{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:54:05Z","timestamp":1787500445608,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2019,9,21]],"date-time":"2019-09-21T00:00:00Z","timestamp":1569024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Scientific Research (C)","award":["16K09791"],"award-info":[{"award-number":["16K09791"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hyperuricemia has been recognized as a risk factor for insulin resistance as well as one of the factors leading to diabetic kidney disease (DKD). Since DKD is the most common cause of end-stage renal disease, we investigated whether febuxostat, a xanthine oxidase (XO) inhibitor, exerts a protective effect against the development of DKD. We used KK-Ay mice, an established obese diabetic rodent model. Eight-week-old KK-Ay mice were provided drinking water with or without febuxostat (15 \u03bcg\/mL) for 12 weeks and then subjected to experimentation. Urine albumin secretion and degrees of glomerular injury judged by microscopic observations were markedly higher in KK-Ay than in control lean mice. These elevations were significantly normalized by febuxostat treatment. On the other hand, body weights and high serum glucose concentrations and glycated albumin levels of KK-Ay mice were not affected by febuxostat treatment, despite glucose tolerance and insulin tolerance tests having revealed febuxostat significantly improved insulin sensitivity and glucose tolerance. Interestingly, the IL-1\u03b2, IL-6, MCP-1, and ICAM-1 mRNA levels, which were increased in KK-Ay mouse kidneys as compared with normal controls, were suppressed by febuxostat administration. These data indicate a protective effect of XO inhibitors against the development of DKD, and the underlying mechanism likely involves inflammation suppression which is independent of hyperglycemia amelioration.<\/jats:p>","DOI":"10.3390\/ijms20194680","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T03:26:32Z","timestamp":1569209192000},"page":"4680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Xanthine Oxidase Inhibitor Febuxostat Exerts an Anti-Inflammatory Action and Protects against Diabetic Nephropathy Development in KK-Ay Obese Diabetic Mice"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-5300","authenticated-orcid":false,"given":"Yu","family":"Mizuno","sequence":"first","affiliation":[{"name":"Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yamamotoya","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Nakatsu","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuka","family":"Matsunaga","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan"},{"name":"Center for Translational Research in Infection &amp; Inflammation, School of Medicine, Tulane University, 6823 St. Charles Avenue, New Orleans, LA 70118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masa-Ki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Sakoda","sequence":"additional","affiliation":[{"name":"Division of Neurology, Respirology, Endocrinology, and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Fujishiro","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiraku","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Metabolism, The Institute for Adult Diseases, Asahi Life Foundation, 2-2-6, Nihonbashi Bakurocho, Chuo-ku, Tokyo 103-0002, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose City, Tokyo 204-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4098-2726","authenticated-orcid":false,"given":"Kenichi","family":"Morii","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Masaki","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoichiro","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1385-7487","authenticated-orcid":false,"given":"Akifumi","family":"Kushiyama","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose City, Tokyo 204-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Matoba, K., Takeda, Y., Nagai, Y., Kawanami, D., Utsunomiya, K., and Nishimura, R. 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