Attenuation of renal fibrosis by curcumin in rat obstructive nephropathy.
OBJECTIVE
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-kappaB) 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-kappaB 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-kappaB 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-kappaB and AP-1-DNA binding. Curcumin and PDTC significantly inhibited NF-kappaB 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-kappaB-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.
Kuwabara
Nobuyuki
N
Department of Urology, Osaka City University Medical School, Osaka, Japan.
Tamada
Satoshi
S
Iwai
Tomoaki
T
Teramoto
Kae
K
Kaneda
Noriko
N
Yukimura
Tokihito
T
Nakatani
Tatsuya
T
Miura
Katsuyuki
K
D000818:Animals; D003474:Curcumin / Q000627:therapeutic use*; D005355:Fibrosis / Q000150:complications / Q000517:prevention & control; D007668:Kidney / Q000473:pathology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D014517:Ureteral Obstruction / Q000209:etiology / Q000517:prevention & control*
D016328:NF-kappa B; D018808:Transcription Factor AP-1; D003474:Curcumin