KS370G, a caffeamide derivative, attenuates unilateral ureteral obstruction-induced renal fibrosis by the reduction of inflammation and oxidative stress in mice.

Abstract

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 (10mg/kg) was administered by oral gavage once a day. Renal injury was analyzed at 14 days 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 I collagen, vimentin, and α-smooth muscle actin (α-SMA). 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, KS370G significantly inhibited UUO-induced elevated plasma AngII and TGF-β1 levels, TGF-β1 protein expression and Smad3 phosphorylation. These findings demonstrate that KS370G reduces renal obstructive nephropathy by possibly inhibiting AngII, TGF-β and Smad3 signaling pathways.

• Authors: Sung-Ting Chuang, Yueh-Hsiung Kuo, Ming-Jai Su
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 750 Pg. 1-7 (Mar 05 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 25620133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• Caffeic Acids
• Cell Adhesion Molecules
• Chemokines
• Collagen Type I
• Fibronectins
• KS370G
• Smad3 Protein
• Transforming Growth Factor beta1
• Angiotensin II
• Catalase
• Superoxide Dismutase

Topics

• Angiotensin II (metabolism)
• Animals
• Biomarkers (metabolism)
• Caffeic Acids (pharmacology)
• Catalase (metabolism)
• Cell Adhesion Molecules (metabolism)
• Chemokines (metabolism)
• Collagen Type I (metabolism)
• Cytoprotection (drug effects)
• Fibronectins (metabolism)
• Fibrosis
• Gene Expression Regulation (drug effects)
• Inflammation (metabolism)
• Kidney (drug effects, pathology)
• Lipid Peroxidation (drug effects)
• Male
• Mice
• Oxidative Stress (drug effects)
• Smad3 Protein (metabolism)
• Superoxide Dismutase (metabolism)
• Transforming Growth Factor beta1 (metabolism)
• Ureteral Obstruction (metabolism, pathology)