التفاصيل البيبلوغرافية
| العنوان: |
Use of xanthine oxidase inhibitor febuxostat inhibits renal interstitial inflammation and fibrosis in unilateral ureteral obstructive nephropathy. |
| المؤلفون: |
Omori, Hiroki, Kawada, Noritaka, Inoue, Kazunori, Ueda, Yoshiyasu, Yamamoto, Ryohei, Matsui, Isao, Kaimori, Jyunya, Takabatake, Yoshitsugu, Moriyama, Toshiki, Isaka, Yoshitaka, Rakugi, Hiromi |
| المصدر: |
Clinical & Experimental Nephrology; Aug2012, Vol. 16 Issue 4, p549-556, 8p |
| مصطلحات موضوعية: |
XANTHINE oxidase, INFLAMMATION, FIBROSIS, KIDNEY diseases, HYPERURICEMIA, MACROPHAGES, OXIDATIVE stress, CYTOKINES |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
