Abstract:
BACKGROUND:Oxidative stress and inflammation are known to play central roles in the development of diabetic nephropathy (DN). Febuxostat is a novel non-purine xanthine oxidase (XO)-specific inhibitor developed to treat hyperuricemia. In this study, we investigated whether febuxostat could ameliorate DN via renoprotective mechanisms such as alleviation of oxidative stress and anti-inflammatory actions. METHODS:Male Sprague-Dawley rats were divided into three groups: a normal group, a diabetes group (DM group), and a febuxostat-treated diabetes group (DM+Fx group). We administered 5 mg/kg of febuxostat to experimental rats for 7 weeks and evaluated clinical and biochemical parameters and XO and xanthine dehydrogenase (XDH) activity in hepatic tissue. The degree of oxidative stress and extent of inflammation were evaluated from urine samples and renal tissue collected from each group. RESULTS:Diabetic rats (DM and DM+Fx groups) had higher blood glucose and kidney weight relative to body weight than normal rats. Albuminuria was significantly reduced in febuxostat-treated diabetic rats compared with untreated diabetic rats. Quantitative analysis showed that hepatic XO and XDH activities were higher in the DM groups, but decreased after treatment with febuxostat. Urinary 8-OHdG concentrations and renal cortical nitrotyrosine also indicated reduced oxidative stress in the DM+Fx group relative to the DM group. The number of ED-1-stained cells in the glomerulus and tubule of diabetic renal tissue decreased in febuxostat-treated diabetic rats relative to that of non-treated diabetic rats. Diabetic rats also expressed higher transcript levels of inflammatory genes (E-selectin and VCAM-1), an inflammation-induced enzyme (COX-2), and inflammatory mediators (ED-1 and NF-κB) than control rats; expression of these genes was significantly reduced by treatment with febuxostat. CONCLUSIONS:Febuxostat prevents diabetic renal injury such as albuminuria. This renoprotective effect appears to be due to attenuation of the inflammatory and oxidative effects of diabetes-induced renal damage through inhibition of XO and XDH activities.
journal_name
Am J Nephroljournal_title
American journal of nephrologyauthors
Lee HJ,Jeong KH,Kim YG,Moon JY,Lee SH,Ihm CG,Sung JY,Lee TWdoi
10.1159/000363421subject
Has Abstractpub_date
2014-01-01 00:00:00pages
56-63issue
1eissn
0250-8095issn
1421-9670pii
000363421journal_volume
40pub_type
杂志文章abstract::The use of Dacron cuff double-lumen permanent catheters for hemodialysis has become more common in the dialysis unit as patients await for creation or maturation of a permanent hemoaccess for various reasons. Placement of these catheters is often done by surgeons. Nephrologists skilled in the placement of temporary ce...
journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000013425
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abstract:UNLABELLED:Although it is anticipated that most patients with renal insufficiency will progress towards end-stage renal disease (ESRD) there have been few population-based studies to validate this assumption. We examined serial creatinines from 3,874 anonymous patients at an urban VA medical center who had a baseline c...
journal_title:American journal of nephrology
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doi:10.1159/000046280
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journal_title:American journal of nephrology
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journal_title:American journal of nephrology
pub_type: 临床试验,杂志文章
doi:10.1159/000108358
更新日期:2007-01-01 00:00:00
abstract::We assessed blood volume (BV) in 20 edematous patients with nephrotic syndrome and in 32 subjects without renal or other disease liable to induce BV variation. Two methods were chosen, one using 131I-albumin and the other 51Cr red blood cells. Among the 20 patients, 11 presented minimal-change lesions, and 9 had histo...
journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000167967
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abstract::Clinical and pathologic findings are described in 14 patients whose main abnormality was an excessively thin glomerular basement membrane (GBM). The subjects were aged 11-51 years, the majority males: most were referred because of hematuria, but proteinuria was the main problem in 2, while hypertension or renal functi...
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pub_type: 杂志文章
doi:10.1159/000166914
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abstract::We report the case of a 42-year-old woman with autosomal dominant polycystic kidney disease complicated by primary aldosteronism. She had a history of hypertension for 12 years and was found to have hypokalemia and polycystic renal and hepatic disease. Endocrinological tests revealed hyporeninemia and hyperaldosterone...
journal_title:American journal of nephrology
pub_type: 杂志文章,评审
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journal_title:American journal of nephrology
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journal_title:American journal of nephrology
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journal_title:American journal of nephrology
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000329081
更新日期:2011-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000487198
更新日期:2018-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000327820
更新日期:2011-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000492623
更新日期:2018-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000476076
更新日期:2017-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000510771
更新日期:2020-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000437171
更新日期:2015-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000013391
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000485845
更新日期:2018-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章
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journal_title:American journal of nephrology
pub_type: 杂志文章
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journal_title:American journal of nephrology
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更新日期:2015-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000013516
更新日期:1999-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000309756
更新日期:2010-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000166815
更新日期:1984-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章,meta分析,评审
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更新日期:2014-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000167335
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journal_title:American journal of nephrology
pub_type: 杂志文章
doi:10.1159/000168891
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journal_title:American journal of nephrology
pub_type: 杂志文章,评审
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更新日期:2009-01-01 00:00:00
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journal_title:American journal of nephrology
pub_type: 杂志文章,随机对照试验
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