.20663","article-title":"Serum uric acid levels and the risk of Parkinson disease","volume":"58","author":"Koudstaal","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_22","unstructured":"Investigators TPSGS-P (2014). Inosine to Increase Serum and Cerebrospinal Fluid Urate in Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol., 71, 141\u2013150."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.brainres.2014.03.031","article-title":"Allopurinol reduces levels of urate and dopamine but not dopaminergic neurons in a dual pesticide model of Parkinson\u2019s disease","volume":"1563","author":"Kachroo","year":"2014","journal-title":"Brain Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s41999-018-0055-1","article-title":"Association between allopurinol use and Parkinson\u2019s disease in older adults","volume":"9","author":"Lai","year":"2018","journal-title":"Eur. Geriatr. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9613090","DOI":"10.1155\/2019\/9613090","article-title":"Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases","volume":"2019","author":"Nandi","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1080\/15257770802138558","article-title":"Uric acid: The oxidant-antioxidant paradox","volume":"27","author":"Sautin","year":"2008","journal-title":"Nucleosides Nucleotides Nucleic Acids"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/4\/490\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:30:01Z","timestamp":1760106601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/4\/490"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,18]]},"references-count":26,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["biom14040490"],"URL":"https:\/\/doi.org\/10.3390\/biom14040490","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,18]]}}}