Peritoneal fibrosis is one of serious complications in patients with peritoneal dialysis (PD), and associated with the loss of peritoneal membrane ultrafiltration function. In this study, we investigated whether suramin, an inhibitor that blocks multiple growth factors with their receptors, would prevent development of peritoneal fibrosis in a rat model. Rats were given a daily intraperitoneal injection of chlorhexidine gluconate for three weeks to induce peritoneal fibrosis. Administration of suramin at 5, 10, 20 mg/kg dose-dependently attenuated peritoneal membrane thickening and expression of collagen I, fibronectin and α-smooth muscle actin. Increased expression of TGF-β1 and phosphorylation of Smad3 were detected in fibrotic peritoneum, and inhibited by suramin treatment. Suramin was also effective in blocking chlorhexidine gluconate-induced phosphorylation of IκB and NF-κB p65, expression of several inflammatory cytokines and infiltration of macrophages in the peritoneum. Moreover, suramin suppressed 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, angiogenesis and suggest that suramin may have therapeutic potential for prevention of peritoneal fibrosis in PD patients.
- The American Society for Pharmacology and Experimental Therapeutics