RT Journal Article
SR Electronic
T1 Suramin inhibits the development and progression of peritoneal fibrosis
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.114.215228
DO 10.1124/jpet.114.215228
A1 Chongxiang Xiong
A1 Lu Fang
A1 Na Liu
A1 Shougang Zhuang
A1 Haidong Yan
YR 2014
UL http://jpet.aspetjournals.org/content/early/2014/08/28/jpet.114.215228.abstract
AB 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.