Peritoneal fibrosis is one of the most serious complications in patients with peritoneal dialysis (PD) and is associated with the loss of peritoneal membrane ultrafiltration function. In this study, we investigated whether suramin, an inhibitor that blocks multiple growth factors by binding to their receptors, would prevent development of peritoneal fibrosis in a rat model. Rats were given a daily intraperitoneal injection of chlorhexidine gluconate (CG) for 3 weeks to induce peritoneal fibrosis. Administration of suramin at 5, 10, and 20 mg/kg dose-dependently attenuated peritoneal membrane thickening and expression of collagen I, fibronectin, and α-smooth muscle actin. Increased expression of transforming growth factor-β1 (TGF-β1) and phosphorylation of Smad3 was detected in fibrotic peritoneum and inhibited by suramin treatment. Suramin was also effective in blocking CG-induced phosphorylation of inhibitor of κB (IκB) and nuclear factor (NF)-κBp65, expression of several inflammatory cytokines, and infiltration of macrophages in the peritoneum. Moreover, suramin suppressed angiogenesis and expression of vascular endothelial growth factor, a molecule associated with angiogenesis in the injured peritoneum. Therefore, our results indicate that suramin treatment can effectively alleviate the development of peritoneal fibrosis by suppression of TGF-β1 signaling, inflammation, and angiogenesis, and suggest that suramin may have therapeutic potential for prevention of peritoneal fibrosis in PD patients.
Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.