Journal of Bioequivalence & Bioavailability

Anti-fi brotic actions of suramin: Novel uses of an old drug

International Conference and Exhibiton on Pharmaceutical Regulatory Affairs

6-7 September 2011 Baltimore, USA

Shougang Zhuang

Scientific Tracks Abstracts: JBB

Abstract:

C hronic kidney disease (CKD) is the result of various insults to the kidney, aff ecting approximately 10% of the normal population. Current drug discovery eff orts for fi ghting renal fi brosis are largely focused on compounds that are specifi c for a particular receptor or protein kinase. Given that renal fi brogenesis is associated with increased production of multiple cytokines/growth factors and subsequent activation of their receptors and signalings pathways, it is expected that inhibitors with broad specifi city might off er improved therepautic benefi t in fi brotic diseases of the kidney. On this basis, we assessed the eff ect of suramin, an FDA approved drug for treating selected malignancies through its inhibitory eff ect on activation of multiple growth factor/cytokine receptors, on the activation of renal interstitial fi broblasts and the development/progression of renal fi brosis in animal models of chronic kidney injury. In a model of obstructive nephropathy induced by uni lateral ureteral obstruction (UUO), administration of suramin immediately aft er injury prevented the onset of renal fi brosis as evidenced by suppression of  -smooth muscle actin (  -SMA) and type 1 collagen expression and reduction of extracellular matrix protein deposition. Delayed administration of suramin at day 3 of ureteral obstruction also inhibited the progression of tubulointerstial fi brosis. In a rat model of remnant kidney disease, suramin prevented progressive re nal injury as demonstrated by inhibiting the rise of 24 hour-proteinuria and serum creatinine, preserving renal tissue architecture and preventing glomerular and tubulointerstitial damage. UUO injury or renal ablation induced phosphorylation of epidermal growth factor receptor, platelet derived growth factor receptor, and several signaling pathways associated renal fi brogenesis. Treatment with suramin blocked phosphorylation of all these molecules in the injured kidney. Moreover, suramin repressed expression of multiple cytokines including TGF-beta1 and decreased leukocyte infi ltration to the interstitium. Th ese fi ndings indicate that suramin is a potent anti-fi brotic agent and may have therapeutic potential in treating patients with CKD.

Biography :

Shougang Zhuang, MD, PhD, is an Associate Professor of Medicine at Brown University School of Medicine, Director of Kidney Research at Rhode Island Hospital, Chief of Nephrology at Shanghai East Hospital, Tongji University School of Medicine. His research is focused on the pathophysiology and drug discovery in acute kidney injury and chronic kidney disease. He has published 55 articles in peer-reviewed journals and serving on the Open Pathology Journal editorial broard.