期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 750, 期 -, 页码 1-7出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2015.01.020
关键词
Unilateral ureteral obstruction; Caffeamide; Renal fibrosis; Obstructive nephropathy
资金
- National Science Council Taiwan Grant [102-2325-B-002-095-B4]
- Ministry of Science and Technology, Taiwan [103-2325-B-002-020]
Unilateral ureteral obstruction (UUO) is an established animal model used to study renal nephropathy. Caffeic acid phenethyl ester, a natural phenolic compound, possesses antifibrotic, anti-inflammation and anti-oxidative stress effects; however, rapid decomposition by esterases substantially decreases its bioavailability. The goal of this study was to investigate the beneficial effects of KS370G, a synthetic caffeamide derivative, on UUO-induced renal injury. Following the UUO, KS370G (10 mg/kg) was administered by oral gavage once a day. Renal injury was analyzed at 14 clays post-operation. Our results show that KS370G significantly attenuated collagen deposition in the obstructed kidney and inhibited UUO-induced renal fibrosis markers expression, including fibronectin, type l collagen, vimentin, and a-smooth muscle actin (alpha-SEMA). KS370G significantly lowered the expression of renal inflammatory chemokines/adhesion molecules and monocyte cells marker (MCP-1, VCAM-1, ICAM-1 and CD11b). KS370G also reduced renal malondialdehyde levels and reversed the expression of renal antioxidant enzymes (SOD and catalase) after UUO. Furthermore, K5370G significantly inhibited UUo-induced elevated plasma Angll and TGE-beta(1) levels, TGF-beta(1) protein expression and Smad3 phosphorylation. These findings demonstrate that KS370G reduces renal obstructive nephropathy by possibly inhibiting Angll, TGF-beta and Smad3 signaling pathways. (C) 2015 Elsevier B.V. All rights reserved.
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