Attenuation of renal fibrosis by curcumin in rat obstructive nephropathy

Abstract

Objectives To test whether curcumin has a protective action against interstitial inflammation and the development of renal fibrosis in obstructive nephropathy. We also tested whether inhibition of nuclear factor kappa-B (NF-κB) and activator protein-1 (AP-1) by curcumin is involved in these mechanisms. Methods Adult male rats underwent unilateral ureteral obstruction. The rats were treated with curcumin (200 mg/kg/day or 800 mg/kg/day), NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC; 200 mg/kg/day), or vehicle by gavage. Sham-operated rats served as controls. Seven days after unilateral ureteral obstruction, the activity of NF-κB and AP-1 was examined by electrophoretic mobility shift assay using nuclear protein extracts from the renal cortex. Gene expression of chemokines and pro-fibrotic molecules was determined by real-time reverse transcriptase-polymerase chain reaction. Macrophage infiltration and collagen III accumulation in the cortical interstitium was examined immunohistochemically. Results Both curcumin and PDTC significantly attenuated interstitial macrophage influx and renal fibrosis. Ureteral occlusion activated both NF-κB and AP-1-DNA binding. Curcumin and PDTC significantly inhibited NF-κB activity, but not AP-1. Gene expression of chemokines and pro-fibrotic molecules was upregulated in unilateral ureteral obstruction that was attenuated by either curcumin or PDTC. Conclusions Curcumin protected against the renal interstitial inflammation and fibrosis elicited by ureteral occlusion. Inhibition of the NF-κB-dependent pathway is at least in part involved in the mechanisms, but AP-1 inhibition is unlikely to be involved in the beneficial effects of curcumin.