ks370g and Ureteral-Obstruction

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.

Topics: Angiotensin II; Animals; Biomarkers; Caffeic Acids; Catalase; Cell Adhesion Molecules; Chemokines; Collagen Type I; Cytoprotection; Fibronectins; Fibrosis; Gene Expression Regulation; Inflammation; Kidney; Lipid Peroxidation; Male; Mice; Oxidative Stress; Smad3 Protein; Superoxide Dismutase; Transforming Growth Factor beta1; Ureteral Obstruction