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http://purl.uniprot.org/citations/22350467http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22350467http://www.w3.org/2000/01/rdf-schema#comment"

Background

Renal interstitial fibrosis is the common pathway in progressive renal diseases, where oxidative stress promotes inflammation and macrophage infiltration. Febuxostat is a novel nonpurine xanthine oxidase (XO)-specific inhibitor for treating hyperuricemia. While some reports suggest a relationship between hyperuricemia and chronic kidney disease (CKD), the renoprotective mechanism of an XO inhibitor in CKD remains unknown. Recent reports have focused on XO as a source of oxidative stress.

Methods

Here, we investigate the potential of febuxostat to reduce fibrogenic and inflammatory responses in an established interstitial fibrosis model-unilateral ureteric obstruction (UUO). Male Sprague-Dawley rats were divided into three groups: sham-operated group, vehicle-treated UUO group, and febuxostat-treated UUO group.

Results

Treatment with febuxostat diminished XO activity in obstructed kidneys, and suppressed nitrotyrosine, a marker of oxidative stress. Consequently, febuxostat inhibited early proinflammatory cytokine expression, followed by a reduction of interstitial macrophage infiltration. In addition, febuxostat suppressed transforming growth factor-β messenger RNA expression, thereby ameliorating smooth muscle alpha actin and type I collagen expression.

Conclusion

Our results provide evidence for the renoprotective action of febuxostat against the formation of interstitial fibrosis. A decrease in macrophage infiltration and interstitial fibrosis, along with a decrease of the oxidative stress marker, strongly suggests the existence of a causal relationship between them. Febuxostat may have therapeutic value in slowing or preventing interstitial fibrosis in patients with CKD."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.org/dc/terms/identifier"doi:10.1007/s10157-012-0609-3"xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/author"Inoue K."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/author"Ueda Y."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/author"Omori H."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/author"Matsui I."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/author"Moriyama T."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/author"Yamamoto R."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/author"Kawada N."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/author"Isaka Y."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/author"Rakugi H."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/author"Takabatake Y."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/author"Kaimori J."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/name"Clin Exp Nephrol"xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/pages"549-556"xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/title"Use of xanthine oxidase inhibitor febuxostat inhibits renal interstitial inflammation and fibrosis in unilateral ureteral obstructive nephropathy."xsd:string
http://purl.uniprot.org/citations/22350467http://purl.uniprot.org/core/volume"16"xsd:string
http://purl.uniprot.org/citations/22350467http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22350467
http://purl.uniprot.org/citations/22350467http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22350467
http://purl.uniprot.org/uniprot/#_A0A8I5Y0Y5-mappedCitation-22350467http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22350467
http://purl.uniprot.org/uniprot/#_A0A8I5ZPE7-mappedCitation-22350467http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22350467
http://purl.uniprot.org/uniprot/#_F1LQS6-mappedCitation-22350467http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22350467
http://purl.uniprot.org/uniprot/#_P22985-mappedCitation-22350467http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22350467
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